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

NCT02942290 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: M15-5312016-001657-412023-507154-32-00
• Study Type: interventional
• Target: 129
• Locations: 7 countries
• Sites: 37

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.

Conditions

Myelodysplastic Syndromes (MDS)

Keywords

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

Outcome Measures

Primary Outcomes (12)

• AUCt for Azacitidine

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

  Up to 32 days

• Cmax of venetoclax

  Maximum plasma concentration (Cmax) of venetoclax.

  Up to 32 days

• AUCt for venetoclax

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

  Up to 32 days

• Tmax of venetoclax

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

  Up to 32 days

• AUC[0 to infinity] for azacitidine

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

  Up to 32 days

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

  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 \[upon completion of the dose escalation phase\].

  Measured from Day 1 until Day 28 per dose level.

• Half-life (t[1/2]) for azacitidine

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

  Up to 32 days

• Cmax for azacitidine

  Maximum plasma concentration (Cmax) of azacitidine.

  Up to 32 days

• AUC[0-24] for venetoclax

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

  Up to 32 days

• Clearance (CL) for azacitidine

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

  Up to 32 days

• Tmax for azacitidine

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

  Up to 32 days

• Complete Remission (CR) Rate

  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).

  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.

Secondary Outcomes (18)

• Rate of red blood cell (RBC) transfusion independence

  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.

• Progression-Free Survival (PFS)

  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.

• Overall Survival (OS)

  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.

• Hematologic Improvement (HI) rate

  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.

• Rate of platelet (PLT) transfusion independence

  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.

Study Arms (1)

Venetoclax + Azacitidine

EXPERIMENTAL

Drug: Azacitidine; Drug: Venetoclax

Interventions

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 + Azacitidine

Venetoclax DRUG

Oral; Tablet

Also known as: ABT-199, GDC-0199, VENCLEXTA

Venetoclax + Azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead
• Genentech, Inc.: collaborator

Study Sites (37)

Duplicate_University of Arizona Cancer Center - North Campus /ID# 154155

Tucson, Arizona, 85719-1478, United States

Location

The University of Chicago Medical Center /ID# 153673

Chicago, Illinois, 60637-1443, United States

Location

University of Maryland, Baltimore /ID# 153669

Baltimore, Maryland, 21201, United States

Location

Tufts Medical Center /ID# 153672

Boston, Massachusetts, 02111-1552, United States

Location

Dana-Farber Cancer Institute /ID# 152735

Boston, Massachusetts, 02215, United States

Location

Washington University-School of Medicine /ID# 153671

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center /ID# 153661

New York, New York, 10032-3729, United States

Location

Weill Cornell Medical College /ID# 155524

New York, New York, 10065, United States

Location

Oregon Medical Research Center /ID# 152734

Portland, Oregon, 97239, United States

Location

University of Pittsburgh MC /ID# 153662

Pittsburgh, Pennsylvania, 15260, United States

Location

Tennessee Oncology-Nashville Centennial /ID# 222769

Nashville, Tennessee, 37203-1632, United States

Location

Vanderbilt University Medical Center /ID# 152738

Nashville, Tennessee, 37232-0011, United States

Location

UT MD Anderson Cancer Center /ID# 153809

Houston, Texas, 77030, United States

Location

Concord Repatriation General Hospital /ID# 154958

Concord, New South Wales, 2139, Australia

Location

Duplicate_St. Vincent's Hospital, Darlinghurst /ID# 222846

Darlinghurst, New South Wales, 2010, Australia

Location

St George Hospital /ID# 154954

Kogarah, New South Wales, 2217, Australia

Location

Liverpool Hospital /ID# 222410

Liverpool, New South Wales, 2170, Australia

Location

Calvary Mater Newcastle /ID# 154957

Waratah, New South Wales, 2298, Australia

Location

Duplicate_Princess Alexandra Hospital /ID# 154990

Woolloongabba, Queensland, 4102, Australia

Location

Austin Health /ID# 154955

Heidelberg, Victoria, 3084, Australia

Location

The Alfred Hospital /ID# 154956

Melbourne, Victoria, 3004, Australia

Location

Fiona Stanley Hospital /ID# 222847

Murdoch, Western Australia, 6150, Australia

Location

Juravinski Cancer Centre /ID# 152947

Hamilton, Ontario, L8V 1C3, Canada

Location

Centre Hospitalier Universitaire de Nantes, Hotel Dieu -HME /ID# 153828

Nantes, Pays de la Loire Region, 44000, France

Location

Hôpital Saint-Louis /ID# 153827

Paris, 75010, France

Location

Universitatsklinikum Mannheim /ID# 153140

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Klinikum rechts der Isar /ID# 153139

Munich, Bavaria, 81675, Germany

Location

Universitaetsklinikum Koeln /ID# 153141

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Duplicate_Universitaetsklinikum Carl Gus /ID# 153958

Dresden, Saxony, 01307, Germany

Location

Universitaetsklinikum Leipzig /ID# 153142

Leipzig, Saxony, 04103, Germany

Location

Universitaetsklinikum Halle (Saale) /ID# 153760

Halle, 06120, Germany

Location

Duplicate_IRCCS AOU di Bologna - Policlinico Sant'Orsola-Malpighi /ID# 153763

Bologna, Emilia-Romagna, 40138, Italy

Location

Duplicate_Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 153764

Rome, Roma, 00161, Italy

Location

Norfolk and Norwich University Hospitals NHS Foundation Trust /ID# 156492

Norwich, Norfolk, NR4 7UY, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust /ID# 222567

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust /ID# 158810

Birmingham, B15 2TH, United Kingdom

Location

King's College Hospital NHS Foundation Trust /ID# 156489

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• Garcia JS, Platzbecker U, Odenike O, Fleming S, Fong CY, Borate U, Jacoby MA, Nowak D, Baer MR, Peterlin P, Chyla B, Wang H, Ku G, Hoffman D, Potluri J, Garcia-Manero G. Efficacy and safety of venetoclax plus azacitidine for patients with treatment-naive high-risk myelodysplastic syndromes. Blood. 2025 Mar 13;145(11):1126-1135. doi: 10.1182/blood.2024025464.

  PMID: 39652823 DERIVED

Related Links

• This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2016
• First Posted: October 24, 2016
• Study Start: January 12, 2017
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: August 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (9); IT (2); DE (6); GB (4); FR (2); US (13); CA (1)