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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT00481091
Registration number
NCT00481091
Ethics application status
Date submitted
30/05/2007
Date registered
1/06/2007
Date last updated
13/06/2023
Titles & IDs
Public title
A Study of ABT-263 in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia
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Scientific title
A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics, and Efficacy of ABT-263 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia
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Secondary ID [1]
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2007-002143-25
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Secondary ID [2]
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M06-873
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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:
Chronic Lymphocytic Leukemia
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Condition category
Condition code
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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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - ABT-263
Experimental: Navitoclax 14/21 Day Cycle: 10 mg - Navitoclax 10 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle.
Experimental: Navitoclax 14/21 Day Cycle: 110 mg - Navitoclax 110 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle.
Experimental: Navitoclax 14/21 Day Cycle: 200 mg - Navitoclax 200 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle.
Experimental: Navitoclax 14/21 Day Cycle: 250 mg - Navitoclax 250 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle.
Experimental: Navitoclax 21/21 Day Cycle: 125 mg - Navitoclax 125 mg administered for 21 consecutive days to complete a 21-day cycle.
Experimental: Navitoclax 21/21 Day Cycle: 200 mg - Navitoclax 200 mg administered for 21 consecutive days to complete a 21-day cycle.
Experimental: Navitoclax 21/21 Day Cycle: 250 mg - Navitoclax 250 mg administered for 21 consecutive days to complete a 21-day cycle.
Experimental: Navitoclax 21/21 Day Cycle: 300 mg - Navitoclax 300 mg administered for 21 consecutive days to complete a 21-day cycle.
Experimental: Phase 2: Navitoclax 100 mg - Navitoclax 100 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s).
Experimental: Phase 2: Navitoclax 250 mg - Navitoclax 250 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s).
Treatment: Drugs: ABT-263
Tablet; Oral
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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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Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to Adverse Events (AEs)
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Assessment method [1]
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An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An SAE is one that: results in death, hospitalization, prolongation of hospitalization, or persistent or significant disability/incapacity; is life-threatening, a congenital anomaly, or other important medical event. Events were graded as 1=mild, 2=moderate, 3=severe, 4=life-threatening, or 5=death. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A treatment-emergent adverse event is defined as any adverse event with onset or worsening reported by a subject from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug administration. Deaths category included non treatment emergent deaths.
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Timepoint [1]
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From first dose of study drug to 30 days post-last dose. Participants enrolled in the 14/21-day cycle received a mean of 21.7 treatment cycles; participants enrolled in the 21/21-day cycle received a mean of 19.4 treatment cycles.
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Primary outcome [2]
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Phase 1: Number of Participants With DLTs in the Dose Escalation Phase
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Assessment method [2]
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DLTs were graded according to NCI CTCAE version 3.0 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life threatening; grade 5=death). Any of the following events, considered possibly or probably related to the administration of navitoclax, were considered a DLT: Grade 4 thrombocytopenia (< 25,000/mm^3); platelet counts < 25,000/mm^3, Grade 2 or higher bleeding associated with thrombocytopenia; all other Grade 3, 4 or 5 adverse events were considered a DLT. Exceptions included: Grade 3, 4 febrile neutropenia less than 7 days; Grade 3, 4 leukopenia; Grade 3, 4 lymphopenia; Grade 3 nausea, vomiting and/or diarrhea unless unresponsive to treatment; Grade 2 toxicity that requires dose modification or delay of > 1 week.
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Timepoint [2]
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Cycle 1 (Up to 21 days) plus 7 days
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Primary outcome [3]
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Phase 1: Maximum Tolerated Dose (MTD) in the Dose Escalation Phase
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Assessment method [3]
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The MTD was defined as the dose at which 30% of participants experienced a DLT during the first cycle. DLTs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life threatening; grade 5=death). Any of the following events, considered possibly or probably related to the administration of navitoclax, were considered a DLT: Grade 4 thrombocytopenia (< 25,000/mm^3); platelet counts < 25,000/mm^3, Grade 2 or higher bleeding associated with thrombocytopenia; all other Grade 3, 4 or 5 adverse events were considered a DLT. Exceptions included: Grade 3, 4 febrile neutropenia less than 7 days; Grade 3, 4 leukopenia; Grade 3, 4 lymphopenia; Grade 3 nausea, vomiting and/or diarrhea unless unresponsive to treatment; Grade 2 toxicity that requires dose modification or delay of > 1 week.
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Timepoint [3]
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Cycle 1 (Up to 21 days) plus 7 days
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Primary outcome [4]
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Phase 1: Recommended Phase 2 Dose (RPTD) Determined in the Dose Escalation Phase
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Assessment method [4]
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The RPTD was determined based on observed DLTs and/or determination of the MTD in phase 1. (See Outcome Measures 2 and 3 above for definition of DLT and MTD.)
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Timepoint [4]
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Cycle 1 (Up to 21 days) plus 7 days
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Primary outcome [5]
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Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Navitoclax
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Assessment method [5]
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Timepoint [5]
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Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
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Primary outcome [6]
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Phase 1: Maximum Observed Plasma Concentration (Cmax)
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Assessment method [6]
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Timepoint [6]
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Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
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Primary outcome [7]
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Phase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 8 (AUC8)
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Assessment method [7]
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Timepoint [7]
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Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
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Primary outcome [8]
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Phase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 24 (AUC24)
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Assessment method [8]
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The AUC24 was derived and reported from Cycle 1 Day 1 values and Cycle 1 Day 14 values; the pre-dose value taken on Day 14 was utilized as 24-hour timepoint on Day 14 to generate AUC24 for Day 14.
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Timepoint [8]
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Cycle 1 Day 1: pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Cycle 1 Days 14: pre-dose, 2, 4, 6, 8
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Primary outcome [9]
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Phase 1: Cmax/Dose
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Assessment method [9]
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Timepoint [9]
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Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
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Primary outcome [10]
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Phase 1: AUC8/Dose
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Assessment method [10]
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Timepoint [10]
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Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
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Primary outcome [11]
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Phase 1: AUC24/Dose
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Assessment method [11]
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The AUC24 was derived and reported from Cycle 1 Day 1 values and Cycle 1 Day 14 values; the pre-dose value taken on Day 14 was utilized as 24-hour timepoint on Day 14 to generate AUC24 for Day 14.
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Timepoint [11]
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Cycle 1 Day 1: pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Cycle 1 Days 14: pre-dose, 2, 4, 6, 8
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Primary outcome [12]
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Phase 1: Terminal Phase Elimination Rate Constant (ß) for Navitoclax
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Assessment method [12]
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Timepoint [12]
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Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose
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Primary outcome [13]
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Phase 1: Terminal Phase Elimination Half-life (t1/2) of Navitoclax
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Assessment method [13]
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For t1/2, the harmonic mean and psuedo-standard deviation are used.
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Timepoint [13]
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Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose
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Primary outcome [14]
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Phase 2: Number of Participants With TEAEs, SAEs, and Discontinuations Due to AEs
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Assessment method [14]
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An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An SAE is one that: results in death, hospitalization, prolongation of hospitalization, or persistent or significant disability/incapacity; is life-threatening, a congenital anomaly, or other important medical event. Events were graded as 1=mild, 2=moderate, 3=severe, 4=life-threatening, or 5=death. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A treatment-emergent adverse event is defined as any adverse event with onset or worsening reported by a subject from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug administration. Deaths category included non treatment emergent deaths.
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Timepoint [14]
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From first dose of study drug to 30 days post-last dose. Participants enrolled in Phase 2 received a mean of 15.6 treatment cycles.
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Primary outcome [15]
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Phase 2: Dose-Normalized Plasma Concentrations After Navitoclax Once Daily Dosing
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Assessment method [15]
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Timepoint [15]
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Cycle 1 Day 1: 4-8 h postdose; Cycle 1 Day 15: predose; Cycle 3 Day 1: predose, 4-8 h postdose; Cycle 5 Day 1: predose, 4-8 h postdose; Cycle 7 Day 1: predose, 4-8 h postdose; Cycle 9 Day 1: predose, 4-8 h postdose
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Eligibility
Key inclusion criteria
- Relapsed or refractory CLL and require treatment in opinion of investigator.
- Eastern Cooperative Oncology Group (ECOG) <= 1.
- Adequate bone marrow independent of growth factor support, renal and hepatic function
per defined laboratory criteria.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- History or is clinically suspicious for cancer-related Central Nervous System disease.
- Receipt of allogenic or autologous stem cell transplant.
- Recent history (within 1 year of first dose) of underlying, predisposing condition of
bleeding or currently exhibits signs of bleeding.
- Active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis.
- Active immune thrombocytopenic purpura or history of being refractory to platelet
transfusions (within 1 year of first dose).
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Other
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
25/07/2007
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
12/05/2022
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Sample size
Target
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Accrual to date
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Final
60
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Peter MacCallum Cancer Ctr /ID# 6583 - Melbourne
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Recruitment hospital [2]
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The Royal Melbourne Hospital /ID# 5576 - Parkville
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Recruitment postcode(s) [1]
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3000 - Melbourne
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Recruitment postcode(s) [2]
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3050 - Parkville
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Massachusetts
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Country [3]
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United States of America
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State/province [3]
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Nebraska
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Country [4]
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United States of America
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State/province [4]
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New York
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Country [5]
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United States of America
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State/province [5]
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Texas
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Country [6]
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United States of America
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State/province [6]
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Washington
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Country [7]
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Germany
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State/province [7]
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Nordrhein-Westfalen
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Country [8]
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United Kingdom
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State/province [8]
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England
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
AbbVie
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Address
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Country
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Other collaborator category [1]
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Commercial sector/Industry
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Name [1]
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Genentech, Inc.
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Address [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
The Phase 1 portion of the study will evaluate the pharmacokinetic profile and safety of
ABT-263 under two different dosing schedules with the objective of defining the dose limiting
toxicity and maximum tolerated dose. The Phase 2a portion of the study will evaluate ABT-263
at the defined recommended Phase 2 dose to obtain additional safety information and a
preliminary assessment of efficacy. The Extension Study portion will allow active subjects to
continue to receive ABT-263 for up to 11 years after the last subject transitions with less
frequent study evaluations.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT00481091
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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ABBVIE INC.
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Address
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AbbVie
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT00481091
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