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RecruitingInterventionalPhase 2

Discontinuation of Hypomethylating Agent and Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) Who Have Achieved Negative Measurable Residual Disease (MRD)

NCT ID: NCT06511882Sponsor: H. Lee Moffitt Cancer Center and Research InstituteLast updated: 2026-02-27

Summary

The purpose of this research study is to see if people whose Acute myeloid leukemia (AML) is being successfully treated with azacitidine or decitabine in combination with venetoclax can discontinue this chemotherapy for some period of time after a year of treatment without increasing the likelihood that their AML will return.

Arms & interventions

  • DrugAzacitidine

    Standard of Care Intravenous (IV) infusion

  • DrugDecitabine

    Standard of Care Intravenous (IV) infusion

  • DrugVenetoclax

    Standard of Care PO (By Mouth)

Outcome measures

Primary

  • Rates of Complete Response (CR)/Complete Response with incomplete hematologic recovery (CRi)

    Rates of CR/CRi at 18 months from the time of initial CR/CRi in patients who discontinue frontline HMA (azacitidine or decitabine)/VEN (venetoclax) after achieving Measurable Residual Disease (MRD) negativity by MFC within 12 months of starting therapy. The Null hypothesis (p0) will be tested against the alternative hypothesis (p1). Null hypothesis: p0 ≤ 50% will remain in CR/CRi at 18 months from the time of initial CR/CRi Alternative hypothesis: p1 ≥ 70% will remain in CR/CRi at 18 months from the time of initial CR/CRi

    Time frame: Up to 18 Months

Secondary

  • Overall Survival (OS)

    Time frame: Up to 36 Months

  • Rates to Re-Treatment

    Time frame: Up to 36 Months

  • Treatment Free Molecular Remission (TFMR)

    Time frame: Up to 36 Months

  • European Organization for Research and Treatment of Cancer (EORTC-QLQ-C30)/Quality of Life (QoL)

    Time frame: Day 1 (start of enrollment), start of Discontinuation Phase, and monthly until EOT (Up to 36 Months)

  • Patient Reported Outcome Measurement Information System (PROMIS)

    Time frame: Day 1 (start of enrollment), start of Discontinuation Phase, and monthly until EOT (Up to 36 Months)

  • EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)

    Time frame: Day 1 (start of enrollment), start of Discontinuation Phase, and monthly until EOT (Up to 36 Months)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Adults 18 years of age or older at the time of obtaining informed consent. * Diagnosed with Acute Myeloid Leukemia (AML) (non-M3) as defined by 2016 World Health Organization (WHO) * Eastern Cooperative Group (ECOG) performance status score ≤ 2 * Currently on frontline therapy with HMA (azacitidine or decitabine)/VEN and achieved Complete Remission (CR)/Complete Remission with incomplete marrow recovery (CRi) with MRD negativity defined as \< 0.1% by Multiparameter Flow Cytometry (MFC) * Within 12 months of starting HMA (azacitidine or decitabine)/VEN * Ineligible for or declined allogeneic hematopoietic cell transplantation (HCT) * Ability to understand and the willingness to sign a written informed consent document * Must agree to adhere to the study visit schedule and other protocol requirements * Patients must be able to provide adequate Bone Marrow (BM) aspirate and biopsy specimens for histopathological and Measurable Residual Disease analysis during the screening procedure Exclusion Criteria: * Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of AML within 28 days, or 5 half-lives, at the start of the study. Only patients who are receiving frontline HMA (azacitidine or decitabine)/VEN are potentially eligible, but if they had received a course of hydroxyurea prior to achieving CR/CRi, this is allowed. * Any serious medical condition or uncontrolled current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or will place the subject at unacceptable risk if he/she participates in the study. Controlled infections or other medical conditions on long-term therapy is allowed. * Patients who harbored TP53 mutation at diagnosis * AML with extramedullary involvement including central nervous system (CNS) involvement, myeloid sarcoma, and leukemia cutis requiring directed therapy at the time of enrollment. * Patient is pregnant.

Study locations (1)

Moffitt Cancer Center

Tampa, Florida, 33612

Recruiting
Onyee Chan, MD · Principal Investigator
Rami Komrokji, MD · Sub Investigator
Timothy Kubal, MD · Sub Investigator
Andrew Kuykendall, MD · Sub Investigator
Jeffrey Lancet, MD · Sub Investigator
Eric Padron, MD · Sub Investigator
David Sallman, MD · Sub Investigator
Alison Walker, MD · Sub Investigator