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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT02966782
Registration number
NCT02966782
Ethics application status
Date submitted
15/11/2016
Date registered
17/11/2016
Titles & IDs
Public title
A Study Evaluating Venetoclax Alone and in Combination With Azacitidine in Participants With Relapsed/Refractory Myelodysplastic Syndromes (MDS)
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Scientific title
A Phase 1b Study Evaluating the Safety and Pharmacokinetics of Venetoclax as a Single-Agent and in Combination With Azacitidine in Subjects With Relapsed/Refractory Myelodysplastic Syndromes
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Secondary ID [1]
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2016-001904-46
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Secondary ID [2]
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M15-522
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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:
Myelodysplastic Syndromes (MDS)
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Condition category
Condition code
Blood
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Haematological diseases
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Blood
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0
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Other blood disorders
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Other
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Research that is not of generic health relevance and not applicable to specific health categories listed above
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - venetoclax
Treatment: Drugs - azacitidine
Experimental: Venetoclax monotherapy (Cohort 1) -
Experimental: Venetoclax + azacitidine (Cohort 2) -
Experimental: Safety Expansion (Cohort 3) -
Treatment: Drugs: venetoclax
Tablet
Treatment: Drugs: azacitidine
Powder for injection, subcutaneously or intravenous
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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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AUCt for azacitidine
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Assessment method [1]
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Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for azacitidine
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Timepoint [1]
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Up to 32 days
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Primary outcome [2]
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Clearance (CL) for azacitidine
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Assessment method [2]
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Timepoint [2]
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Up to 32 days
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Primary outcome [3]
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Cmax for azacitidine
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Assessment method [3]
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Maximum plasma concentration (Cmax) of azacitidine
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Timepoint [3]
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Up to 32 days
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Primary outcome [4]
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Tmax for venetoclax
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Assessment method [4]
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Time to Cmax (peak time, Tmax) for venetoclax
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Timepoint [4]
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Up to 32 days
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Primary outcome [5]
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Recommended Phase 2 Dose (RPTD) and dosing schedules of venetoclax as monotherapy and in combination with azacitidine
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Assessment method [5]
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Timepoint [5]
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Measured from Day 1 until day 28 per dose level.
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Primary outcome [6]
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AUC[0 to infinity] for azacitidine
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Assessment method [6]
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Area under the plasma concentration-time curve from Time 0 to infinite time.
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Timepoint [6]
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Up to 32 days
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Primary outcome [7]
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Tmax for azacitidine
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Assessment method [7]
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Time to Cmax (peak time, Tmax) for azacitidine
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Timepoint [7]
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Up to 32 days
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Primary outcome [8]
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AUC [0-24] for venetoclax
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Assessment method [8]
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AUC over a 24-hour dose interval (AUC\[0-24\]) for venetoclax
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Timepoint [8]
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Up to 32 days
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Primary outcome [9]
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AUCt for venetoclax
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Assessment method [9]
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Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for venetoclax
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Timepoint [9]
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Up to 32 days
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Primary outcome [10]
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Cmax of venetoclax
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Assessment method [10]
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Maximum plasma concentration (Cmax) of venetoclax
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Timepoint [10]
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Up to 32 days
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Primary outcome [11]
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Half-life (t[1/2]) for azacitidine
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Assessment method [11]
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Terminal elimination half-life (t\[1/2\]) for azacitidine
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Timepoint [11]
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Up to 32 days
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Primary outcome [12]
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Number of Participants With Adverse Events (AEs)
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Assessment method [12]
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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. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
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Timepoint [12]
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Up to Maximum of 24 months
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Secondary outcome [1]
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Event-Free Survival (EFS)
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Assessment method [1]
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Timepoint [1]
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Measured from the date of the first dose of study drug to date of earliest disease progression, death, or initiation of new non-protocol-specified anti-MDS therapy without documented progression, and for up to 5 years after the last subject is enrolled.
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Secondary outcome [2]
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Overall Survival (OS)
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Assessment method [2]
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Timepoint [2]
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Measured from the date of first dose of study drug to the date of death, and for up to 5 years after the last subject is enrolled.
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Secondary outcome [3]
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Rate of Modified Overall Response (mORR)
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Assessment method [3]
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Proportion of participants with a mORR using best outcome will be calculated.
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Timepoint [3]
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Measured from Cycle 1 Day 1 (C1D1) as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
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Secondary outcome [4]
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Time to next treatment (TTNT)
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Assessment method [4]
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Timepoint [4]
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Measured from first dose of study drug to start of new non-protocol specified MDS therapy, and for up to 5 years after the last subject is enrolled.
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Secondary outcome [5]
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Duration of mORR
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Assessment method [5]
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Defined as the number of days from the date of first response (CR, mCR or PR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier..
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Timepoint [5]
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Measured from the date of first response (CR, mCR or PR) to the earliest documentation of progressive disease (PD), and for an anticipated maximum duration of 24 months.
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Secondary outcome [6]
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Rate of platelet (PLT) transfusion independence
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Assessment method [6]
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Proportion of participants who become platelet transfusion-independent
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Timepoint [6]
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Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
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Secondary outcome [7]
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Time to Transformation acute myeloid leukemia (AML)
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Assessment method [7]
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Defined as blast count greater than or equal to 20% in either peripheral blood or bone marrow.
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Timepoint [7]
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Measured from the date of first dose of study drug to the date of documented AML transformation for an anticipated maximum duration of 24 months.
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Secondary outcome [8]
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Progression-Free Survival (PFS)
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Assessment method [8]
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Timepoint [8]
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Measured from the date of the first dose of study drug to the date of earliest disease progression or death, and for an anticipated maximum duration of 24 months.
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Secondary outcome [9]
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Overall Response Rate (ORR)
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Assessment method [9]
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ORR (equals the sum of rates of complete remission \[CR\] + marrow complete remission (mCR) + partial remission \[PR\]) of venetoclax as a single-agent and in combination with azacitidine.
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Timepoint [9]
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Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
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Secondary outcome [10]
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Complete Remission (CR) Rate
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Assessment method [10]
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Proportion of subjects who achieved a complete remission.
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Timepoint [10]
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Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
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Secondary outcome [11]
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Rate of red blood cell (RBC) transfusion independence
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Assessment method [11]
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Proportion of red blood cell (RBC) transfusion independence.
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Timepoint [11]
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Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
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Secondary outcome [12]
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Duration of Complete Response (CR)
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Assessment method [12]
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Duration of CR will be defined as the number of days from the date of first response CR to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier.
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Timepoint [12]
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Measured from date of first response (CR) to the to the earliest documentation of progressive disease or death of any cause, and for an anticipated maximum duration of 24 months.
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Secondary outcome [13]
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Rate of Hematologic Improvement (HI)
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Assessment method [13]
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Proportion of participants with HI (erythroid/platelet/neutrophil responses)
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Timepoint [13]
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Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
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Secondary outcome [14]
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Rate of marrow complete remission (mCR)
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Assessment method [14]
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Proportion of participants with marrow complete remission with or without hematological improvement.
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Timepoint [14]
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Measured from Cycle 1 Day 1 (C1D1) as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
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Secondary outcome [15]
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Duration of ORR
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Assessment method [15]
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Duration of response (ORR) will be defined as the number of days from the date of first response (CR or PR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier.
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Timepoint [15]
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Measured from the date of first response (CR or PR) to the earliest documentation of progressive disease or death of any cause, and for an anticipated maximum duration of 24 months.
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Eligibility
Key inclusion criteria
* Subjects who have relapsed or refractory MDS.
* Subject enrolled in venetoclax monotherapy must have documented failure of prior therapy with a hypomethylating agent (HMA). HMA-failure is defined as:
1. Relapse after initial complete or partial response or hematological improvement after at least 4 cycles of azacitidine or at least 4 cycles of decitabine within the last 5 years, OR
2. Failure to achieve complete or partial response or hematological improvement after at least 4 cycles of azacitidine or at least 4 cycles of decitabine within the last 5 years
* Subjects must have presence of < 20% bone marrow blasts per bone marrow biopsy/aspirate at screening.
* Subject is not a candidate to undergo allogenic hematopoietic stem cell transplantation (HSCT).
* Subject must have an Eastern Cooperative Oncology Group (ECOG) performance score of =2.
* Subject must have adequate hematologic, renal, and hepatic function.
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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
* Subject has received prior therapy with a BH3 mimetic.
* Subject has MDS evolving from a pre-existing myeloproliferative neoplasm (MPN).
* Subject has MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN.
* Subject has received allogeneic HSCT or solid organ transplantation.
* Subject has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug.
* Subject is pregnant or breastfeeding.
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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
Parallel
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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
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
7/03/2017
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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
5/04/2023
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Sample size
Target
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Accrual to date
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Final
70
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Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
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Recruitment hospital [1]
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St George Hospital /ID# 156037 - Kogarah
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Recruitment hospital [2]
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Liverpool Hospital /ID# 155952 - Liverpool
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Recruitment hospital [3]
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St Vincent's Hospital Melbourne /ID# 155950 - Fitzroy Melbourne
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Recruitment hospital [4]
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The Royal Melbourne Hospital /ID# 155949 - Parkville
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Recruitment hospital [5]
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Royal Perth Hospital /ID# 155951 - Perth
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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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2170 - Liverpool
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Recruitment postcode(s) [3]
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3065 - Fitzroy Melbourne
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Recruitment postcode(s) [4]
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3050 - Parkville
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Recruitment postcode(s) [5]
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6000 - Perth
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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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Arizona
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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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Colorado
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Country [3]
0
0
United States of America
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State/province [3]
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0
Connecticut
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Country [4]
0
0
United States of America
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State/province [4]
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Illinois
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Country [5]
0
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United States of America
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State/province [5]
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Massachusetts
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Country [6]
0
0
United States of America
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State/province [6]
0
0
New York
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Country [7]
0
0
United States of America
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State/province [7]
0
0
Oregon
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Country [8]
0
0
United States of America
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State/province [8]
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Texas
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Country [9]
0
0
Germany
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State/province [9]
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Baden-Wuerttemberg
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Country [10]
0
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Germany
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State/province [10]
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Nordrhein-Westfalen
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Country [11]
0
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Germany
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State/province [11]
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0
Sachsen
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Country [12]
0
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Germany
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State/province [12]
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Dresden
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Country [13]
0
0
Germany
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State/province [13]
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Halle (Saale)
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Country [14]
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Germany
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State/province [14]
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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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Country
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Other collaborator category [1]
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Other
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Name [1]
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Celgene; Genentech, Inc.
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Address [1]
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0
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Country [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a Phase 1b, open-label, multicenter study designed to evaluate the safety and pharmacokinetics of venetoclax as a single-agent and in combination with azacitidine in participants with relapsed/refractory Myelodysplastic Syndromes (MDS).
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Trial website
https://clinicaltrials.gov/study/NCT02966782
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Trial related presentations / publications
Franke GN, Luckemeier P, Platzbecker U. Allogeneic Stem-Cell Transplantation in Patients With Myelodysplastic Syndromes and Prevention of Relapse. Clin Lymphoma Myeloma Leuk. 2021 Jan;21(1):1-7. doi: 10.1016/j.clml.2020.10.008. Epub 2020 Oct 16.
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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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0
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Phone
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0
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Fax
0
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Email
0
0
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Contact person for public queries
Name
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Address
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Country
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0
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Phone
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0
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Fax
0
0
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Email
0
0
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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/NCT02966782