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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT02203773
Registration number
NCT02203773
Ethics application status
Date submitted
10/07/2014
Date registered
30/07/2014
Titles & IDs
Public title
Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)
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Scientific title
A Phase 1b Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine in Treatment-Naive Subjects With Acute Myelogenous Leukemia Who Are Greater Than or Equal to 60 Years of Age and Who Are Not Eligible for Standard Induction Therapy
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Secondary ID [1]
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2014-000687-18
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Secondary ID [2]
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M14-358
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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:
Acute Myelogenous Leukemia
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Myelogenous Leukemia
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Treatment Naive AML
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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(has expanded access)
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Description of intervention(s) / exposure
Treatment: Drugs - Posaconazole
Treatment: Drugs - ABT-199
Treatment: Drugs - Decitabine
Treatment: Drugs - Azacitidine
Experimental: ABT-199 + Azacitidine - Treatment Naive Acute Myelogenous Leukemia
Experimental: ABT-199 + Decitabine - Treatment Naive Acute Myelogenous Leukemia
Experimental: ABT-199+Decitabine+Posaconazole - Treatment Naive Acute Myelogenous Leukemia
Treatment: Drugs: Posaconazole
Posaconazole will be administered orally twice a day on Cycle 1 Day 21 and once daily from Cycle 1 Day 22 to Cycle 1 Day 28.
Treatment: Drugs: ABT-199
ABT-199 is taken orally once daily starting on Day 2 of cycle 1 and begin on day 1 of every other cycle thereafter. This is a dose escalation study, therefore the dose of ABT-199 will change.
Treatment: Drugs: Decitabine
Decitabine will be administered by IV infusion over 1 hour beginning on Day 1 thru Day 5 of each Cycle for a minimum of 4 Cycles
Treatment: Drugs: Azacitidine
Azacitidine will be administered by IV infusion over 10 to 40 minutes or subcutaneously based on the institutional guidelines, beginning on Day 1 through Day 7 of each Cycle, for a minimum of 4 Cycles.
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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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Number of Participants Experiencing Adverse Events (AEs)
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Assessment method [1]
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An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug.
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Timepoint [1]
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Measured up to 1 year after the last subject last dose
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Primary outcome [2]
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Maximum observed plasma concentration (Cmax)
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Assessment method [2]
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Maximum observed concentration, occurring at Tmax.
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Timepoint [2]
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For approximately 5 days following a single dose of ABT-199.
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Primary outcome [3]
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Time to Cmax (peak time, Tmax),
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Assessment method [3]
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The time at which maximum plasma concentration (Cmax) is observed.
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Timepoint [3]
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For approximately 5 days following a single dose of ABT-199.
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Primary outcome [4]
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The area under the plasma concentration-time curve (AUC) from 0 to 24 hours (AUC0-24)
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Assessment method [4]
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The area under the plasma concentration-time curve (AUC) over a 24-hour dose interval.
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Timepoint [4]
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For approximately 5 days following a single dose of ABT-199.
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Primary outcome [5]
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Half-Life (t1/2)
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Assessment method [5]
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The time required for the concentration of the drug to reach half of its original value.
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Timepoint [5]
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For approximately 5 days following a single dose of ABT-199.
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Primary outcome [6]
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Clearance (CL)
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Assessment method [6]
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Clearance is defined as the rate at which drug is cleared from the blood.
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Timepoint [6]
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For approximately 5 days following a single dose of ABT-199.
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Primary outcome [7]
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Complete Remission Rate
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Assessment method [7]
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Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission.
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Timepoint [7]
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Measured up to 1 year after the last subject last dose
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Primary outcome [8]
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Complete Remission with incomplete blood count recovery rate
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Assessment method [8]
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Complete Remission with incomplete blood count recovery rate will be determined by the number of subjects who achieve a Complete Remission with incomplete blood count recovery.
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Timepoint [8]
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Measured up to 1 year after the last subject last dose
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Primary outcome [9]
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Overall Response Rate
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Assessment method [9]
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Overall response rate will be defined as the proportion of subjects who achieve a complete remission (CR), complete remission incomplete (CRi), or partial remission (PR) per the International Working Group criteria for AML.
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Timepoint [9]
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Measured up to 1 year after the last subject last dose
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Primary outcome [10]
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Overall Survival
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Assessment method [10]
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Overall survival will be defined as the number of days from the date of first dose to the date of death.
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Timepoint [10]
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Measured up to 1 year after the last subject last dose
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Secondary outcome [1]
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Event Free Survival
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Assessment method [1]
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Event-free survival (EFS) will be defined as the number of days from the date of first dose to the date of earliest evidence of relapse, subsequent treatment other than stem cell transplant while in composite complete response (CR + CRi), or death.
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Timepoint [1]
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Measured up to 1 year after the last subject last dose
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Secondary outcome [2]
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Duration of Response
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Assessment method [2]
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Duration of response will be defined as the number of days from the date of first response per the IWG criteria for AML to the earliest recurrence or progressive disease (PD).
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Timepoint [2]
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Measured up to 1 year after the last subject last dose
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Eligibility
Key inclusion criteria
* Subjects must have confirmation of Acute Myeloid Leukemia (AML) by WHO criteria and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
* Subject must have received no prior treatment for AML with the exception of hydroxyurea
* Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 for subjects greater than or equal to 75 years of age, or 0 to 3 for subjects greater than or equal to 60 to 74 years of age
* Subject must have adequate kidney and liver function as described in the protocol
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Minimum age
60
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
* Subject has received treatment with the following hypomethylating agent and/or chemo therapeutic agent for for an antecedent hematologic disorder (AHD) (Subjects may have been treated with other agents for AHD i.e., Myelodysplastic syndrome [MDS])
* Subject has history of Myeloproliferative Neoplasm (MPN).
* Subject has favorable risk cytogenetics as categorized by the National Comprehensive Cancer Network Guidelines Version 2, 2014 for AML.
* Subject has t(8;21), inv(16), t(16;16) or t(15;17) karyotype abnormalities.
* Subject has acute promyelocytic leukemia.
* Subject has known active central nervous system involvement with AML.
* Subject has received a strong and/or moderate CYP3A inducer within 7 days prior to the initiation of study treatment.
* Subject has a history of other malignancies prior to study entry, with the exception of:
* Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
* Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
* Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
* Subject has a white blood cell count > 25 × 10^9/L. Note: Hydroxyurea is permitted to meet this criterion.
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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
Single group
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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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
6/10/2014
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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
16/06/2022
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Sample size
Target
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Accrual to date
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Final
212
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Recruitment in Australia
Recruitment state(s)
NSW,VIC
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Recruitment hospital [1]
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St George Hospital /ID# 130356 - Kogarah
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Recruitment hospital [2]
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Peter MacCallum Cancer Ctr /ID# 130352 - Melbourne
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Recruitment hospital [3]
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Alfred Health /ID# 130353 - Melbourne
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Recruitment postcode(s) [1]
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2217 - Kogarah
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Recruitment postcode(s) [2]
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3000 - Melbourne
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Recruitment postcode(s) [3]
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3004 - Melbourne
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Recruitment outside Australia
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United States of America
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State/province [1]
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California
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United States of America
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State/province [2]
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Colorado
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United States of America
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Georgia
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United States of America
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Illinois
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Texas
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United States of America
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Washington
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France
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State/province [11]
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Gironde
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France
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Haute-Garonne
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France
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Paris
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Germany
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Baden-Wuerttemberg
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Germany
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Sachsen
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Germany
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Dresden
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Germany
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Munich
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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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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
This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered venetoclax (ABT-199) combined with decitabine or azacitidine and the preliminary efficacy of these combinations. In addition, there is a drug-drug interaction (DDI) sub-study only at a single site, to assess the pharmacokinetics and safety of venetoclax (ABT-199) in combination with posaconazole.
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Trial website
https://clinicaltrials.gov/study/NCT02203773
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Trial related presentations / publications
Badawi M, Chen X, Marroum P, Suleiman AA, Mensing S, Koenigsdorfer A, Schiele JT, Palenski T, Samineni D, Hoffman D, Menon R, Salem AH. Bioavailability Evaluation of Venetoclax Lower-Strength Tablets and Oral Powder Formulations to Establish Interchangeability with the 100 mg Tablet. Clin Drug Investig. 2022 Aug;42(8):657-668. doi: 10.1007/s40261-022-01172-4. Epub 2022 Jul 13. Konopleva M, Thirman MJ, Pratz KW, Garcia JS, Recher C, Pullarkat V, Kantarjian HM, DiNardo CD, Dail M, Duan Y, Chyla B, Potluri J, Miller CL, Wei AH. Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naive Acute Myeloid Leukemia. Clin Cancer Res. 2022 Jul 1;28(13):2744-2752. doi: 10.1158/1078-0432.CCR-21-3405. Pollyea DA, DiNardo CD, Arellano ML, Pigneux A, Fiedler W, Konopleva M, Rizzieri DA, Smith BD, Shinagawa A, Lemoli RM, Dail M, Duan Y, Chyla B, Potluri J, Miller CL, Kantarjian HM. Impact of Venetoclax and Azacitidine in Treatment-Naive Patients with Acute Myeloid Leukemia and IDH1/2 Mutations. Clin Cancer Res. 2022 Jul 1;28(13):2753-2761. doi: 10.1158/1078-0432.CCR-21-3467. DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. doi: 10.1182/blood-2018-08-868752. Epub 2018 Oct 25. DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. doi: 10.1016/S1470-2045(18)30010-X. Epub 2018 Jan 12. Agarwal SK, DiNardo CD, Potluri J, Dunbar M, Kantarjian HM, Humerickhouse RA, Wong SL, Menon RM, Konopleva MY, Salem AH. Management of Venetoclax-Posaconazole Interaction in Acute Myeloid Leukemia Patients: Evaluation of Dose Adjustments. Clin Ther. 2017 Feb;39(2):359-367. doi: 10.1016/j.clinthera.2017.01.003. Epub 2017 Feb 1.
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Public notes
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Contacts
Principal investigator
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ABBVIE INC.
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Address
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AbbVie
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Contact person for public queries
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT02203773