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NCT Number: NCT02942290

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

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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This study is active but is not currently recruiting participants.

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Key information

Conditions

Myelodysplastic Syndromes (MDS) Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Concord Repatriation General Hospital /ID# 154958, Concord, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Azacitidine

Drug

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.

Venetoclax

Drug

Oral; Tablet

Other names: ABT-199, GDC-0199, VENCLEXTA

Primary outcomes

  1. AUCt for Azacitidine

    Time frame: Up to 32 days

    Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for azacitidine.

  2. Cmax of venetoclax

    Time frame: Up to 32 days

    Maximum plasma concentration (Cmax) of venetoclax.

  3. AUCt for venetoclax

    Time frame: Up to 32 days

    Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for venetoclax.

  4. Tmax of venetoclax

    Time frame: Up to 32 days

    Time to Cmax (peak time, Tmax) of venetoclax.

  5. AUC[0 to infinity] for azacitidine

    Time frame: Up to 32 days

    Area under the plasma concentration-time curve from Time 0 to infinite time.

  6. Recommended Phase 2 dose (RPTD) and dosing schedule of venetoclax in combination with azacitidine

    Time frame: Measured from Day 1 until Day 28 per dose level.

    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].

  7. Half-life (t[1/2]) for azacitidine

    Time frame: Up to 32 days

    Terminal elimination half-life (t[1/2]) for azacitidine.

  8. Cmax for azacitidine

    Time frame: Up to 32 days

    Maximum plasma concentration (Cmax) of azacitidine.

  9. AUC[0-24] for venetoclax

    Time frame: Up to 32 days

    AUC over a 24-hour dose interval (AUC[0-24]) for venetoclax.

  10. Clearance (CL) for azacitidine

    Time frame: Up to 32 days

    Clearance is defined as the volume of plasma cleared of the drug per unit time.

  11. Tmax for azacitidine

    Time frame: Up to 32 days

    Time to Cmax (peak time, Tmax) of azacitidine.

  12. Complete Remission (CR) Rate

    Time frame: 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.

    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).

Secondary outcomes

  1. Rate of red blood cell (RBC) transfusion independence

    Time frame: 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.

    Percentages of participants who become RBC transfusion-independent.

  2. 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.

    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.

  3. 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 participant is enrolled.

    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.

  4. Hematologic Improvement (HI) rate

    Time frame: 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.

    Percentages of participants with HI (erythroid/platelet/neutrophil responses).

  5. Rate of platelet (PLT) transfusion independence

    Time frame: 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.

    Percentages of participants who become platelet transfusion-independent.

  6. 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 participant is enrolled

    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.

  7. 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.

    Defined as the number of days from the date of the first dose of study drug to the date of documented AML transformation.

  8. Overall Response Rate (OR)

    Time frame: 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.

    OR (equals the rates of complete remission [CR] + partial remission [PR]) of venetoclax in combination with azacitidine.

  9. 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 participant is enrolled.

    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.

  10. Marrow Complete Remission (mCR) Rate

    Time frame: 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.

    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.

  11. Modified Overall Response Rate (mOR)

    Time frame: 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.

    mOR (equals CR + PR + mCR) of venetoclax in combination with azacitidine.

  12. Duration of CR

    Time frame: 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.

    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.

  13. Duration of mOR

    Time frame: 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.

    Duration of response (mOR) 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.

  14. Duration of OR

    Time frame: 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.

    Duration of response (OR) 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.

  15. Rate of AML transformation

    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.

    The AML transformation rate is defined as the proportion of participants transformed to Acute Myelogenous Leukemia.

  16. Time to First Response (CR)

    Time frame: 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.

    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.

  17. Time to First Response (mOR)

    Time frame: 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.

    Time to first response (mOR) 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).

  18. Time to First Response (OR)

    Time frame: 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.

    Time to first response (OR) 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).

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Collaborators

  • Genentech, Inc.

Registry information

Official study 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)

Important dates

Study start
2017
Primary completion
2027
Study completion
2027
First posted
Oct 24, 2016
Registry last updated
May 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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