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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT00098657
Registration number
NCT00098657
Ethics application status
Date submitted
3/06/2004
Date registered
4/06/2004
Date last updated
26/01/2010
Titles & IDs
Public title
SU011248 Versus Interferon-Alfa As First-Line Systemic Therapy For Patients With Metastatic Renal Cell Carcinoma
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Scientific title
A Phase 3, Randomized Study Of SU011248 Versus Interferon-Alfa As First-Line Systemic Therapy For Patients With Metastatic Renal Cell Carcinoma
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Secondary ID [1]
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A6181034
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Renal Cell
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Chronic Myelogenous Leukemia
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Myeloid Leukemia, Chronic, Accelerated Phase
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0
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Leukemia, Lymphoblastic, Acute, Philadelphia-Positive
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0
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Leukemia, Myeloid, Chronic Phase
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0
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Leukemia, Lymphoblastic, Acute, Philadelphia-positive
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0
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Condition category
Condition code
Cancer
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0
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Non melanoma skin cancer
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Cancer
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0
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0
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Kidney
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Cancer
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Leukaemia - Acute leukaemia
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Cancer
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Leukaemia - Chronic leukaemia
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Cancer
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Children's - Leukaemia & Lymphoma
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Blood
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Other blood disorders
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Cancer
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Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
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Cancer
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0
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Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
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Human Genetics and Inherited Disorders
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0
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Other human genetics and inherited disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Interferon-alfa
Treatment: Drugs - SU011248
Treatment: Drugs - Dasatinib
Treatment: Drugs - Dasatinib
Treatment: Drugs - Temsirolimus (CCI-779)
Treatment: Drugs - Temsirolimus (CCI-779)
Treatment: Drugs - Imatinib mesylate
Treatment: Drugs - dasatinib
Treatment: Drugs - Investigator's choice
Treatment: Drugs - dasatinib
Treatment: Drugs - Dasatinib
Treatment: Drugs - Dasatinib
Active comparator: 2 -
Experimental: 1 -
Experimental: 1 -
Experimental: 1 -
Experimental: A -
Experimental: B -
Active comparator: C -
Experimental: dasatinib Twice a Day (BID) - 70 mg dasatinib twice a day (BID)
Experimental: Imatinib 400 mg - Oral dose of 400mg Imatinib once daily. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
Experimental: dasatinib Once a Day (QD) - 140 mg dasatinib once a day (QD)
Experimental: imatinib 800 mg - Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
Experimental: 1 -
Treatment: Drugs: Interferon-alfa
3 MIU first week, 6 MIU second week, and 9 MIU thereafter three times a week (non-consecutive days) until progression or unacceptable toxicity
Treatment: Drugs: SU011248
50 mg orally daily for 4 weeks and 2 weeks off treatment until progression or unacceptable toxicity
Treatment: Drugs: Dasatinib
Tablets, Oral, 70 mg, twice daily, until disease progression or intolerable toxicity, switch to the roll-over study or study closure
Treatment: Drugs: Dasatinib
Tablets, Oral, 70 mg, twice daily, Until disease progression or intolerable toxicity, switch to the roll-over study or study closure.
Treatment: Drugs: Temsirolimus (CCI-779)
Temsirolimus 175 mg IV once a week for 3 weeks; followed by 75 mg IV once a week
Treatment: Drugs: Temsirolimus (CCI-779)
Temsirolimus 175 mg IV once a week for 3 weeks; followed by 25 mg IV once a week
Treatment: Drugs: Imatinib mesylate
Imatinib is packaged in bottles as 100mg and 400mg tablets
Treatment: Drugs: dasatinib
Tablets, Oral, 70 mg BID, indefinitely, survival study
Treatment: Drugs: Investigator's choice
Any of the following single agent treatments:
1. Fludarabine 25 mg/m2 IV over 30 minutes daily for 5 consecutive days, every 28 days or oral administration, as appropriate.
2. Chlorambucil 0.1 (0.1-0.2) mg/kg PO daily for 3 to 6 weeks as required OR 0.4 (0.3 0.8) mg/kg PO every 21 to 28 days
3. Gemcitabine 1 gm/m2 IV over 30 minutes on days 1, 8 and 15 every 28 days or day 1 and day 8 every 21 days
4. Cyclophosphamide 300 (200-450) mg/m2 PO daily for 5 consecutive days every 21 to 28 days, OR 600 (400-1200) mg/m2 IV every 21 to 28 days
5. Cladribine 5 mg/m2 IV daily for 5 consecutive days, every 28 days for 2-6 cycles depending on response,
6. Etoposide 50 (50-150) mg/m2 IV daily for 3-5 days every 21 to 28 days OR 100 (50 300) mg/m2 PO daily for 3-5 days every 21 to 28 days
7. Prednisone 40 (20-60) mg/m2 PO daily or every other day
8. Dexamethasone 20(20-40) mg PO/IV daily for 5 consecutive days, every 14 - 28 day
Treatment: Drugs: dasatinib
Tablets, Oral, 140 mg QD, indefinitely, survival study
Treatment: Drugs: Dasatinib
Tablets; oral; 70 mg BID, depending on response
Treatment: Drugs: Dasatinib
Tablets, Oral, 70 mg, twice daily, Until disease progression or untolerable toxicity, switch to the roll-over study or study closure
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Progression-Free Survival (PFS), Core Radiology Assessment
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Assessment method [1]
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Progression-free survival (PFS) = time from randomization to first documentation of objective tumor progression or to death due to any cause, whichever occured first. If tumor progression data included more than 1 date, the first date was used. PFS = first event date minus the date of randomization + 1. On study included treatment plus 28-day follow-up periods.
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Timepoint [1]
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Day 28 of each 6-week cycle: duration of treatment phase
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Primary outcome [2]
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Progression-Free Survival (PFS), Investigator's Assessment
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Assessment method [2]
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Progression-free survival = time from randomization to first documentation of objective tumor progression or to death due to any cause, whichever occured first. PFS = first event date minus the date of randomization + 1). On study included treatment plus 28-day follow-up periods.
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Timepoint [2]
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Day 28 of each 6-week cycle: duration of treatment phase
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Primary outcome [3]
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Major and Overall Hematologic Response (MaHR and OHR)
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Assessment method [3]
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MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). OHR=best confirmed response of MaHR or minor hematologic response (MiHR). Confirmed hematologic response=response confirmed =4 weeks after first documented event with no concomitant use of anagrelide or hydroxyurea. Maintaining a response=no 2 consecutive records of nonresponse at assessment. Criteria for CHR and NEL specified in Outcome Measure 2 and criteria for MiHR in Outcome Measure 4.
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Timepoint [3]
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Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment
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Primary outcome [4]
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Major and Overall Hematologic Response (MaHR and OHR)
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Assessment method [4]
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MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR are specified in Outcome Measure 2. OHR=best confirmed response of MaHR or minor HR (MiHR). MiHR= \<15% blasts in bone marrow and \<15% blasts in peripheral blood (PB); \<30% blasts + promyelocytes in bone marrow and \<30% blasts + promyelocytes in PB; \<20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response=response confirmed =4 weeks after first documented event with no concomitant use of anagrelide or hydroxyurea.
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Timepoint [4]
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Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment
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Primary outcome [5]
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Progression-Free Survival (PFS)
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Assessment method [5]
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The period from randomization until disease progression, death or date of last contact.
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Timepoint [5]
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Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)
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Primary outcome [6]
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Percentage of Participants With Major Molecular Response (MMR) Rates at 12 Months
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Assessment method [6]
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MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region \[Bcr\] gene and Abelson proto-oncogene \[Abl\] genes) transcript ratio =0.1% (= 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction \[RT-PCR\] (performed centrally).
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Timepoint [6]
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12 months
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Primary outcome [7]
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Percent of Participants With Major Hematologic Response (MaHR) With 6 Months of Follow-up From Date of Last Enrollment - Randomized Population
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Assessment method [7]
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MaHR defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) = upper limit of normal (ULN); absolute neutrophil count (ANC) = 1,000/mm\^3; platelets = 100,000/mm\^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts = 5%; \<5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets = 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percentage: number of participants with MaHR/number of randomized participants.
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Timepoint [7]
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Randomization up to 6 months
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Primary outcome [8]
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Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR)
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Assessment method [8]
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Cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases plus Partial Cytogenetic Response (PCyR)-1% to 35% Ph+ metaphases.
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Timepoint [8]
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2 years
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Primary outcome [9]
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Major and overall hematologic response rates
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Assessment method [9]
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0
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Timepoint [9]
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throughout the study
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Secondary outcome [1]
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Objective Response, Core Radiology Assessment
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Assessment method [1]
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Objective response (OR) = the number of patients with confirmed complete response (CR) and confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, relative to all randomized patients. CR was defined as the disappearance of all target lesions. PR was defined as a = 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Confirmed responses (CR or PR) = those that persisted on repeat imaging study \>= 4 weeks after initial documentation of response.
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Timepoint [1]
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Day 28 of each 6-week cycle: duration of treatment phase
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Secondary outcome [2]
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Objective Response, Investigator's Assessment
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Assessment method [2]
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Objective response (OR) = the number of patients with confirmed complete response (CR) and confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, relative to all randomized patients. CR was defined as the disappearance of all target lesions. PR was defined as a = 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Confirmed responses = those that persist on repeat imaging study \>= 4 weeks after initial documentation of response.
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Timepoint [2]
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Day 28 of each 6-week cycle: duration of treatment phase
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Secondary outcome [3]
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Overall Survival (OS)
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Assessment method [3]
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Overall survival (OS) = time from date of randomization to date of death due to any cause. For patients not expiring, survival time was censored at the last date they were known to be alive. Patients lacking data beyond randomization had their survival times censored at the date of randomization with a duration of 1 day.
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Timepoint [3]
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Clinic visit or telephone contact every 2 months until death
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Secondary outcome [4]
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Time to Tumor Progression (TTP), Core Radiology Assessment
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Assessment method [4]
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TTP = time from randomization to first documentation of objective tumor progression. TTP data were censored on the day following the date of last on treatment (including 28 day follow-up period) tumor assessment documenting absence of progressive disease for subjects who did not have objective tumor progression while on treatment or who were given anti-tumor treatment other than study treatment prior to documentation of objective tumor progression. Subjects with no tumor assessments after randomization had TTP censored on the date of randomization with a duration of 1 day.
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Timepoint [4]
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Randomization to first documentation of tumor progression: duration of treatment phase
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Secondary outcome [5]
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Time to Tumor Progression (TTP), Investigator's Assessment
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Assessment method [5]
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TTP = time from randomization to first documentation of objective tumor progression. TTP data were censored on the day following the date of last on treatment (including 28 day follow-up period) tumor assessment documenting absence of progressive disease for subjects who did not have objective tumor progression while on treatment or who were given anti-tumor treatment other than the study treatment prior to documentation of objective tumor progression. Subjects with no tumor assessments after randomization had TTP censored on the date of randomization with a duration of 1 day.
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Timepoint [5]
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0
Randomization to first documentation of tumor progression: duration of treatment phase
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Secondary outcome [6]
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Duration of Response (DR), Core Radiology Assessement
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Assessment method [6]
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Duration of response (DR) = time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause. DR data were censored on the day following the date of the last on treatment (including 28 day follow-up period) tumor assessment documenting absence of progressive disease for subjects without objective tumor progression who did not die due to any cause while on treatment or who were given anti-tumor treatment other than study treatment prior to observing tumor progression.
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Timepoint [6]
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Day 28 of each cycle: duraton of treatment phase
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Secondary outcome [7]
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Duration of Response (DR), Investigator's Assessment
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Assessment method [7]
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Duration of response (DR) = time from the first documentation of objective tumor response to the first documentaion of objective tumor progression or to death due to any cause. DR data were censored on the day following the date of the last on treatment (including 28 day follow-up period) tumor assessment documenting absence of progressive disease for subjects without objective tumor progression who did not die due to any cause while on treatment or who were given anti-tumor treatment other than study treatment prior to observing tumor progression.
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Timepoint [7]
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Day 28 of each cycle: duration of treatment phase
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Secondary outcome [8]
0
0
FACT-Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Subscale
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Assessment method [8]
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FACT-Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) subscale of the FKSI to measure advanced kidney cancer disease related symptoms. Includes 9 items: lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria. Each question was answered on a five-point Likert-type scale ranging from 0 (not at all) to 4 (very much). Score = the sum score of the item scores in the subscale; total range: 0 to 36. A score greater than 0 indicates the difference favored sunitinib.
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Timepoint [8]
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Day 1 & 28 of each cycle: duration of treatment phase
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Secondary outcome [9]
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FACT-Kidney Symptom Index (FKSI) Subscale
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Assessment method [9]
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FACT-Kidney Symptom Index (FKSI) subscale designed to be a stand-alone instrument to measure symptoms and quality of life in patients with advanced kidney cancer. Contains 15 questions; some questions overlap with the FACT-G questions. Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Total FKSI score = sum score of the 15 item scores; total range: 0 - 60; 0 (most severe symptoms and concerns) to 60 (no symptoms or concerns).
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Timepoint [9]
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Day 1 & 28 of each cycle: duration of treatment phase
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Secondary outcome [10]
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Functional Assessment of Cancer Therapy-General (FACT-G)
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Assessment method [10]
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Functional Assessment of Cancer Therapy-General (FACT-G): core questionnaire of the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system that has been validated in a variety of cancer populations. 27 questions grouped into 4 domains that measure a patient's physical, functional, social and family, and emotional well-being. Five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = sum score of item scores in the subscale; total range: 0 to 108 with higher score indicating better quality of life.
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Timepoint [10]
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Day 1 & 28 of each cycle: duration of treatment phase
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Secondary outcome [11]
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0
Functional Assessment of Cancer Therapy-General (FACT-G): Physical Well Being (PWB) Subscale
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Assessment method [11]
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Physical well-being (PWB) subscale of the Functional Assessment of Cancer Therapy-General (FACT-G). Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = the sum score of the item scores in the subscale; range: 0 to 28; lower score indicates better physical well-being.
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Timepoint [11]
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Day 1 & 28 of each cycle: duration of treatment phase
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Secondary outcome [12]
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0
Functional Assessment of Cancer Therapy-General (FACT-G): Social/Family Well Being (SWB) Subscale
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Assessment method [12]
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Social/family well-being (SWB)subscale of the Functional Assessment of Cancer Therapy-General (FACT-G). Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = the sum score of the item scores in the subscale; range: 0 to 28; lower score indicates less social/family well-being.
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Timepoint [12]
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0
Day 1 & 28 of each cycle: duration of treatment phase
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Secondary outcome [13]
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0
Functional Assessment of Cancer Therapy-General (FACT-G): Emotional Well Being (EWB) Subscale
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Assessment method [13]
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Emotional well-being (EWB)subscale of the Functional Assessment of Cancer Therapy-General (FACT-G). Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = the sum score of the item scores in the subscale; range: 0 to 24; lower score indicates better emotional well-being.
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Timepoint [13]
0
0
Day 1 & 28 of each cycle: duration of treatment phase
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Secondary outcome [14]
0
0
Functional Assessment of Cancer Therapy-General (FACT-G): Functional Well Being (FWB) Subscale
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Assessment method [14]
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Functional well-being (FWB) subscale of the Functional Assessment of Cancer Therapy-General (FACT-G). Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = the sum score of the item scores in the subscale; range: 0 to 28; higher score indicates greater functional well-being.
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Timepoint [14]
0
0
Day 1 & 28 of each cycle: duration of treatment phase
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Secondary outcome [15]
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0
EuroQoL Five Dimension (EQ-5D) Health State Index
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Assessment method [15]
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EQ-5D Health State Index: a brief, self-administered generic health status instrument. Respondents were asked to describe their current health state on each of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety or depression) on a three-level scale (1=no problem, 2=some problem, and 3=extreme problem). A maximum score of 1 can be derived from these 5 dimensions by score conversion; range: -0.39 (worst health state)to 1.00 (best health state). This descriptive system classifies respondents into one of 243 possible distinct health states (EQ-5D descriptive system).
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Timepoint [15]
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0
Day 1 & 28 of each cycle: duration of treatment phase
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Secondary outcome [16]
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0
Euro-QoL Visual Analog Scale (EQ-VAS)
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Assessment method [16]
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EQ-VAS: overall self-rating rating of the patient's current health state using a 20 cm Visual Analog Scale (EQ-VAS), also called the health state thermometer) is a metric measurement (in 2 mm interval) from the visual analog scale which ranges between 0 (worse imaginable health state) and 100 (best imaginable health state).
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Timepoint [16]
0
0
Day 1 & 28 of each cycle: duration of treatment phase
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Secondary outcome [17]
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0
Plasma Concentrations of Soluble Proteins: Plasma VEGF-A, Plasma VEGF-C, Plasma sVEGFR-3, PLASMA IL-8, and PLASMA bFGF That May be Associated With Tumor Proliferation or Angiogenesis
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Assessment method [17]
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Plasma concentrations of soluble proteins that may be associated with tumor proliferation or angiogenesis collected from a subset of patients were analyzed by enzyme-linked immunosorbent assay (ELISA) analysis. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio = plasma concentration of soluble protein (picograms per milliliter \[pg/ml\]) at timepoint / concentration of soluble protein (pg/ml) at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
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Timepoint [17]
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0
Day 1 & Day 28, Cycle 1 to Cycle 4
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Secondary outcome [18]
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0
Plasma Concentrations of Soluble Proteins: Plasma Basic Fibroblast Growth Factor (bFGF) That May be Associated With Tumor Proliferation or Angiogenesis
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Assessment method [18]
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0
Plasma concentrations of soluble proteins that may be associated with tumor proliferation or angiogenesis collected from a subset of patients were analyzed by enzyme-linked immunosorbent assay (ELISA) analysis. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio = plasma concentration of soluble protein (picograms per milliliter \[pg/ml\]) at timepoint / concentration of soluble protein (pg/ml) at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
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Timepoint [18]
0
0
Day 1 & Day 28, Cycle 1 to Cycle 4
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Secondary outcome [19]
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0
Incremental Cost Effectiveness Ratio (ICER)
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Assessment method [19]
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Incremental cost effectiveness ratio (ICER) of sunitinib compared to IFN-a as first-line treatment for MRCC, defined as the ratio of the incremental cost of treatment over the incremental effectiveness; effectiveness measured as quality adjusted life year (QALY) gain. This objective was not addressed in the clinical study report, but an interim analysis of cost-effectiveness was presented separately. These results were not available for inclusion at the time of this posting.
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Timepoint [19]
0
0
post study measurement
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Secondary outcome [20]
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0
Ctrough Concentrations of SU011248
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Assessment method [20]
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Subject observed Ctrough (trough drug) concentrations of SU011248 per cycle and study day determined by plasma trough samples collected from a subset of patients. Steady-state observed trough concentrations were dose corrected to the starting dose (reference dose) where appropriate. Concentrations below the limits of quantitation (BLQ) were set to 0. Ctrough = minimum (trough) plasma concentration (nanograms per milliliter \[ng/mL\]).
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Timepoint [20]
0
0
Day 28 of Cycle 1 to Cycle 4
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Secondary outcome [21]
0
0
Ctrough Concentrations of Metabolite SU012662
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Assessment method [21]
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Subject observed Ctrough (trough drug) concentrations of active metabolite SU012662 per cycle and study day determined by plasma trough samples collected from a subset of patients. Steady-state observed trough concentrations were dose corrected to the starting dose (reference dose) where appropriate. Concentrations below the limits of quantitation (BLQ) were set to 0. Ctrough = minimum (trough) plasma concentration (nanograms per milliliter \[ng/mL\]).
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Timepoint [21]
0
0
Day 28 of Cycle 1 to Cycle 4
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Secondary outcome [22]
0
0
Ctrough Concentrations of SU011248 and Active Metabolite SU012662
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Assessment method [22]
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Subject observed Ctrough (trough drug) concentrations of total drug (SU011248 and its active metabolite SU012662) per cycle and study day determined by plasma trough samples collected from a subset of patients. Steady-state observed trough concentrations were dose corrected to the starting dose (reference dose) where appropriate. Concentrations below the limits of quantitation (BLQ) were set to 0. Ctrough = minimum (trough) plasma concentration (nanograms per milliliter \[ng/mL\]).
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Timepoint [22]
0
0
Day 28 of Cycle 1 to Cycle 4
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Secondary outcome [23]
0
0
Percentage of Participants Who Achieved MaHR and Did Not Progress at 12 Months (Based on the Kaplan-Meier Estimate of the Duration of Response)
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Assessment method [23]
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0
MaHR=best response of CHR or NEL. CHR=white blood cells =institutional upper limit of normal (iULN); absolute neutrophil count (ANC) =1000/mm3; platelets =100,000/mm3; no blasts/promyelocytes in peripheral blood (PB); bone marrow blasts =5%; \<5% myelocytes+metamyelocytes in PB; PB basophils = iULN; no extramedullary involvement. NEL=WBC =iULN; no blasts/promyelocytes in PB; bone marrow blasts =5%; \<5% myelocytes+metamyelocytes in PB; PB basophils =iULN; no extramedullary involvement; at least 1 of: ANC =500/mm3 \& \<1000/mm3; platelets =20,000/mm3 \& \<100,000/mm3.
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Timepoint [23]
0
0
12 months
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Secondary outcome [24]
0
0
Percentage of Participants Who Achieved MaHR and Did Not Progress at 24 Months in the Imatinib-Resistant Group (Based on the Kaplan-Meier Estimate of the Duration of Response)
Query!
Assessment method [24]
0
0
Percentage of participants in the Imatinib-Resistant Group who achieved MaHR and did not progress at Month 24, based on the Kaplan-Meier estimate of the duration of response. MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR and NEL are specified in Outcome Measure 2.
Query!
Timepoint [24]
0
0
24 months
Query!
Secondary outcome [25]
0
0
Percentage of Participants Who Achieved OHR and Did Not Progress at 12 Months and 24 Months
Query!
Assessment method [25]
0
0
Percentage of participants who achieved OHR and did not progress at specified timepoints, based on the Kaplan-Meier estimate of the duration of response. OHR=best confirmed response of MaHR or MiHR. MaHR criteria in Outcome Measure 2. MiHR= \<15% blasts in bone marrow and \<15% blasts in peripheral blood (PB); \<30% blasts+promyelocytes in bone marrow and \<30% blasts+promyelocytes in PB; \<20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response= confirmed =4 weeks after 1st documented event with no concomitant use of anagrelide or hydroxyurea.
Query!
Timepoint [25]
0
0
12 months, 24 months
Query!
Secondary outcome [26]
0
0
Median Time in Days From First Dosing Date to Date of MaHR
Query!
Assessment method [26]
0
0
MaHR=best response of CHR or NEL. CHR=white blood cells =institutional upper limit of normal (iULN); absolute neutrophil count (ANC) =1000/mm3; platelets =100,000/mm3; no blasts/promyelocytes in peripheral blood (PB); bone marrow blasts =5%; \<5% myelocytes+metamyelocytes in PB; PB basophils = iULN; no extramedullary involvement. NEL=WBC =iULN; no blasts/promyelocytes in PB; bone marrow blasts =5%; \<5% myelocytes+metamyelocytes in PB; PB basophils =iULN; no extramedullary involvement; at least 1 of: ANC =500/mm3 \& \<1000/mm3; platelets =20,000/mm3 \& \<100,000/mm3.
Query!
Timepoint [26]
0
0
Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment
Query!
Secondary outcome [27]
0
0
Time to OHR
Query!
Assessment method [27]
0
0
Median time (in months) from first dosing date to date of OHR. OHR=best confirmed response of MaHR or MiHR. Criteria for MaHR specified in Outcome Measure 2. MiHR= \<15% blasts in bone marrow and \<15% blasts in peripheral blood (PB); \<30% blasts+promyelocytes in bone marrow and \<30% blasts+promyelocytes in PB; \<20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response = response confirmed =4 weeks after 1st documented event with no concomitant use of anagrelide or hydroxyurea.
Query!
Timepoint [27]
0
0
Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment
Query!
Secondary outcome [28]
0
0
Best Cytogenetic Response
Query!
Assessment method [28]
0
0
Number of participants with complete, partial, minor, minimal, or no cytogenetic response. Determination of cytogenetic response based on the prevalence (percentage) of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase in a bone marrow sample (aspirates/biopsies).
Query!
Timepoint [28]
0
0
Baseline (within 4 weeks of therapy start); Every month for Cycles 1-3; Every 12 weeks for Cycles 4+; end of treatment
Query!
Secondary outcome [29]
0
0
Best Confirmed Hematologic Response
Query!
Assessment method [29]
0
0
Number of participants with confirmed complete hematologic response (CHR) or No Evidence of Leukemia (NEL), minor hematologic response (MiHR), or no hematologic response. Confirmed hematologic response=response that is confirmed after at least 4 weeks with no concomitant use of anagrelide or hydroxyurea use during this interval. Criteria for CHR and NEL are specified in Outcome Measure 2; criteria for MiHR are specified in Outcome Measure 4.
Query!
Timepoint [29]
0
0
Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment
Query!
Secondary outcome [30]
0
0
Number of Participants Who Achieved a Major Molecular Response (MMR) During Treatment Period
Query!
Assessment method [30]
0
0
Number of participants who achieved an MMR at any time during the treatment period. MMR was calculated by measuring BCR-ABL transcripts in blood during treatment using quantitative reverse transcription-polymerase chain reaction (RT-PCR). BCR-ABL=the fused gene found in subjects with this type of Chronic Myeloid Leukemia (CML).
Query!
Timepoint [30]
0
0
Baseline, every 12 weeks throughout study (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).
Query!
Secondary outcome [31]
0
0
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations
Query!
Assessment method [31]
0
0
Major hematologic and cytogenetic responses (MaHR and MCyR) to dasatinib in subjects with mutations at baseline, including imatinib-resistant mutations (IRM) and specific BCR-ABL mutations (SBAM). BCR-ABL=the fused gene found in subjects with this type of CML. Criteria for MaHR are specified in Outcome Measure 2. MCyR=combined complete cytogenetic and partial cytogenetic response rate. Complete Cytogenetic Response= 0% Ph+ Cells in Metaphase in Bone Marrow, Partial Cytogenetic Response \> 0% to 35% Ph+ Cells in Metaphase in Bone Marrow.
Query!
Timepoint [31]
0
0
Baseline, at time of disease progression. (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).
Query!
Secondary outcome [32]
0
0
Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G)
Query!
Assessment method [32]
0
0
Number of subjects with minimally significant changes from baseline in the health-related quality of life questionnaire FACT-G. FACT-G=27 questions in 4 domains: physical, social/family, emotional, and functional well-being (PWB, SWB, EWB, FWB). Total score=0 to 108; higher score=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, and FWB score change of 3 or more, and SWB score change of 2 or more=minimal clinically important change.
Query!
Timepoint [32]
0
0
Baseline, every 2 weeks for the first 3 cycles, following every 4-week cycle, and once at follow-up.(treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).
Query!
Secondary outcome [33]
0
0
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation
Query!
Assessment method [33]
0
0
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)
Query!
Timepoint [33]
0
0
Continuous from pretreatment through each 4-week cycle and at follow-up. (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).
Query!
Secondary outcome [34]
0
0
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Maximum Observed Plasma Concentration (Cmax)
Query!
Assessment method [34]
0
0
The Cmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.
Query!
Timepoint [34]
0
0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Query!
Secondary outcome [35]
0
0
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 Hours (AUC[0-T])
Query!
Assessment method [35]
0
0
The AUC(0-T) was calculated using the mixed log-linear trapezoidal algorithm in Kinetica™. In the calculation of AUC(0-T), predose concentrations that were less than the lower limit of quantitation (LLQ) were assigned a value of zero.
Query!
Timepoint [35]
0
0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Query!
Secondary outcome [36]
0
0
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Time to Maximum Observed Plasma Concentration (Tmax)
Query!
Assessment method [36]
0
0
The Tmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.
Query!
Timepoint [36]
0
0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Query!
Secondary outcome [37]
0
0
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Plasma Half-life (T-HALF)
Query!
Assessment method [37]
0
0
The T-HALF was calculated as Ln2/Lz,where Lz was the absolute value of the slope of the terminal log-linear phase.
Query!
Timepoint [37]
0
0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Query!
Secondary outcome [38]
0
0
Population PK of Dasatinib
Query!
Assessment method [38]
0
0
Population pharmacokinetic analysis was not done because it is not meaningful for this single study
Query!
Timepoint [38]
0
0
Day 8 immediately prior to the first daily dose and between 30 minutes to 3 hours following this dose.
Query!
Secondary outcome [39]
0
0
Median Duration of Major Hematologic Response (MaHR)
Query!
Assessment method [39]
0
0
MaHR=best confirmed response of CHR or NEL. CHR=white blood cells = institutional upper limit of normal (iULN); absolute neutrophil count (ANC) =1000/mm3; platelets =100,000/mm3; no blasts/promyelocytes in peripheral blood (PB); bone marrow blasts =5%; \<5% myelocytes+metamyelocytes in PB; PB basophils = iULN; no extramedullary involvement. NEL=WBC = iULN; no blasts/promyelocytes in PB; bone marrow blasts =5%; \<5% myelocytes+metamyelocytes in PB; PB basophils = iULN; no extramedullary involvement; at least 1 of the following: ANC =500/mm3 \& \<1000/mm3; platelets =20,000/mm3 \& \<100,000/mm3.
Query!
Timepoint [39]
0
0
Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment
Query!
Secondary outcome [40]
0
0
Median Duration of Overall Hematologic Response (OHR)
Query!
Assessment method [40]
0
0
OHR=best confirmed response of MaHR or MiHR. MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR are specified in Outcome Measure 2. Criteria for MiHR are specified in Outcome Measure 1. Maintaining a response was defined as no 2 consecutive records of non-response (ie, a single record of non-response between 2 assessments of response was not considered a loss of response).
Query!
Timepoint [40]
0
0
Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment
Query!
Secondary outcome [41]
0
0
Time to MaHR and OHR
Query!
Assessment method [41]
0
0
Median time from first dosing to date of OHR and/or MaHR in subjects who achieved OHR and MaHR. MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). OHR=best confirmed response of MaHR or minor hematologic response (MiHR). Criteria for MaHR are specified in Outcome Measure 2. Criteria for MiHR are specified in Outcome Measure 1.
Query!
Timepoint [41]
0
0
Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment
Query!
Secondary outcome [42]
0
0
Number of Participants With Complete, Partial, Minor, Minimal, or No Cytogenetic Response
Query!
Assessment method [42]
0
0
Best confirmed cytogenetic response. Determination of cytogenetic response is based on the prevalence (percentage) of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase in a bone marrow sample (aspirates/biopsies).
Query!
Timepoint [42]
0
0
Baseline (within 4 weeks of therapy start); Every month for Cycles 1-3; Every 12 weeks for Cycles 4+; end of treatment
Query!
Secondary outcome [43]
0
0
Number of Participants With CHR or NEL, MiHR, or no Hematologic Response
Query!
Assessment method [43]
0
0
Best confirmed hematologic response. Confirmed hematologic response=response that is confirmed after at least 4 weeks with no concomitant use of anagrelide or hydroxyurea use during this interval. Criteria for complete hematologic response (CHR) or No Evidence of Leukemia (NEL) are specified in Outcome Measure 2. Criteria for minor hematologic response (MiHR) are specified in Outcome Measure 1.
Query!
Timepoint [43]
0
0
Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycles 1 and 2; After every 2nd cycle for Cycles 3+; at end of treatment
Query!
Secondary outcome [44]
0
0
Number of Participants Achieving Major Molecular Response (MMR)
Query!
Assessment method [44]
0
0
Number of participants who achieved an MMR at any time during the treatment period. MMR was calulated by measuring BCR-ABL transcripts in blood during treatment using quantitative reverse transcription-polymerase chain reaction (RT-PCR). BCR-ABL=the fused gene found in subjects with this type of Chronic Myeloid Leukemia (CML).
Query!
Timepoint [44]
0
0
Baseline, every 12 weeks, and at time of Complete Cytogenetic Response (CCyR) for quantitative Polyermase Chain Reaction (qPCR) analysis
Query!
Secondary outcome [45]
0
0
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
Query!
Assessment method [45]
0
0
MaHR and MCyR in subjects with mutations at baseline, including imatinib-resistant mutations (IRM) and specific BCR-ABL mutations (SBAM). Criteria for MaHR are specified in Outcome Measure 2. MCyR=rate of complete cytogenetic responses + the rate of partial cytogenetic responses, as defined in Outcome Measure 5. BCR-ABL=the fused gene found in subjects with this type of CML. This table contains those mutations observed in at least 3 participants. The categories "1 IRM w/2-4-fold increase in resistance" and "=1 IRM w/=5-fold increase in resistance" refer to increase in resistance to imatinib.
Query!
Timepoint [45]
0
0
baseline, at time of disease progression
Query!
Secondary outcome [46]
0
0
Minimally Significant Changes From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G)
Query!
Assessment method [46]
0
0
Number of subjects with minimally significant changes from baseline in the health-related quality of life questionnaire FACT-G. FACT-G=27 questions in 4 domains: physical, social/family, emotional, \& functional well-being (PWB, SWB, EWB, FWB). Score range: 0-108; higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, \& FWB score change of 3 or more, \& SWB score change of 2 or more=minimal clinical important change.
Query!
Timepoint [46]
0
0
Baseline, Every 2 weeks for the first 3 cycles, following every 4-week cycle, and once at follow-up
Query!
Secondary outcome [47]
0
0
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), AEs Leading to Discontinuation, Drug-Related AEs
Query!
Assessment method [47]
0
0
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)
Query!
Timepoint [47]
0
0
Continuously throughout study, from pre-treatment visit through end of study (due to death, unacceptable toxicity, treatment failure, etc) and follow-up period
Query!
Secondary outcome [48]
0
0
Pharmacokinetics (PK) of Dasatinib - Maximum Observed Plasma Concentration (Cmax)
Query!
Assessment method [48]
0
0
The Cmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.
Query!
Timepoint [48]
0
0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Query!
Secondary outcome [49]
0
0
Pharmacokinetics (PK) of Dasatinib - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 h or 24 h(AUC[0-T])
Query!
Assessment method [49]
0
0
The AUC(0-T) was calculated using the mixed log-linear trapezoidal algorithm in Kinetica™. In the calculation of AUC(0-T), predose concentrations that were \< lower limit of qualtitation were assigned a value of zero.
Query!
Timepoint [49]
0
0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Query!
Secondary outcome [50]
0
0
Pharmacokinetics (PK) of Dasatinib - Time to Maximum Observed Plasma Concentration (Tmax)
Query!
Assessment method [50]
0
0
The Tmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.
Query!
Timepoint [50]
0
0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Query!
Secondary outcome [51]
0
0
Pharmacokinetics (PK) of Dasatinib - Plasma Half-life (T-HALF)
Query!
Assessment method [51]
0
0
The T-HALF was calculated as Ln2/Lz,where Lz was the absolute value of the slope of the terminal log-linear phase.
Query!
Timepoint [51]
0
0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Query!
Secondary outcome [52]
0
0
Pharmacokinetics (PK) of Dasatinib's Metabolite BMS-582691 - Maximum Observed Plasma Concentration (Cmax)
Query!
Assessment method [52]
0
0
The Cmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.
Query!
Timepoint [52]
0
0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Query!
Secondary outcome [53]
0
0
Pharmacokinetics (PK) of Dasatinib's Metabolite BMS-582691 - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 h (AUC[0-T])
Query!
Assessment method [53]
0
0
The AUC(0-T) was calculated using the mixed log-linear trapezoidal algorithm in Kinetica™. In the calculation of AUC(0-T), predose concentrations that were less than the lower limit of quantitation (LLQ) were assigned a value of zero.
Query!
Timepoint [53]
0
0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Query!
Secondary outcome [54]
0
0
Pharmacokinetics (PK) of Dasatinib's Metabolite BMS-582691 - Time to Maximum Observed Plasma Concentration (Tmax)
Query!
Assessment method [54]
0
0
The Tmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.
Query!
Timepoint [54]
0
0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Query!
Secondary outcome [55]
0
0
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Plasma Half-life (T-HALF)
Query!
Assessment method [55]
0
0
The T-HALF was calculated as Ln2/Lz,where Lz was the absolute value of the slope of the terminal log-linear phase.
Query!
Timepoint [55]
0
0
Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.
Query!
Secondary outcome [56]
0
0
Population PK of Dasatinib
Query!
Assessment method [56]
0
0
Population pharmacokinetic analysis was not done because it is not meaningful for this single study
Query!
Timepoint [56]
0
0
Day 8 immediately prior to the first daily dose and between 30 minutes to 3 hours following this dose.
Query!
Secondary outcome [57]
0
0
Percentage of Participants With Major Molecular Response (MMR) Rates at 24, 36, and 42 Months
Query!
Assessment method [57]
0
0
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region \[Bcr\] gene and Abelson proto-oncogene \[Abl\] genes) transcript ratio =0.1% (= 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction \[RT-PCR\] (performed centrally).
Query!
Timepoint [57]
0
0
24, 36 and 42 months
Query!
Secondary outcome [58]
0
0
Percentage of Participants With Objective Response
Query!
Assessment method [58]
0
0
Assessment of complete or partial response (CR, PR) or uncomplete response (CRu) using Response Evaluation Criteria in Solid Tumors. CR: 1) No disease evident. 2) Lymph node, nodal mass regressed to normal size. 3) Previously enlarged organ ? size. 4) Bone marrow clear on repeat aspirate, biopsy. CRu: CR 1 and 3, at least 1 of following: Lymph node regressed \>75%. Bone marrow ? number or aggregate size, no cytologic/architectural atypia. PR: =50% ? index lesion, no size ? in other nodes, liver, spleen. Splenic and hepatic nodule regressed =50%. No new disease.
Query!
Timepoint [58]
0
0
Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)
Query!
Secondary outcome [59]
0
0
Percentage of Participants With Complete Cytogenetic Response (CCyR) Rate at 12, 24, 36, 42 Months
Query!
Assessment method [59]
0
0
Cytogenetic response (CyR)is the percentage of Philadelphia chromosome positive metaphases (among at least 20 metaphase cells in bone marrow (BM)) with Complete Cytogenetic Response (CCyR) being 0 percent.
Query!
Timepoint [59]
0
0
12, 24, 36, 42 months
Query!
Secondary outcome [60]
0
0
Percentage of Participants With Complete Hematological Response (CHR) Rates at 12, 24, 36, and 42 Months
Query!
Assessment method [60]
0
0
Complete Hematologic Response (CHR) is where all of the following criteria must be present for =4 weeks: White Blood Cell (WBC) count \<10 x 109/L, Platelet count \<450 x 109/L, Basophils \<5%, No blasts and promyelocytes in Peripheral Blood (PB), (Myelocytes + metamyelocytes) \< 5% in PB and No evidence of extramedullary involvement.
Query!
Timepoint [60]
0
0
12, 24, 36, and 42 months
Query!
Secondary outcome [61]
0
0
Percentage of Patients With Undetectable Levels of Bcr-Abl (A Fusion Gene of the Breakpoint Cluster Region [Bcr] Gene and Abelson Proto-oncogene [Abl] Genes) Transcripts
Query!
Assessment method [61]
0
0
"Undetectable levels" or Complete molecular response is defined as Bcr-Abl ratio (%) on international scale (IS) \<= 0.0032% (= 4.5 log reduction of BCR-Abl transcripts from a standardized baseline).
Query!
Timepoint [61]
0
0
12 , 24, 36 and 42 months
Query!
Secondary outcome [62]
0
0
Percent of Participants With Major Hematological Response (MaHR) With 2 Years of Follow-up From Date of Last Enrollment - Randomized Population
Query!
Assessment method [62]
0
0
A MaHR was defined as a participant having either CHR or NEL. CHR was defined as: WBC = ULN; ANC = 1,000/mm\^3; - platelets = 100,000/mm\^3; - no blasts or promyelocytes in PB; BM blasts = 5%; \< 5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (both lower limits had to be satisfied): platelets = 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percent: number of participants with MaHR /number of participants randomized.
Query!
Timepoint [62]
0
0
Randomization up to 2 years
Query!
Secondary outcome [63]
0
0
Percent of Participants With Major Hematologic Response (MaHR) by Disease Group - Randomized Population
Query!
Assessment method [63]
0
0
MaHR was defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) = upper limit of normal (ULN); absolute neutrophil count (ANC) = 1,000/mm\^3; platelets = 100,000/mm\^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts = 5%; \<5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one parameter of the following (note that both lower limits had to be satisfied): platelets = 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule.. Percentage: participants with MaHR/randomized participants.
Query!
Timepoint [63]
0
0
Randomization up to 2 years
Query!
Secondary outcome [64]
0
0
Median Time to Major Hematologic Response (MaHR) - Randomized Population
Query!
Assessment method [64]
0
0
A participants' time to MaHR was defined as the time from the first dosing date until criteria are first met for CHR or NEL, whichever occurred first. Non-responders were censored at the maximum of the date of last hematologic or cytogenetic assessment. Median time was measured in months.
Query!
Timepoint [64]
0
0
Day 1 up to 6 months (time of primary endpoint), 2 years
Query!
Secondary outcome [65]
0
0
Time to First Major Molecular Response
Query!
Assessment method [65]
0
0
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region \[Bcr\] gene and Abelson proto-oncogene \[Abl\] genes) transcript ratio =0.1% (= 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction \[RT-PCR\] (performed centrally).
Time to MMR (months) = (date of first MMR or censoring - date of randomization + 1) / 30.4375. Time to first MMR was evaluated using the Kaplan-Meier method
Query!
Timepoint [65]
0
0
42 months overall
Query!
Secondary outcome [66]
0
0
Median Duration of a Major Hematologic Response (MaHR) in Those Participants Who Achieved a MaHR During the Study
Query!
Assessment method [66]
0
0
MaHR was defined by either CHR or no evidence of leukemia NEL. CHR was defined as: WBC = ULN; ANC = 1,000/mm\^3; - platelets = 100,000/mm\^3; - no blasts or promyelocytes in PB; BM blasts = 5%; \< 5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets = 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. Median duration was measured in months.
Query!
Timepoint [66]
0
0
Day 1 up to 5 years
Query!
Secondary outcome [67]
0
0
Time to First Complete Cytogenetic Response
Query!
Assessment method [67]
0
0
Cytogenetic response (CyR) is the percentage of Philadelphia positive metaphases (among at least 20 metaphase cells in Bone Marrow) with Complete Cytogenetic Response (CCyR) being 0 percent. Time to CCyR (months) = (date of first CCyR or censoring - date of randomization + 1) / 30.4375. Time to first CCyR was evaluated using the Kaplan-Meier method.
Query!
Timepoint [67]
0
0
60 months overall
Query!
Secondary outcome [68]
0
0
Time to First Complete Hematological Response (CHR)]
Query!
Assessment method [68]
0
0
Complete Hematological Response (CHR) is defined is where all of the following criteria must be present for =4 weeks: White Blood Cell (WBC) count \<10 x 109/L, Platelet count \<450 x 109/L, Basophils \<5%, No blasts and promyelocytes in Peripheral Blood (PB), (Myelocytes + metamyelocytes) \< 5% in PB and No evidence of extramedullary involvement. Time to CHR (months) = (date of first CHR or censoring - date of randomization + 1) / 30.4375. Time to first CHR was evaluated using the Kaplan-Meier method.
Query!
Timepoint [68]
0
0
60 months overall
Query!
Secondary outcome [69]
0
0
Percent of Participants With Overall Hematologic Response - Randomized Population
Query!
Assessment method [69]
0
0
Overall Hematologic Response (OHR) was defined as CHR, NEL or minor hematologic response (MiHR). CHR was defined as: WBC = ULN; ANC = 1,000/mm\^3; - platelets = 100,000/mm\^3; - no blasts or promyelocytes in PB; BM blasts = 5%; \< 5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets = 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. MiHR defined as: \< 15% blasts in BM and in PB; \< 30% blasts + promyelocytes in BM and PB; \< 20% basophils in PB; No extra-medullary disease other than spleen and liver. Percentage: participants with OHR/ randomized participants.
Query!
Timepoint [69]
0
0
Randomization up to 6 Months, 2 Years
Query!
Secondary outcome [70]
0
0
Estimated Rate of Event Free Survival (EFS) in Two Treatment Arms
Query!
Assessment method [70]
0
0
EFS on treatment was defined as time between randomization and either (1) death due to any cause during study treatment, (2) progression to accelerated phase (AP) or blast crisis (BC) on treatment, (3) loss of complete hematological response (CHR), or (4) loss of major cytogenic response (MCyR) while on treatment. Estimated rate of EFS was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Query!
Timepoint [70]
0
0
60 months over all
Query!
Secondary outcome [71]
0
0
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population
Query!
Assessment method [71]
0
0
Type of hematologic response: CHR defined as: WBC = ULN; ANC = 1,000/mm\^3; - platelets = 100,000/mm\^3; - no blasts or promyelocytes in PB; BM blasts = 5%; \< 5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets = 20,000/mm\^3 and \<100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. Minor Hematologic Response (MiHR): \<15% blasts in BM and in PB; \< 30% blasts + promyelocytes in BM and PB; \< 20% basophils in PB; No extra-medullary disease other than spleen and liver. Major hematologic response (MaHR ) was CHR or NEL. Overall hematologic response was CHR or NEL or MiHR.
Query!
Timepoint [71]
0
0
Randomization up to 6 months, 2 years
Query!
Secondary outcome [72]
0
0
Estimated Rate of Progression Free Survival (PFS) in Two Treatment Arms
Query!
Assessment method [72]
0
0
PFS on study which was defined as time between randomization and either (1) death due to any cause on treatment of during follow-up after discontinuation of treatment or (2) progression to accelerated phase (AP) or blast crisis (BC) on treatment during follow-up after discontinuation of study treatment. Estimated rate of PFS was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Query!
Timepoint [72]
0
0
60 months over all and follow up period
Query!
Secondary outcome [73]
0
0
Percent of Participants With Major Cytogenetic Response (MCyR) - Randomized Population
Query!
Assessment method [73]
0
0
Cytogenetic assessments were performed only for the first 2 years of study. CyR was based on the number of Ph+ metaphases among cells in metaphase on a BM sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): 1% to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: 36% to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: 66% to 95% Ph+ cells in metaphase in BM; No cytogenetic response: 96% to 100% Ph+ cells in metaphase in BM; Major cytogenetic response (MCyR) was defined as CCyR or PCyR. Percentage: number of participants with MCyR and denominator is number of randomized participants.
Query!
Timepoint [73]
0
0
Randomization up to 6 Months, 2 Years
Query!
Secondary outcome [74]
0
0
Estimated Rate of Progression to Accelerated Phase (AC)/Blast Crisis (BC) in Two Treatment Arms
Query!
Assessment method [74]
0
0
(Accelerated Phase/Blast Crisis) AP/BC was defined as time between randomization and either (1) (Chronic Myeloid Leukemia) CML-related death (if death was primary reason for discontinuation) or (2) progression to AP or BC (during treatment). Estimated rate of AC/BC was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Query!
Timepoint [74]
0
0
60 months over all and follow up period
Query!
Secondary outcome [75]
0
0
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population
Query!
Assessment method [75]
0
0
Cytogenetic assessments were performed only for the first 2 years of study. CyR was based on the number of Ph+ metaphases among cells in metaphase on a BM sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): 1% to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: 36% to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: 66% to 95% Ph+ cells in metaphase in BM; No cytogenetic response: 96% to 100% Ph+ cells in metaphase in BM.
Query!
Timepoint [75]
0
0
Randomization up to 6 Months, 2 Years
Query!
Secondary outcome [76]
0
0
Median Progression Free Survival (PFS) - Randomized Population
Query!
Assessment method [76]
0
0
PFS was defined as: Time from randomization until any of the following: Progression of disease (per investigator), or death. For those with blast phase CML or Ph+ ALL, disease progression was: loss of OHR; no decrease from on-study baseline percent blasts in PB or BM on all assessments over a 4-week period after starting maximum dose; absolute increase of at least 50% in PB blast count over a 2-week period after starting maximum dose. For those with accelerated phase CML: the list above also included: Development of blast phase CML at any time after initiation of therapy and development of extra-medullary sites other than spleen or liver. Participants who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. Median duration was measured in months.
Query!
Timepoint [76]
0
0
Randomization up to 5 Years
Query!
Secondary outcome [77]
0
0
Estimated Rate of Overall Survival (OS) in Two Treatment Arms
Query!
Assessment method [77]
0
0
OS was defined as time between randomization and death due to any cause during study treatment or during follow-up after discontinuation of treatment. Estimated rate of OS was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Query!
Timepoint [77]
0
0
60 months over all and follow up period
Query!
Secondary outcome [78]
0
0
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
Query!
Assessment method [78]
0
0
Duration of MMR (months) = (date of first confirmed loss or censoring - date of MMR + 1 ) / 30.4375. Estimated rate of duration of first MMR was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Query!
Timepoint [78]
0
0
From First major molecular response to first confirmed loss or censoring
Query!
Secondary outcome [79]
0
0
Median Overall Survival (OS) - Randomized Population
Query!
Assessment method [79]
0
0
OS was defined as time from randomization until date of death. Participants who had not died or who were lost to follow-up were censored on the last date on which the participant was known to be alive. Median duration was measured in months.
Query!
Timepoint [79]
0
0
Randomization up to 5 Years
Query!
Secondary outcome [80]
0
0
Kaplan-Meier Estimates of Duration of First Complete Cytogenetic Response (CCyR)
Query!
Assessment method [80]
0
0
Duration of CCyR was defined as the time between date of CCyR and the earliest of either (1) loss of CCyR OR (2) (Chronic Myeloid Leukemia) CML-related death or progression to (Accelerated Phase/Blast Crisis) AP/BC during study treatment. Estimated rate of duration of first CCyR was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Query!
Timepoint [80]
0
0
From first complete cytogenetic response to first confirmed loss or censoring
Query!
Secondary outcome [81]
0
0
Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population
Query!
Assessment method [81]
0
0
PFS was defined as time from randomization until any of the following: Progression of disease (per investigator), or death. For those with blast phase CML or Ph+ ALL, disease progression was: loss of OHR; no decrease from on-study baseline percent blasts in PB or BM on all assessments over a 4-week period after starting maximum dose; absolute increase of at least 50% in PB blast count over a 2-week period after starting maximum dose. For those with accelerated phase CML: the list above also included: Development of blast phase CML at any time after initiation of therapy and development of extra-medullary sites other than spleen or liver. Participants who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. OS was defined as time from randomization until date of death. Participants who had not died or were lost to follow-up were censored on the last date they were known to be alive. Median duration was measured in months.
Query!
Timepoint [81]
0
0
24 months, 36 months, 48 months, 60 months
Query!
Secondary outcome [82]
0
0
Mean Actual Dose Intensity Per Day
Query!
Assessment method [82]
0
0
The mean actual dose intensity per day from start of treatment up to last dose or discontinuation was evaluated up to Month 36. Actual dose intensity (mg/day) = total dose/time on treatment (periods of zero dose are included)
Query!
Timepoint [82]
0
0
start of treatment to Month 36
Query!
Secondary outcome [83]
0
0
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation and Drug-related Fluid Retention AEs, up to Year 7 in Treated Participants
Query!
Assessment method [83]
0
0
With protocol Amendment 6, the duration of the study was extended for 2 additional years (7 years total) for participants who continued to have clinical benefit and no feasible alternate access to dasatinib. However, after Year 5 the requirement to follow participants for survival and to collect other efficacy data was removed from the protocol for the remainder of the study. Only AEs and SAEs were collected up to Year 7. On-study AEs and SAEs were graded by severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. The investigator AE terms were coded and grouped by preferred term and system organ class using the Medical Dictionary for Regulatory Activities (MedDRA), version 16.0.
Query!
Timepoint [83]
0
0
Day 1 to Year 7
Query!
Secondary outcome [84]
0
0
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants
Query!
Assessment method [84]
0
0
Laboratory abnormalities were graded according to the National Cancer Institute Common Terminology Criteria (NCI CTC) version 3.0. CTC Grade 3 and 4 criteria are defined as follows: White blood cells (WBC): Grade (Gr) 3:\<2.0 to 1.0\*10\^9/L, Gr 4:\<1.0\*10\^9/L. Absolute neutrophil count (ANC): Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L. Platelet count Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L. Hemoglobin Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL. Baseline was laboratory value obtained within 2 weeks prior to randomization.
Query!
Timepoint [84]
0
0
Baseline to Year 2
Query!
Secondary outcome [85]
0
0
Imatinib Pharmacokinetic Trough Plasma Concentration (Cmin) at Month 12
Query!
Assessment method [85]
0
0
Imatinib PK trough plasma concentration (Cmin) was defined as any pre-dose Imatinib plasma concentration
Query!
Timepoint [85]
0
0
Month 12
Query!
Secondary outcome [86]
0
0
Number of Participants With Grade 4 Myelosuppression Determined From Hematology Evaluations
Query!
Assessment method [86]
0
0
Laboratory abnormalities were graded according to the National Cancer Institute Common Terminology Criteria (NCI CTC) Version 3.0. Grade 4 hematology evaluations used to determine myelosuppression included: WBC: \<1.0\*10\^9/L. ANC: \<0.5\*10\^9/L. Platelet count \<25.0 to 10\^9/L.
Query!
Timepoint [86]
0
0
Day 1 up to Year 7
Query!
Secondary outcome [87]
0
0
Estimated Rates of Progression Free Survival (PFS) on Treatment by Major Molecular Response (MMR)
Query!
Assessment method [87]
0
0
A Landmark Kaplan-Meier analysis was performed for PFS at 42 months by MMR status at 6, 12, and 18 months to investigate their prognostic value.
Query!
Timepoint [87]
0
0
42 months
Query!
Secondary outcome [88]
0
0
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants
Query!
Assessment method [88]
0
0
Laboratory abnormalities were graded according to the NCI CTC version 3.0. Grade 3 and 4 criteria were defined as follows: Upper limit of normal (ULN). Alanine transaminase (ALT) Grade (Gr) 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. Aspartate aminotransferase (AST) Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. Total bilirubin Gr 3: \>3.0 to 10..0\*ULN; Gr 4: \>10.0.0\*ULN. Serum creatinine (H) Gr 3: \>3.0 to 6.0\*ULN; Gr 4: \>6.0\*ULN. Calcium (L) Gr3: 6.0-7.0; Gr 4: \<6.0 mg/dL; Phosphorus (L): Gr 3: \<2.0 - 1.0 mg/dL , Gr 4: \<1.0 mg/dL. Non-hematologic laboratory results were not collected beyond Year 2. Baseline values were obtained within 2 weeks prior to randomization.
Query!
Timepoint [88]
0
0
Baseline to Year 2
Query!
Secondary outcome [89]
0
0
Time to First Complete Molecular Response (CMR)]
Query!
Assessment method [89]
0
0
Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio =0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene.
Query!
Timepoint [89]
0
0
48 months overall
Query!
Secondary outcome [90]
0
0
Number of Participants With Changes From Baseline in QT Interval Corrected With Fridericia Formula (QTcF) up to Year 2 in Treated Participants
Query!
Assessment method [90]
0
0
A12-lead electrocardiogram (ECG) was obtained at baseline (baseline=within 2 weeks prior to randomization) and once between Days 8 and 29. Additional ECGs were done at the Investigator's discretion. ECGs were read centrally. The QT interval corrected with Fridericia formula is presented with categories of changes from baseline (BL) in milliseconds (msec).
Query!
Timepoint [90]
0
0
Baseline to Year 2
Query!
Secondary outcome [91]
0
0
Number of Participants With the Effect of Imatinib on the Diabetic Participants With Known Concomitant Type II Diabetes
Query!
Assessment method [91]
0
0
Query!
Timepoint [91]
0
0
12 months
Query!
Secondary outcome [92]
0
0
Number of Participants With Maximal QTcF Intervals up to Year 2 in Treated Participants
Query!
Assessment method [92]
0
0
A12-lead ECG was obtained at baseline (baseline=within 2 weeks prior to randomization) and once between Day 8 and 29. Additional ECGs were done at the Investigator's discretion. ECGs were read centrally. QT Interval corrected with Fridericia formula was measured in msec.
Query!
Timepoint [92]
0
0
Baseline up to Year 2
Query!
Secondary outcome [93]
0
0
Number of Imatinib-intolerant Participants With MCyR
Query!
Assessment method [93]
0
0
Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases.
Query!
Timepoint [93]
0
0
Baseline to 2 years
Query!
Secondary outcome [94]
0
0
Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months
Query!
Assessment method [94]
0
0
Based on the Kaplan-Meier estimate of the duration of response. Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases and Partial Cytogenetic Response (PCyR) - 1% to 35% Ph+ metaphases.
Query!
Timepoint [94]
0
0
12 and 24 Months
Query!
Secondary outcome [95]
0
0
Median Time From First Dosing Date to Date of MCyR
Query!
Assessment method [95]
0
0
MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases.
Query!
Timepoint [95]
0
0
Baseline (within 4 weeks of Day 1) and every 12 weeks
Query!
Secondary outcome [96]
0
0
Durability of hematologic response and time to hematologic response (major and overall)
Query!
Assessment method [96]
0
0
Query!
Timepoint [96]
0
0
throughout the study
Query!
Secondary outcome [97]
0
0
Number of Participants With Complete Hematologic Response (CHR)
Query!
Assessment method [97]
0
0
CHR=all of the following criteria: white blood cell count = institutional upper limit of normal; platelets \<450,000/mm\^3; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils =20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.
Query!
Timepoint [97]
0
0
Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study
Query!
Secondary outcome [98]
0
0
Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months
Query!
Assessment method [98]
0
0
Based on the Kaplan-Meier estimate of the duration of response. CHR=all of the following criteria: white blood cell count = institutional upper limit of normal; platelets \< 450,000/mm\^3; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils =20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.
Query!
Timepoint [98]
0
0
12 and 24 months
Query!
Secondary outcome [99]
0
0
Assess cytogenetic and molecular responses
Query!
Assessment method [99]
0
0
Query!
Timepoint [99]
0
0
throughout the study
Query!
Secondary outcome [100]
0
0
Measure minor hematologic response rate in the imatinib resistant group
Query!
Assessment method [100]
0
0
Query!
Timepoint [100]
0
0
throughout the study
Query!
Secondary outcome [101]
0
0
Explore the role of BCR-ABL mRNA expression and point mutations in the BCR-ABL gene
Query!
Assessment method [101]
0
0
Query!
Timepoint [101]
0
0
throughout the study
Query!
Secondary outcome [102]
0
0
Median Time From First Dosing Until CHR
Query!
Assessment method [102]
0
0
CHR=all of the following criteria: white blood cell count = institutional upper limit of normal; platelets \<450,000/mm\^3; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils =20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.
Query!
Timepoint [102]
0
0
Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study
Query!
Secondary outcome [103]
0
0
Measure the heath-related QOL using FACT-G
Query!
Assessment method [103]
0
0
Query!
Timepoint [103]
0
0
throughout the study
Query!
Secondary outcome [104]
0
0
Number of Participants With Major Molecular Response (MMR)
Query!
Assessment method [104]
0
0
MMR is defined as =3 log reduction in BCR-ABL levels from the standardized baseline value of BCR-ABL:Control Gene ratio. The international ratio is obtained by multiplying BCR-ABL:Control gene ratio by the lab-specific conversion factor.
Query!
Timepoint [104]
0
0
Baseline to 2 years
Query!
Secondary outcome [105]
0
0
To assess safety and tolerability of dasatinib
Query!
Assessment method [105]
0
0
Query!
Timepoint [105]
0
0
throughout the study
Query!
Secondary outcome [106]
0
0
Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores
Query!
Assessment method [106]
0
0
Health-related quality of life as measured by FACT-G, which comprises 27 questions in 4 domains: PWB, SWB, EWB, FWB. Total FACT-G score=summation of the 4 subscale scores and ranges from 0 to 108. Higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, \& FWB score change of 3 or more, and SWB score change of 2 or more=minimal clinical important change. Baseline FACT-G measurements can be found in Baseline Characteristics.
Query!
Timepoint [106]
0
0
Baseline, Day 29, every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment, after end of treatment. Treatment continued until disease progression or development of toxicity or until other protocol-defined criteria.
Query!
Secondary outcome [107]
0
0
Population PK
Query!
Assessment method [107]
0
0
Query!
Timepoint [107]
0
0
first month
Query!
Secondary outcome [108]
0
0
Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE
Query!
Assessment method [108]
0
0
AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)
Query!
Timepoint [108]
0
0
Continuously, from baseline through 2 years
Query!
Secondary outcome [109]
0
0
Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE
Query!
Assessment method [109]
0
0
AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)
Query!
Timepoint [109]
0
0
Continuously, from baseline through 2 years
Query!
Secondary outcome [110]
0
0
Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib
Query!
Assessment method [110]
0
0
Blood samples were collected for PK to be included in separate population PK analyses.
Query!
Timepoint [110]
0
0
Day 8 of study; pretreatment through sample between 30 minutes and 3 hours following treatment, a sample between 5 hours and 8 hours following treatment and a sample at 12 hours, prior to the next dose.
Query!
Eligibility
Key inclusion criteria
* Histologically confirmed renal cell carcinoma of clear cell histology with metastases
* Evidence of measurable disease by radiographic technique
* Eastern Cooperative Oncology Group [ECOG] performance status of 0 or 1
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* Prior systemic (including adjuvant or neoadjuvant) therapy of any kind for RCC
* History of or known brain metastases
* Serious acute or chronic illness or recent history of significant cardiac abnormality
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/08/2004
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
1/09/2008
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
750
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Query!
Recruitment hospital [1]
0
0
Pfizer Investigational Site - Lismore
Query!
Recruitment hospital [2]
0
0
Pfizer Investigational Site - St. Leonards
Query!
Recruitment hospital [3]
0
0
Pfizer Investigational Site - South Brisbane
Query!
Recruitment hospital [4]
0
0
Pfizer Investigational Site - Woodville South
Query!
Recruitment hospital [5]
0
0
Pfizer Investigational Site - East Melbourne
Query!
Recruitment hospital [6]
0
0
Pfizer Investigational Site - Perth
Query!
Recruitment hospital [7]
0
0
Pfizer Investigational Site - Victoria
Query!
Recruitment hospital [8]
0
0
Local Institution - St. Leonards
Query!
Recruitment hospital [9]
0
0
Local Institution - South Brisbane
Query!
Recruitment hospital [10]
0
0
Local Institution - East Melbourne
Query!
Recruitment hospital [11]
0
0
Local Institution - Parkville
Query!
Recruitment hospital [12]
0
0
Local Institution - Wien
Query!
Recruitment hospital [13]
0
0
Local Institution - Adelaide
Query!
Recruitment hospital [14]
0
0
Local Institution - St Leonards
Query!
Recruitment hospital [15]
0
0
Local Institution - Perth
Query!
Recruitment hospital [16]
0
0
Novartis Investigative Site - St. Leonards
Query!
Recruitment hospital [17]
0
0
Novartis Investigative Site - Waratah
Query!
Recruitment hospital [18]
0
0
Novartis Investigative Site - Westmead
Query!
Recruitment hospital [19]
0
0
Novartis Investigative Site - Herston
Query!
Recruitment hospital [20]
0
0
Novartis Investigative Site - Woolloongabba
Query!
Recruitment hospital [21]
0
0
Novartis Investigative Site - Adelaide
Query!
Recruitment hospital [22]
0
0
Novartis Investigative Site - East Melbourne
Query!
Recruitment hospital [23]
0
0
Novartis Investigative Site - Fitzroy
Query!
Recruitment hospital [24]
0
0
Novartis Investigative Site - Frankston
Query!
Recruitment hospital [25]
0
0
Novartis Investigative Site - Parkville
Query!
Recruitment hospital [26]
0
0
Novartis Investigative Site - Prahran
Query!
Recruitment hospital [27]
0
0
Novartis Investigative Site - South Brisbane
Query!
Recruitment hospital [28]
0
0
Local Institution - East Mebourne
Query!
Recruitment postcode(s) [1]
0
0
2480 - Lismore
Query!
Recruitment postcode(s) [2]
0
0
2065 - St. Leonards
Query!
Recruitment postcode(s) [3]
0
0
4101 - South Brisbane
Query!
Recruitment postcode(s) [4]
0
0
5011 - Woodville South
Query!
Recruitment postcode(s) [5]
0
0
3002 - East Melbourne
Query!
Recruitment postcode(s) [6]
0
0
6000 - Perth
Query!
Recruitment postcode(s) [7]
0
0
36184 - Victoria
Query!
Recruitment postcode(s) [8]
0
0
- St. Leonards
Query!
Recruitment postcode(s) [9]
0
0
- South Brisbane
Query!
Recruitment postcode(s) [10]
0
0
- East Melbourne
Query!
Recruitment postcode(s) [11]
0
0
- Parkville
Query!
Recruitment postcode(s) [12]
0
0
- Wien
Query!
Recruitment postcode(s) [13]
0
0
- Adelaide
Query!
Recruitment postcode(s) [14]
0
0
3000 - East Melbourne
Query!
Recruitment postcode(s) [15]
0
0
2065 - St Leonards
Query!
Recruitment postcode(s) [16]
0
0
SA 5000 - Adelaide
Query!
Recruitment postcode(s) [17]
0
0
3050 - Parkville
Query!
Recruitment postcode(s) [18]
0
0
WA 6000 - Perth
Query!
Recruitment postcode(s) [19]
0
0
- Waratah
Query!
Recruitment postcode(s) [20]
0
0
- Westmead
Query!
Recruitment postcode(s) [21]
0
0
- Herston
Query!
Recruitment postcode(s) [22]
0
0
- Woolloongabba
Query!
Recruitment postcode(s) [23]
0
0
- Fitzroy
Query!
Recruitment postcode(s) [24]
0
0
- Frankston
Query!
Recruitment postcode(s) [25]
0
0
- Prahran
Query!
Recruitment postcode(s) [26]
0
0
- East Mebourne
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Arkansas
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
California
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Colorado
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Connecticut
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Florida
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Illinois
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Kansas
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Kentucky
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
Louisiana
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Maryland
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
Massachusetts
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
Michigan
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
Minnesota
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Mississippi
Query!
Country [15]
0
0
United States of America
Query!
State/province [15]
0
0
Missouri
Query!
Country [16]
0
0
United States of America
Query!
State/province [16]
0
0
Nebraska
Query!
Country [17]
0
0
United States of America
Query!
State/province [17]
0
0
New Hampshire
Query!
Country [18]
0
0
United States of America
Query!
State/province [18]
0
0
New York
Query!
Country [19]
0
0
United States of America
Query!
State/province [19]
0
0
Ohio
Query!
Country [20]
0
0
United States of America
Query!
State/province [20]
0
0
Oklahoma
Query!
Country [21]
0
0
United States of America
Query!
State/province [21]
0
0
Oregon
Query!
Country [22]
0
0
United States of America
Query!
State/province [22]
0
0
Pennsylvania
Query!
Country [23]
0
0
United States of America
Query!
State/province [23]
0
0
Tennessee
Query!
Country [24]
0
0
United States of America
Query!
State/province [24]
0
0
Texas
Query!
Country [25]
0
0
United States of America
Query!
State/province [25]
0
0
Utah
Query!
Country [26]
0
0
United States of America
Query!
State/province [26]
0
0
Washington
Query!
Country [27]
0
0
United States of America
Query!
State/province [27]
0
0
Wisconsin
Query!
Country [28]
0
0
Brazil
Query!
State/province [28]
0
0
RJ
Query!
Country [29]
0
0
Brazil
Query!
State/province [29]
0
0
RS
Query!
Country [30]
0
0
Canada
Query!
State/province [30]
0
0
Alberta
Query!
Country [31]
0
0
Canada
Query!
State/province [31]
0
0
British Columbia
Query!
Country [32]
0
0
Canada
Query!
State/province [32]
0
0
Ontario
Query!
Country [33]
0
0
Canada
Query!
State/province [33]
0
0
Quebec
Query!
Country [34]
0
0
France
Query!
State/province [34]
0
0
Cedex 15
Query!
Country [35]
0
0
France
Query!
State/province [35]
0
0
Lyon
Query!
Country [36]
0
0
France
Query!
State/province [36]
0
0
Paris Cedex 13
Query!
Country [37]
0
0
France
Query!
State/province [37]
0
0
Rennes
Query!
Country [38]
0
0
France
Query!
State/province [38]
0
0
Saint Herblain
Query!
Country [39]
0
0
France
Query!
State/province [39]
0
0
Vandoeuvre Les Nancy
Query!
Country [40]
0
0
Germany
Query!
State/province [40]
0
0
Aachen
Query!
Country [41]
0
0
Germany
Query!
State/province [41]
0
0
Essen
Query!
Country [42]
0
0
Germany
Query!
State/province [42]
0
0
Hannover
Query!
Country [43]
0
0
Germany
Query!
State/province [43]
0
0
Ulm
Query!
Country [44]
0
0
Italy
Query!
State/province [44]
0
0
Modena
Query!
Country [45]
0
0
Italy
Query!
State/province [45]
0
0
Napoli
Query!
Country [46]
0
0
Italy
Query!
State/province [46]
0
0
Pavia
Query!
Country [47]
0
0
Italy
Query!
State/province [47]
0
0
Roma
Query!
Country [48]
0
0
Poland
Query!
State/province [48]
0
0
Warszawa
Query!
Country [49]
0
0
Poland
Query!
State/province [49]
0
0
Gdansk
Query!
Country [50]
0
0
Poland
Query!
State/province [50]
0
0
Krakow
Query!
Country [51]
0
0
Poland
Query!
State/province [51]
0
0
Lodz
Query!
Country [52]
0
0
Poland
Query!
State/province [52]
0
0
Lublin
Query!
Country [53]
0
0
Poland
Query!
State/province [53]
0
0
Poznan
Query!
Country [54]
0
0
Poland
Query!
State/province [54]
0
0
Wroclaw
Query!
Country [55]
0
0
Russian Federation
Query!
State/province [55]
0
0
Kaluga Region
Query!
Country [56]
0
0
Russian Federation
Query!
State/province [56]
0
0
Chelyabinsk
Query!
Country [57]
0
0
Russian Federation
Query!
State/province [57]
0
0
Moscow
Query!
Country [58]
0
0
Russian Federation
Query!
State/province [58]
0
0
Saint-Petersburg
Query!
Country [59]
0
0
Russian Federation
Query!
State/province [59]
0
0
St. Petersburg
Query!
Country [60]
0
0
Russian Federation
Query!
State/province [60]
0
0
Tomsk
Query!
Country [61]
0
0
Spain
Query!
State/province [61]
0
0
Barcelona
Query!
Country [62]
0
0
Spain
Query!
State/province [62]
0
0
Navarra
Query!
Country [63]
0
0
Spain
Query!
State/province [63]
0
0
Madrid
Query!
Country [64]
0
0
Spain
Query!
State/province [64]
0
0
Sevilla
Query!
Country [65]
0
0
United Kingdom
Query!
State/province [65]
0
0
Cardiff
Query!
Country [66]
0
0
United Kingdom
Query!
State/province [66]
0
0
Lancashire
Query!
Country [67]
0
0
United Kingdom
Query!
State/province [67]
0
0
Middlesex
Query!
Country [68]
0
0
United Kingdom
Query!
State/province [68]
0
0
London
Query!
Country [69]
0
0
United Kingdom
Query!
State/province [69]
0
0
Sutton Surrey
Query!
Country [70]
0
0
United States of America
Query!
State/province [70]
0
0
Alabama
Query!
Country [71]
0
0
United States of America
Query!
State/province [71]
0
0
Georgia
Query!
Country [72]
0
0
United States of America
Query!
State/province [72]
0
0
New Jersey
Query!
Country [73]
0
0
Argentina
Query!
State/province [73]
0
0
Buenos Aires
Query!
Country [74]
0
0
Argentina
Query!
State/province [74]
0
0
Cordoba
Query!
Country [75]
0
0
Belgium
Query!
State/province [75]
0
0
B-Leuven
Query!
Country [76]
0
0
Belgium
Query!
State/province [76]
0
0
Edegem
Query!
Country [77]
0
0
Brazil
Query!
State/province [77]
0
0
Campinas
Query!
Country [78]
0
0
Brazil
Query!
State/province [78]
0
0
Rio De Janeiro
Query!
Country [79]
0
0
Brazil
Query!
State/province [79]
0
0
Sao Paulo
Query!
Country [80]
0
0
Denmark
Query!
State/province [80]
0
0
Aarhus
Query!
Country [81]
0
0
Finland
Query!
State/province [81]
0
0
Helsinki
Query!
Country [82]
0
0
France
Query!
State/province [82]
0
0
LIlle
Query!
Country [83]
0
0
France
Query!
State/province [83]
0
0
Lyon Cedex 03
Query!
Country [84]
0
0
France
Query!
State/province [84]
0
0
Nantes
Query!
Country [85]
0
0
France
Query!
State/province [85]
0
0
Paris
Query!
Country [86]
0
0
France
Query!
State/province [86]
0
0
Pessac
Query!
Country [87]
0
0
France
Query!
State/province [87]
0
0
Poitiers Cedex
Query!
Country [88]
0
0
France
Query!
State/province [88]
0
0
Strasbourg Cedex
Query!
Country [89]
0
0
Germany
Query!
State/province [89]
0
0
Hamburg
Query!
Country [90]
0
0
Germany
Query!
State/province [90]
0
0
Mainz
Query!
Country [91]
0
0
Germany
Query!
State/province [91]
0
0
Mannheim
Query!
Country [92]
0
0
Israel
Query!
State/province [92]
0
0
Ramat-Gan
Query!
Country [93]
0
0
Italy
Query!
State/province [93]
0
0
Bologna
Query!
Country [94]
0
0
Italy
Query!
State/province [94]
0
0
Orbassano
Query!
Country [95]
0
0
Korea, Republic of
Query!
State/province [95]
0
0
Jeollanam-Do
Query!
Country [96]
0
0
Korea, Republic of
Query!
State/province [96]
0
0
Kyunggi-Do
Query!
Country [97]
0
0
Korea, Republic of
Query!
State/province [97]
0
0
Seoul
Query!
Country [98]
0
0
Netherlands
Query!
State/province [98]
0
0
Nijmegen
Query!
Country [99]
0
0
Netherlands
Query!
State/province [99]
0
0
Rotterdam
Query!
Country [100]
0
0
Norway
Query!
State/province [100]
0
0
Trondheim
Query!
Country [101]
0
0
Peru
Query!
State/province [101]
0
0
Lima
Query!
Country [102]
0
0
Philippines
Query!
State/province [102]
0
0
Quezon City
Query!
Country [103]
0
0
Singapore
Query!
State/province [103]
0
0
Singapore
Query!
Country [104]
0
0
Sweden
Query!
State/province [104]
0
0
Gothenburg
Query!
Country [105]
0
0
Sweden
Query!
State/province [105]
0
0
Lund
Query!
Country [106]
0
0
Sweden
Query!
State/province [106]
0
0
Umea
Query!
Country [107]
0
0
Sweden
Query!
State/province [107]
0
0
Uppsala
Query!
Country [108]
0
0
Switzerland
Query!
State/province [108]
0
0
Basel
Query!
Country [109]
0
0
Taiwan
Query!
State/province [109]
0
0
Taipei
Query!
Country [110]
0
0
Taiwan
Query!
State/province [110]
0
0
Taoyuan
Query!
Country [111]
0
0
Thailand
Query!
State/province [111]
0
0
Bangkok
Query!
Country [112]
0
0
United Kingdom
Query!
State/province [112]
0
0
Central
Query!
Country [113]
0
0
United Kingdom
Query!
State/province [113]
0
0
Greater London
Query!
Country [114]
0
0
Austria
Query!
State/province [114]
0
0
Wien
Query!
Country [115]
0
0
France
Query!
State/province [115]
0
0
Lille
Query!
Country [116]
0
0
France
Query!
State/province [116]
0
0
Paris Cedex 10
Query!
Country [117]
0
0
United States of America
Query!
State/province [117]
0
0
District of Columbia
Query!
Country [118]
0
0
United States of America
Query!
State/province [118]
0
0
Hawaii
Query!
Country [119]
0
0
Belgium
Query!
State/province [119]
0
0
Brugge
Query!
Country [120]
0
0
Belgium
Query!
State/province [120]
0
0
Gent
Query!
Country [121]
0
0
Belgium
Query!
State/province [121]
0
0
Leuven
Query!
Country [122]
0
0
United States of America
Query!
State/province [122]
0
0
Indiana
Query!
Country [123]
0
0
Brazil
Query!
State/province [123]
0
0
Porto Alegre - RS
Query!
Country [124]
0
0
United States of America
Query!
State/province [124]
0
0
Iowa
Query!
Country [125]
0
0
Chile
Query!
State/province [125]
0
0
Santiago
Query!
Country [126]
0
0
United States of America
Query!
State/province [126]
0
0
North Carolina
Query!
Country [127]
0
0
China
Query!
State/province [127]
0
0
Beijing
Query!
Country [128]
0
0
China
Query!
State/province [128]
0
0
Shanghai
Query!
Country [129]
0
0
France
Query!
State/province [129]
0
0
Paris Cedex 15
Query!
Country [130]
0
0
United States of America
Query!
State/province [130]
0
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New Mexico
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Funding & Sponsors
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Summary
Brief summary
The purpose of this study is to test whether SU011248 has activity and is safe compared to interferon-alfa as first-line therapy in patients with metastatic renal cell carcinoma (RCC).
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Trial website
https://clinicaltrials.gov/study/NCT00098657
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Trial related presentations / publications
Rini BI, Hutson TE, Figlin RA, Lechuga MJ, Valota O, Serfass L, Rosbrook B, Motzer RJ. Sunitinib in Patients With Metastatic Renal Cell Carcinoma: Clinical Outcome According to International Metastatic Renal Cell Carcinoma Database Consortium Risk Group. Clin Genitourin Cancer. 2018 Aug;16(4):298-304. doi: 10.1016/j.clgc.2018.04.005. Epub 2018 May 4. de Velasco G, McKay RR, Lin X, Moreira RB, Simantov R, Choueiri TK. Comprehensive Analysis of Survival Outcomes in Non-Clear Cell Renal Cell Carcinoma Patients Treated in Clinical Trials. Clin Genitourin Cancer. 2017 Dec;15(6):652-660.e1. doi: 10.1016/j.clgc.2017.03.004. Epub 2017 Mar 21. Grunwald V, Lin X, Kalanovic D, Simantov R. Early Tumour Shrinkage: A Tool for the Detection of Early Clinical Activity in Metastatic Renal Cell Carcinoma. Eur Urol. 2016 Dec;70(6):1006-1015. doi: 10.1016/j.eururo.2016.05.010. Epub 2016 May 26. Grunwald V, McKay RR, Krajewski KM, Kalanovic D, Lin X, Perkins JJ, Simantov R, Choueiri TK. Depth of remission is a prognostic factor for survival in patients with metastatic renal cell carcinoma. Eur Urol. 2015 May;67(5):952-8. doi: 10.1016/j.eururo.2014.12.036. Epub 2015 Jan 7. Cella D, Michaelson MD, Bushmakin AG, Cappelleri JC, Charbonneau C, Kim ST, Li JZ, Motzer RJ. Health-related quality of life in patients with metastatic renal cell carcinoma treated with sunitinib vs interferon-alpha in a phase III trial: final results and geographical analysis. Br J Cancer. 2010 Feb 16;102(4):658-64. doi: 10.1038/sj.bjc.6605552. Epub 2010 Jan 26. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115-24. doi: 10.1056/NEJMoa065044. Guilhot F, Apperley J, Kim DW, Bullorsky EO, Baccarani M, Roboz GJ, Amadori S, de Souza CA, Lipton JH, Hochhaus A, Heim D, Larson RA, Branford S, Muller MC, Agarwal P, Gollerkeri A, Talpaz M. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Blood. 2007 May 15;109(10):4143-50. doi: 10.1182/blood-2006-09-046839. Epub 2007 Jan 30. Apperley JF, Cortes JE, Kim DW, Roy L, Roboz GJ, Rosti G, Bullorsky EO, Abruzzese E, Hochhaus A, Heim D, de Souza CA, Larson RA, Lipton JH, Khoury HJ, Kim HJ, Sillaber C, Hughes TP, Erben P, Van Tornout J, Stone RM. Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START a trial. J Clin Oncol. 2009 Jul 20;27(21):3472-9. doi: 10.1200/JCO.2007.14.3339. Epub 2009 Jun 1. Cortes J, Rousselot P, Kim DW, Ritchie E, Hamerschlak N, Coutre S, Hochhaus A, Guilhot F, Saglio G, Apperley J, Ottmann O, Shah N, Erben P, Branford S, Agarwal P, Gollerkeri A, Baccarani M. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood. 2007 Apr 15;109(8):3207-13. doi: 10.1182/blood-2006-09-046888. Epub 2006 Dec 21. Porkka K, Koskenvesa P, Lundan T, Rimpilainen J, Mustjoki S, Smykla R, Wild R, Luo R, Arnan M, Brethon B, Eccersley L, Hjorth-Hansen H, Hoglund M, Klamova H, Knutsen H, Parikh S, Raffoux E, Gruber F, Brito-Babapulle F, Dombret H, Duarte RF, Elonen E, Paquette R, Zwaan CM, Lee FY. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia. Blood. 2008 Aug 15;112(4):1005-12. doi: 10.1182/blood-2008-02-140665. Epub 2008 May 13. Hess G, Coiffier B, Crump M, Gisselbrecht C, Offner F, Romaguera J, Kang L, Moran PJ. Effect of prognostic classification on temsirolimus efficacy and safety in patients with relapsed or refractory mantle cell lymphoma: a retrospective analysis. Exp Hematol Oncol. 2015 Apr 11;4:11. doi: 10.1186/s40164-015-0006-1. eCollection 2015. Branford S, Yeung DT, Parker WT, Roberts ND, Purins L, Braley JA, Altamura HK, Yeoman AL, Georgievski J, Jamison BA, Phillis S, Donaldson Z, Leong M, Fletcher L, Seymour JF, Grigg AP, Ross DM, Hughes TP. Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline. Blood. 2014 Jul 24;124(4):511-8. doi: 10.1182/blood-2014-03-566323. Epub 2014 May 23. Branford S, Yeung DT, Ross DM, Prime JA, Field CR, Altamura HK, Yeoman AL, Georgievski J, Jamison BA, Phillis S, Sullivan B, Briggs NE, Hertzberg M, Seymour JF, Reynolds J, Hughes TP. Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML. Blood. 2013 May 9;121(19):3818-24. doi: 10.1182/blood-2012-10-462291. Epub 2013 Mar 20. Guilhot F, Hughes TP, Cortes J, Druker BJ, Baccarani M, Gathmann I, Hayes M, Granvil C, Wang Y. Plasma exposure of imatinib and its correlation with clinical response in the Tyrosine Kinase Inhibitor Optimization and Selectivity Trial. Haematologica. 2012 May;97(5):731-8. doi: 10.3324/haematol.2011.045666. Epub 2012 Feb 7. Chu SC, Tang JL, Li CC. Dasatinib in chronic myelogenous leukemia. N Engl J Med. 2006 Sep 7;355(10):1062-3; author reply 1063-4. No abstract available. Lilly MB, Ottmann OG, Shah NP, Larson RA, Reiffers JJ, Ehninger G, Muller MC, Charbonnier A, Bullorsky E, Dombret H, Brigid Bradley-Garelik M, Zhu C, Martinelli G. Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph-positive acute lymphoblastic leukemia who failed imatinib: Results from a phase 3 study. Am J Hematol. 2010 Mar;85(3):164-70. doi: 10.1002/ajh.21615. Kantarjian H, Cortes J, Kim DW, Dorlhiac-Llacer P, Pasquini R, DiPersio J, Muller MC, Radich JP, Khoury HJ, Khoroshko N, Bradley-Garelik MB, Zhu C, Tallman MS. Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up. Blood. 2009 Jun 18;113(25):6322-9. doi: 10.1182/blood-2008-11-186817. Epub 2009 Apr 15. Cortes J, Rousselot P, Kim DW, Ritchie E, Hamerschlak N, Coutre S, Hochhaus A, Guilhot F, Saglio G, Apperley J, Ottmann O, Shah N, Erben P, Branford S, Agarwal P, Gollerkeri A, Baccarani M. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood. 2007 Apr 15;109(8):3207-13. doi: 10.1182/blood-2006-09-046888. Epub 2006 Dec 21. Ottmann O, Dombret H, Martinelli G, Simonsson B, Guilhot F, Larson RA, Rege-Cambrin G, Radich J, Hochhaus A, Apanovitch AM, Gollerkeri A, Coutre S. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood. 2007 Oct 1;110(7):2309-15. doi: 10.1182/blood-2007-02-073528. Epub 2007 May 11. Porkka K, Koskenvesa P, Lundan T, Rimpilainen J, Mustjoki S, Smykla R, Wild R, Luo R, Arnan M, Brethon B, Eccersley L, Hjorth-Hansen H, Hoglund M, Klamova H, Knutsen H, Parikh S, Raffoux E, Gruber F, Brito-Babapulle F, Dombret H, Duarte RF, Elonen E, Paquette R, Zwaan CM, Lee FY. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia. Blood. 2008 Aug 15;112(4):1005-12. doi: 10.1182/blood-2008-02-140665. Epub 2008 May 13. Hochhaus A, Kantarjian HM, Baccarani M, Lipton JH, Apperley JF, Druker BJ, Facon T, Goldberg SL, Cervantes F, Niederwieser D, Silver RT, Stone RM, Hughes TP, Muller MC, Ezzeddine R, Countouriotis AM, Shah NP. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007 Mar 15;109(6):2303-9. doi: 10.1182/blood-2006-09-047266. Epub 2006 Nov 30. Erratum In: Blood. 2007 Sep 1;110(5):1438. Muller MC, Cortes JE, Kim DW, Druker BJ, Erben P, Pasquini R, Branford S, Hughes TP, Radich JP, Ploughman L, Mukhopadhyay J, Hochhaus A. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations. Blood. 2009 Dec 3;114(24):4944-53. doi: 10.1182/blood-2009-04-214221. Epub 2009 Sep 24.
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Results publications and other study-related documents
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Chu SC, Tang JL, Li CC. Dasatinib in chronic myelo...
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Results are available at
https://clinicaltrials.gov/study/NCT00098657
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