AZA + Venetoclax as Maintenance Therapy in Patients With AML in Remission

NCT04062266 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2019-0226NCI-2019-04987
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well azacitidine and venetoclax work in treating patients with acute myeloid leukemia that is in remission. Drugs used in chemotherapy, such as azacitidine and venetoclax, 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.

Conditions

FLT3 Gene Mutation; Acute Myeloid Leukemia; Minimal Residual Disease Persistence; Therapy-Related Acute Myeloid Leukemia; Acute Myeloid Leukemia in Remission; Hematologic and Lymphocytic Disorder

Outcome Measures

Primary Outcomes (1)

• Relapse-free survival (RFS)

  The study will be continuously monitored for the primary endpoint, RFS, using the method of Thall, Wooten, and Tannir (2005). Will also summarize the posterior distribution of lambda-E (i.e., median RFS) assuming posterior mean and 95% credible interval.

  From date of complete remission (CR) or complete remission with incomplete count recovery (CRi), assessed for up to 10 years

Secondary Outcomes (5)

• Incidence of toxicity

  Up to 10 years

• Modified RFS

  Time from enrollment on study until date of first objective documentation of relapse or death, assessed for up to 10 years

• Overall survival (OS)

  From the start of study treatment until date of death due to any cause, assessed for up to 10 years

• Event free survival (EFS)

  From the start of study treatment until date of first confirmed relapse, withdrawal from study due to adverse event, or death due to any cause, assessed for up to 10 years

• Complete remission duration (CRd)

  Time from CR or CRi until date of first objective documentation of confirmed relapse, assessed for up to 10 years

Study Arms (1)

Treatment (azacytidine, venetoclax)

EXPERIMENTAL

Patients receive azacitidine SC or IV over 1 hour daily on days 1-5, and venetoclax PO daily on days 1-14. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Drug: Venetoclax

Interventions

Venetoclax DRUG

Given PO

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

Treatment (azacytidine, venetoclax)

Azacitidine DRUG

Given SC or IV

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

Treatment (azacytidine, venetoclax)

Eligibility Criteria

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

You may qualify if:

• Patients aged \>/= 18 years AML who have achieved their FIRST CR or CRi and are not immediately candidates for allogeneic stem cell transplant.
• Patients who have received intensive therapy (defined as receiving standard or higher dose cytarabine-based therapy) to achieve remission (CR/CRi) should have received remission induction therapy and at least 1 consolidation cycle. These patients are eligible as long as they are not greater than 2 months from their last consolidation therapy and will be enrolled in COHORT 1.
• Patients who have received lower intensity therapy (defined as receiving low-dose cytarabine (LDAC) or hypomethylating agent (HMA)-based therapy) to achieve remission should have received at least 2 cycles of lower intensity therapy between the time they have achieved CR/CRi and enrollment on this protocol. They will be treated on COHORT 2.
• For either subgroup (lower or higher intensity), patients who have measurable residual disease may be enrolled on their respective cohort at any time without maximum 'time from consolidation' requirement.
• ECOG performance status of \< or = 3
• Adequate organ function as follows:
• Serum total bilirubin \< or = to 1.5 X the Upper Limit of Normal (ULN)
• Serum creatinine \< or = to 2.5 x ULN
• Adequate BM reserve:
• Absolute neutrophil count (ANC) \> 0.5 x k/uL
• Platelet count \> or = 30 x k/uL
• For females of childbearing age, they may participate if they:
• Have a negative serum or urine pregnancy test within 10 to 14 days of enrolling
• Agree to either abstinence or 2 effective contraceptive methods (such as barrier methods or hormonal contraception) throughout the treatment period and up to 30 days after discontinuing treatment.
• For male patients with a female partner of childbearing age, they may participate if they agree to either abstinence or 2 effective contraceptive methods throughout the treatment period and up to 30 days after discontinuing treatment.

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia (APL), AML - M3 by FAB classification based on morphology, immunophenotype, molecular, or cytogenetic s studies.
• Diagnosis of AML associated t(15;17) or APL variant. Patients with t(9;22) are also ineligible unless they are unable or unwilling to receive therapy with a tyrosine kinase inhibitor.
• Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with active CNS (central nervous system) disease.
• Patients with documented hypersensitivity to any components of the study program.
• Females who are pregnant or lactating or intending to become pregnant during the study.
• Patients with history of extramedullary AML, except for CNS involvement that is currently controlled, will not be eligible for enrollment.
• Patient should be removed from current trial if they wish to participate and get treatment on another trial.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Bazinet A, Kantarjian H, Bataller A, Pemmaraju N, Borthakur G, Chien K, Alvarado Y, Bose P, Jabbour E, Yilmaz M, DiNardo C, Issa G, Montalban-Bravo G, Short N, Sasaki K, Bull-Linderman D, Daver N, Garcia-Manero G, Ravandi F, Kadia T. Reduced dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia following intensive or low-intensity induction: a single-centre, single-arm, phase 2 trial. Lancet Haematol. 2024 Apr;11(4):e287-e298. doi: 10.1016/S2352-3026(24)00034-6.

  PMID: 38548404 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Hematologic Diseases; Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

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

• Tapan M Kadia

  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: August 16, 2019
• First Posted: August 20, 2019
• Study Start: September 13, 2019
• Primary Completion (Estimated): October 31, 2030
• Study Completion (Estimated): October 31, 2030
• Last Updated: January 13, 2026

Record last verified: 2026-01

Locations

US (1)