Clinical Trials /

A Study Evaluating Venetoclax in Combination With Azacitidine in Participants With Treatment-Naïve Higher-Risk Myelodysplastic Syndromes (MDS)

NCT02942290

Description:

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.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating Venetoclax in Combination With Azacitidine in Participants With Treatment-Naïve Higher-Risk Myelodysplastic Syndromes (MDS)
  • Official 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)

Clinical Trial IDs

  • ORG STUDY ID: M15-531
  • SECONDARY ID: 2016-001657-41
  • NCT ID: NCT02942290

Conditions

  • Myelodysplastic Syndromes (MDS)

Interventions

DrugSynonymsArms
AzacitidineVenetoclax + Azacitidine
VenetoclaxABT-199, GDC-0199, VENCLEXTAVenetoclax + Azacitidine

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Venetoclax + AzacitidineExperimental
  • Azacitidine
  • Venetoclax

Eligibility Criteria

        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.

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:AUCt for azacitidine
Time Frame:Up to 32 days
Safety Issue:
Description:Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for azacitidine.

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame: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.
Safety Issue:
Description: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 from any cause.
Measure:Rate of red blood cell (RBC) transfusion independence
Time Frame: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.
Safety Issue:
Description:Percentages of participants who become RBC transfusion-independent.
Measure:Progression-Free Survival (PFS)
Time Frame: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.
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame: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.
Safety Issue:
Description: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.
Measure:Hematologic Improvement (HI) rate
Time Frame: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.
Safety Issue:
Description:Percentages of participants with HI (erythroid/platelet/neutrophil responses).
Measure:Rate of platelet (PLT) transfusion independence
Time Frame: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.
Safety Issue:
Description:Percentages of participants who become platelet transfusion-independent.
Measure:Event-Free Survival (EFS)
Time Frame: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 subject is enrolled
Safety Issue:
Description: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.
Measure:Time to transformation to acute myeloid leukemia (AML)
Time Frame: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.
Safety Issue:
Description:Defined as the number of days from the date of the first dose of study drug to the date of documented AML transformation.
Measure:Complete Remission (CR) rate
Time Frame: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.
Safety Issue:
Description:Complete remission rate will be defined as the proportion of subjects who achieved a complete response per the International Working Group (IWG) 2006 criteria for Myelodysplastic Syndromes (MDS).
Measure:Overall Response Rate (ORR)
Time Frame: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.
Safety Issue:
Description:ORR (equals the rates of complete remission [CR] + marrow complete remission [mCR] + partial remission [PR]) of venetoclax in combination with azacitidine.
Measure:Time to next treatment (TTNT)
Time Frame: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 subject is enrolled.
Safety Issue:
Description: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.
Measure:Marrow Complete Remission (mCR) Rate
Time Frame: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.
Safety Issue:
Description:Defined as the proportion of subjects who achieved a marrow complete response with or without hematological improvement per the International Working Group (IWG) 2006 criteria for Myelodysplastic Syndromes.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Higher-Risk (HR) Myelodysplastic Syndromes (MDS)
  • Pharmacokinetic
  • Venetoclax
  • Azacitidine
  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndromes (MDS)
  • Treatment-Naïve Higher-Risk

Last Updated

June 22, 2020