Venetoclax and Azacitidine for the Treatment of Acute Myeloid Leukemia in the Post-Transplant Setting

NCT04128501 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2019-0353NCI-2019-06674
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well venetoclax and azacitidine work for the treatment of acute myeloid leukemia after stem cell transplantation. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax and azacitidine after a stem cell transplant may help control high risk leukemia and prevent it from coming back after the transplant.

Conditions

Acute Bilineal Leukemia; Acute Biphenotypic Leukemia; Acute Myeloid Leukemia; Mixed Phenotype Acute Leukemia; T Acute Lymphoblastic Leukemia; Therapy-Related Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Relapse-free survival (RFS) time

  Summary statistics for RFS time will be computed for all patients and within each (disease status, disease type) subgroup. RFS time distributions will be estimated within each subgroup using the method of Kaplan and Meier.

  From the date of first administration of venetoclax + azacitidine (vidaza) (V+V), assessed up to 60 days after last V+V dose

Secondary Outcomes (5)

• Overall survival (OS) time

  Up to 60 days after last V+V dose

• Incidence of severe (grade 3 or 4) infection

  Up to 60 days after last V+V dose

• Graft-versus-host disease

  Up to 60 days after last V+V dose

• Incidence of other inter-current adverse events during follow up

  Up to 60 days after last V+V dose

• Non-relapse mortality

  Within 90 days from the start of V+V treatment

Study Arms (1)

Treatment (azacitidine, venetoclax)

EXPERIMENTAL

Patients receiving venetoclax and azacitidine for maintenance after allogeneic stem cell transplantation, receive azacitidine SC on days 1-5 and venetoclax PO QD on days 1-7. Patients receiving venetoclax and azacitidine for minimal residual disease after allogeneic stem cell transplant, receive azacitidine SC on days 1-5 and venetoclax PO QD on days 1-14. Treatment repeats every 4-8 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Drug: Venetoclax

Interventions

Azacitidine DRUG

Given SC

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, Onureg, U-18496, Vidaza

Treatment (azacitidine, venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (azacitidine, venetoclax)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants 18 to 75 years of age.
• English and non-English speaking patients are eligible.
• Disease diagnosis with one of the hematological malignancies listed below and who are in morphological remission after allogeneic stem cell transplantation with PBSCs or bone marrow.
• AML if they had at least one of the following disease characteristics:
• Therapy related AML.
• Cytogenetics and molecular features consistent with adverse risk group by European LeukemiaNet classification for AML (see Appendix A.).
• Primary induction failure defined as absence of complete remission after two different lines of anti-leukemia therapy following diagnosis.
• Presence of minimal residual disease by multi-color flow cytometry or cytogenetics or molecular studies at the time of HSCT.
• Presence of active disease defined as bone marrow blast count \>5% at the time of HSCT.
• Participants transplanted beyond first remission. OR
• Biphenotypic or bilineage leukemia (including a myeloid component) OR mixed phenotype acute leukemia (MPAL) OR
• Participants with acute lymphoblastic leukemia; B cell or T cell in original.
• Participants in morphological remission with no detectable minimal residual disase (MRD) after transplant
• Participants who are in remission with no detectable minimal residual disease (MRD) after allogeneic stem cell transplant should have:
• Adequate engraftment within 14 days prior to starting study drug:

You may not qualify if:

• Active acute GVHD grade II or higher.
• Active chronic GVHD that is extensive (see Appendix C.).
• Uncontrolled GVHD (see Appendix C.).
• Concurrent use of systemic immune suppressive other than calcineurin inhibitors, sirolimus and steroids
• Active uncontrolled systemic fungal, bacterial or viral infection.
• Active bleeding.
• Symptomatic or uncontrolled arrhythmias.
• Significant active cardiac disease within the previous 6 months, including:
• New York Heart Association (NYHA) class III or IV congestive heart failure see Appendix C.).
• Unstable angina or angina requiring surgical or medical intervention, and/or b. Myocardial infarction.
• Known active viral infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
• Prior history of malignancies, other than leukemia, unless the subject has been free of the disease for \>/= 1 year. However, participants with the following history/concurrent conditions are allowed:
• Basal or squamous cell carcinoma of the skin;
• Carcinoma in situ of the cervix;
• Carcinoma in situ of the breast;

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Leukemia, Myeloid, Acute; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Precursor Cell Lymphoblastic Leukemia-Lymphoma

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

• Betul Oran

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: October 16, 2019
• Study Start: May 5, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

US (1)