Azacitidine and Venetoclax as Induction Therapy With Venetoclax Maintenance in the Elderly With AML

NCT03466294 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-7821.cc
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to determine if treatment with azacitidine and venetoclax is effective treatment for elderly patients with acute myeloid leukemia (AML) who have not received previous treatment. Azacitidine and venetoclax will be given as induction treatment followed by venetoclax maintenance treatment for patients who respond to the induction treatment.

Conditions

Acute Myeloid Leukemia

Keywords

Azacitidine; Venetoclax; AML

Outcome Measures

Primary Outcomes (1)

• Duration of Remission Response to Azacitidine and Venetoclax Treatment + Maintenance Therapy

  To determine the remission duration experienced by elderly previously untreated AML patients with azacitidine plus venetoclax followed by venetoclax alone as a maintenance therapy for patients who achieve a minimal residual disease (MRD) negative remission

  From the first day a response is documented to the first day of disease progression

Secondary Outcomes (3)

• Response Rate, With Responses Defined as Complete Remission (CR), Complete Remission With Incomplete Blood Count Recovery (CRi) and Morphologic Leukemia Free State (MLFS).

  From Day 28, the first day a response is documented to end of cycle bone marrow biopsies, through 5 years

• MRD-Negativity Incidence

  From Day 28, the first day a response is documented to end of cycle bone marrow biopsies, through 5 years

• To Determine the Median Time to Achieve a MRD Negative Composite Response

  From first dose of treatment to first day response is documented by bone marrow biopsy, on average 30 days

Study Arms (1)

Azacitidine and Venetoclax

EXPERIMENTAL

On day 1 of cycle 1, Azacitidine 75 mg/m2 will be given by injection or infusion, and will continue for 7 days. Azacitidine doses will be given in subsequent cycles for patients who do not achieve response. Venetoclax will be administered orally once daily on days 2 through 28 in cycle 1. Beginning with cycle 2, and each subsequent cycle, venetoclax will be administered Days 1 through 28.

Drug: Azacitidine and Venetoclax

Interventions

Azacitidine and Venetoclax DRUG

Azacitidine will be given at dose of 75mg/m2 in Cycle 1 days 1-7; repeat in cycle 2 and 3 if no response. Starting on day 2 of cycle 1, venetoclax will be administered orally with doses increased to a target dose of 600 mg (administer 100 mg on day 2, 200 mg on day 3, 400 mg on day 4 and 600 mg on day 5), then 600 mg daily.

Azacitidine and Venetoclax

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must have confirmation of non-APL AML by WHO criteria and be ineligible or unwilling to undergo treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidities or other factors
• Subject must have received no prior treatment for AML; hydroxyurea is not considered a treatment and is allowed
• Subject must be ≥ 60 years of age
• Subject must have a projected life expectancy of at least 12 weeks
• Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of ≤2
• Subject must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula
• Subject must have adequate liver function as demonstrated by:
• aspartate aminotransferase (AST) ≤ 3.0 × ULN\*
• alanine aminotransferase (ALT) ≤ 3.0 × ULN\*
• bilirubin ≤ 3.0 × ULN, unless due to Gilbert's syndrome\*
• Unless considered due to leukemic organ involvement
• Non-sterile male subjects must use contraceptive methods with partner(s) prior to beginning study drug administration and continuing up to 90 days after the last dose of study drug. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug.
• Female subjects must be either:
• Postmenopausal; defined as Age \> 55 years with no menses for 12 or more months without an alternative medical cause; OR
• Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)

You may not qualify if:

• Subject has received treatment with a hypomethylating agent and/or other chemotherapeutic agent either conventional or experimental for myelodysplastic syndrome (MDS) or AML
• Subject has acute promyelocytic leukemia
• Subject has known active CNS involvement from AML
• Subject is known to be positive for HIV. HIV testing is not required
• Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load. Hepatitis B or C testing is not required and subjects with serologic evidence of prior vaccination to HBV (i.e., HBs Ag, anti-HBs+ and anti-HBc-) may participate
• Subject has received anticancer therapies including chemotherapy, radiotherapy or other investigational therapy, including targeted small molecule agents within 5 half-lives prior to first dose of study drug
• Subject has received biologic agents (e.g. monoclonal antibodies) for anti-neoplastic intent within 30 days prior to first dose of study drug
• Subject has received the following within 7 days prior to the first dose of the study drug:
• Steroid therapy for anti-neoplastic intent;
• Strong and Moderate CYP3A inhibitors (see Appendix A for examples)
• Strong and Moderate CYP3A inducers (see Appendix A for examples)
• Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment
• Subject has any history of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study including, but not limited to:
• New York Heart Association heart failure \> class 2
• Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Shallis RM, Podoltsev NA. Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Curr Opin Hematol. 2021 Mar 1;28(2):110-121. doi: 10.1097/MOH.0000000000000637.

  PMID: 33394722 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Single-arm design without a comparator limits causal inference. Outcomes are based on a relatively small, older AML cohort at a single center and may not generalize broadly. Duration estimates are subject to censoring; missing data were not imputed.

Results Point of Contact

• Title: Dr. Daniel Pollyea
• Organization: University of Colorado

DANIEL.POLLYEA@CUANSCHUTZ.EDU

3037249562

Study Officials

• Dan Pollyea

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: March 2, 2018
• First Posted: March 15, 2018
• Study Start: May 15, 2018
• Primary Completion: January 29, 2025
• Study Completion: December 4, 2025
• Last Updated: April 9, 2026
• Results First Posted: April 7, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)