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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/NCT02942290
Registration number
NCT02942290
Ethics application status
Date submitted
18/10/2016
Date registered
24/10/2016
Date last updated
26/01/2023
Titles & IDs
Public title
A Study Evaluating Venetoclax in Combination With Azacitidine in Participants With Treatment-Naïve Higher-Risk Myelodysplastic Syndromes (MDS)
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Scientific title
A Phase 1b Dose Escalation Study Evaluating the Safety and Pharmacokinetics of Venetoclax in Combination With Azacitidine in Subjects With Treatment-Naïve Higher-Risk Myelodysplastic Syndromes (MDS)
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Secondary ID [1]
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2016-001657-41
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Secondary ID [2]
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M15-531
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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 - Azacitidine
Treatment: Drugs - Venetoclax
Experimental: Venetoclax + Azacitidine -
Treatment: Drugs: Azacitidine
Powder for injection; taken subcutaneously (SC) or intravenous (IV); Administered on Days 1-7 of 28 days cycle or Days 1-5 of Week 1 & Days 1-2 of Week 2 of 28 day cycle.
Treatment: Drugs: Venetoclax
Oral; Tablet
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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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Cmax of venetoclax
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Assessment method [2]
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Maximum plasma concentration (Cmax) of venetoclax.
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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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AUCt for venetoclax
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Assessment method [3]
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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 [3]
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0
Up to 32 days
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Primary outcome [4]
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0
Tmax of venetoclax
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Assessment method [4]
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Time to Cmax (peak time, Tmax) of venetoclax.
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Timepoint [4]
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0
Up to 32 days
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Primary outcome [5]
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0
AUC[0 to infinity] for azacitidine
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Assessment method [5]
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Area under the plasma concentration-time curve from Time 0 to infinite time.
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Timepoint [5]
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Up to 32 days
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Primary outcome [6]
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Recommended Phase 2 dose (RPTD) and dosing schedule of venetoclax in combination with azacitidine
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Assessment method [6]
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The RPTD of venetoclax [co-administered venetoclax and azacitidine] will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data [upon completion of the dose escalation phase].
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Timepoint [6]
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Measured from Day 1 until Day 28 per dose level.
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Primary outcome [7]
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Half-life (t[1/2]) for azacitidine
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Assessment method [7]
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Terminal elimination half-life (t[1/2]) for azacitidine.
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Timepoint [7]
0
0
Up to 32 days
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Primary outcome [8]
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0
Cmax for azacitidine
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Assessment method [8]
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Maximum plasma concentration (Cmax) of azacitidine.
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Timepoint [8]
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0
Up to 32 days
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Primary outcome [9]
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0
AUC[0-24] for venetoclax
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Assessment method [9]
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AUC over a 24-hour dose interval (AUC[0-24]) for venetoclax.
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Timepoint [9]
0
0
Up to 32 days
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Primary outcome [10]
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Clearance (CL) for azacitidine
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Assessment method [10]
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Clearance is defined as the volume of plasma cleared of the drug per unit time.
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Timepoint [10]
0
0
Up to 32 days
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Primary outcome [11]
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0
Tmax for azacitidine
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Assessment method [11]
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0
Time to Cmax (peak time, Tmax) of azacitidine.
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Timepoint [11]
0
0
Up to 32 days
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Primary outcome [12]
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0
Complete Remission (CR) Rate
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Assessment method [12]
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0
Complete remission rate will be defined as the proportion of participants who achieved a complete response per the International Working Group (IWG) 2006 criteria for Myelodysplastic Syndromes (MDS).
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Timepoint [12]
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0
Measured from Cycle 1 Day 1 as long as the participant 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 [1]
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Rate of red blood cell (RBC) transfusion independence
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Assessment method [1]
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Percentages of participants who become RBC transfusion-independent.
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Timepoint [1]
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0
Measured from Cycle 1 Day 1 as long as the participant 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 [2]
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Progression-Free Survival (PFS)
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Assessment method [2]
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PFS is defined as the number of days from the date of the first dose of study drug to the date of earliest disease progression or death due to disease progression or febrile neutropenia.
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Timepoint [2]
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Measured from the date of first dose of study drug to the date of earliest disease progression or death due to disease progression or febrile neutropenia, and for an anticipated maximum duration of 24 months.
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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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OS is defined as number of days from the date of first dose of the study drug to the date of death of any cause.
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Timepoint [3]
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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 participant is enrolled.
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Secondary outcome [4]
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Hematologic Improvement (HI) rate
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Assessment method [4]
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Percentages of participants with HI (erythroid/platelet/neutrophil responses).
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Timepoint [4]
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Measured from Cycle 1 Day 1 as long as the participant 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 [5]
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0
Rate of platelet (PLT) transfusion independence
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Assessment method [5]
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0
Percentages of participants who become platelet transfusion-independent.
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Timepoint [5]
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0
Measured from Cycle 1 Day 1 as long as the participant 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 [6]
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Event-Free Survival (EFS)
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Assessment method [6]
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Event-free survival (EFS) will be defined as the number of days from the date of the first dose of study drug to the date of earliest disease progression or death of any cause.
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Timepoint [6]
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0
Measured from the date of the first dose of study drug to the date of earliest disease progression, death of any cause and for up to 5 yrs after the last participant is enrolled
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Secondary outcome [7]
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Time to transformation to acute myeloid leukemia (AML)
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Assessment method [7]
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Defined as the number of days from the date of the first dose of study drug to the date of documented AML transformation.
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Timepoint [7]
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Measured from the date of first dose of study drug to date of documented AML transformation, defined as the presence of blast count greater than or equal to 20% in either peripheral blood or bone marrow for an anticipated maximum duration of 24 months.
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Secondary outcome [8]
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Overall Response Rate (ORR)
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Assessment method [8]
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ORR (equals the rates of complete remission [CR] + partial remission [PR]) of venetoclax in combination with azacitidine.
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Timepoint [8]
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Measured from Cycle 1 Day 1 as long as the participant 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 [9]
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Time to next treatment (TTNT)
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Assessment method [9]
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Time to next treatment (TTNT) will be defined as the time from the first dose of study drug to start of new non-protocol specified MDS therapy or death from any cause.
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Timepoint [9]
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Measured from the first dose of study drug to start of new non-protocol specified MDS therapy, and for up to 5 years after the last participant is enrolled.
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Secondary outcome [10]
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Marrow Complete Remission (mCR) Rate
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Assessment method [10]
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Defined as the proportion of participants who achieved a marrow complete response with or without hematological improvement per the International Working Group (IWG) 2006 criteria for Myelodysplastic Syndromes.
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Timepoint [10]
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0
Measured from Cycle 1 Day 1 as long as the participant 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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Modified Overall Response Rate (mORR)
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Assessment method [11]
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mORR (equals CR + PR + mCR) of venetoclax in combination with azacitidine.
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Timepoint [11]
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0
Measured from Cycle 1 Day 1 as long as the participant 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 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]
0
0
Measured from Cycle 1 Day 1 as long as the participant 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 [13]
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Duration of mORR
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Assessment method [13]
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0
Duration of response (mORR) will be defined as the number of days from the date of first response (CR, PR or mCR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier.
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Timepoint [13]
0
0
Measured from Cycle 1 Day 1 as long as the participant 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]
0
0
Duration of ORR
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Assessment method [14]
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0
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 [14]
0
0
Measured from Cycle 1 Day 1 as long as the participant 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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Rate of AML transformation
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Assessment method [15]
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The AML transformation rate is defined as the proportion of participants transformed to Acute Myelogenous Leukemia.
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Timepoint [15]
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Measured from the date of first dose of study drug to date of documented AML transformation, defined as the presence of blast count greater than or equal to 20% in either peripheral blood or bone marrow for an anticipated maximum duration of 24 months.
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Secondary outcome [16]
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Time to First Response (CR)
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Assessment method [16]
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Time to first response (CR) will be defined as the number of days from the date of first dose of the study drug to the date of the first response of CR.
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Timepoint [16]
0
0
Measured from Cycle 1 Day 1 as long as the participant 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 [17]
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0
Time to First Response (mORR)
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Assessment method [17]
0
0
Time to first response (mORR) will be defined as the number of days from the date of first dose of the study drug to the date of the first response of (CR, PR, or mCR).
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Timepoint [17]
0
0
Measured from Cycle 1 Day 1 as long as the participant 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 [18]
0
0
Time to First Response (ORR)
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Assessment method [18]
0
0
Time to first response (ORR) will be defined as the number of days from the date of first dose of the study drug to the date of the first response of (CR or PR).
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Timepoint [18]
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0
Measured from Cycle 1 Day 1 as long as the participant 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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Eligibility
Key inclusion criteria
- Participant must have documented diagnosis of untreated de novo MDS with:
- International Prognostic Scoring System (IPSS) risk categories Int-2 or High
(minimum IPSS overall score of 1.5) OR Revised IPSS (IPSS-R) categories
intermediate, high or very high (score of > 3) and
- Presence of less than 20% bone marrow blasts per bone marrow biopsy/aspirate.
- Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to
2.
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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
- Participant has received prior therapy for MDS. (Prior supportive care in form of
transfusions or growth factors, etc., is not considered prior therapy).
- Participant has received prior therapy with a BCL-2 Homology 3 (BH3) mimetic.
- Participant has a diagnosis other than previously untreated de novo MDS (as defined in
the protocol) including:
- MDS with IPSS risk categories Low or Int-1 (overall IPSS score < 1.5)
- Therapy-related MDS (t-MDS).
- MDS evolving from a pre-existing myeloproliferative neoplasm (MPN).
- MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic
myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and
unclassifiable MDS/MPN.
- Participant has received allogeneic Hematopoietic Stem Cell Transplantation (HSCT) or
solid organ transplantation.
- Participant has received a live attenuated vaccine within 4 weeks prior to the first
dose of study drug.
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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
Active, not recruiting
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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
12/01/2017
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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
28/06/2024
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Actual
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Sample size
Target
129
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
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Recruitment hospital [1]
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Concord Repatriation General Hospital /ID# 154958 - Concord
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Recruitment hospital [2]
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Duplicate_St. Vincent's Hospital, Darlinghurst /ID# 222846 - Darlinghurst
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Recruitment hospital [3]
0
0
St George Hospital /ID# 154954 - Kogarah
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Recruitment hospital [4]
0
0
Liverpool Hospital /ID# 222410 - Liverpool
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Recruitment hospital [5]
0
0
Calvary Mater Newcastle /ID# 154957 - Waratah
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Recruitment hospital [6]
0
0
Princess Alexandra Hospital /ID# 154990 - Woolloongabba
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Recruitment hospital [7]
0
0
Austin Health /ID# 154955 - Heidelberg
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Recruitment hospital [8]
0
0
Alfred Health /ID# 154956 - Melbourne
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Recruitment hospital [9]
0
0
Fiona Stanley Hospital /ID# 222847 - Murdoch
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Recruitment postcode(s) [1]
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0
2139 - Concord
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Recruitment postcode(s) [2]
0
0
2010 - Darlinghurst
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Recruitment postcode(s) [3]
0
0
2217 - Kogarah
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Recruitment postcode(s) [4]
0
0
2170 - Liverpool
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Recruitment postcode(s) [5]
0
0
2298 - Waratah
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Recruitment postcode(s) [6]
0
0
4102 - Woolloongabba
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Recruitment postcode(s) [7]
0
0
3084 - Heidelberg
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Recruitment postcode(s) [8]
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0
3004 - Melbourne
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Recruitment postcode(s) [9]
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0
6150 - Murdoch
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Recruitment outside Australia
Country [1]
0
0
United States of America
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State/province [1]
0
0
Arizona
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Country [2]
0
0
United States of America
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State/province [2]
0
0
Illinois
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Country [3]
0
0
United States of America
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State/province [3]
0
0
Maryland
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Country [4]
0
0
United States of America
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State/province [4]
0
0
Massachusetts
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Country [5]
0
0
United States of America
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State/province [5]
0
0
Missouri
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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]
0
0
Pennsylvania
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Country [9]
0
0
United States of America
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State/province [9]
0
0
Tennessee
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Country [10]
0
0
United States of America
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State/province [10]
0
0
Texas
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Country [11]
0
0
Canada
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State/province [11]
0
0
Ontario
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Country [12]
0
0
France
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State/province [12]
0
0
Pays-de-la-Loire
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Country [13]
0
0
France
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State/province [13]
0
0
Paris
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Country [14]
0
0
Germany
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State/province [14]
0
0
Baden-Wuerttemberg
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Country [15]
0
0
Germany
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State/province [15]
0
0
Nordrhein-Westfalen
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Country [16]
0
0
Germany
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State/province [16]
0
0
Sachsen
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Country [17]
0
0
Germany
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State/province [17]
0
0
Halle (Saale)
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Country [18]
0
0
Germany
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State/province [18]
0
0
Munich
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Country [19]
0
0
Italy
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State/province [19]
0
0
Lazio
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Country [20]
0
0
Italy
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State/province [20]
0
0
Bologna
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Country [21]
0
0
United Kingdom
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State/province [21]
0
0
Norfolk
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Country [22]
0
0
United Kingdom
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State/province [22]
0
0
Oxfordshire
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Country [23]
0
0
United Kingdom
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State/province [23]
0
0
Birmingham
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Country [24]
0
0
United Kingdom
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State/province [24]
0
0
London
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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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0
Commercial sector/Industry
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Name [1]
0
0
Genentech, Inc.
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Address [1]
0
0
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Country [1]
0
0
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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, dose-finding study evaluating
venetoclax in combination with azacitidine in participants with treatment-naïve higher-risk
MDS comprising a dose-escalation portion and a safety expansion portion.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02942290
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
0
0
ABBVIE INC.
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Address
0
0
AbbVie
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for public queries
Name
0
0
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Address
0
0
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02942290
Download to PDF