Discontinuation of Hypomethylating Agent and Venetoclax for the Treatment of Newly Diagnosed Acute Myeloid Leukemia in Patients Who Have Achieved Negative Measurable Residual Disease

PRIMARY OBJECTIVE:

I. To determine complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) at 18 months from the time of initial CR/CRi in patients who discontinue frontline HMA (azacitidine or decitabine)/venetoclax (VEN) after achieving MRD negativity by multiparameter flow cytometry (MFC) within 12 months of starting therapy.

SECONDARY OBJECTIVES:

I. To assess overall survival (OS) in MRD-negative patients who discontinue HMA (azacitidine or decitabine)/VEN.

II. To assess MRD-negative CR/CRi and CR/CRi and rates to re-treatment following molecular or morphologic relapse duration discontinuation.

III. To assess duration of treatment free molecular remission (TFMR) defined as time from MRD negativity to first MRD positivity.

IV. To assess changes in quality of life (QoL) and symptoms by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) Global Health Status (GHS)/QoL, Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue, and European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L) Visual Analog Scale (VAS).

EXPLORATORY OBJECTIVES:

I. To describe new clones that emerges following molecular or morphologic relapse.

II. To describe if there is a difference on outcomes in patients who achieved MRD negativity by MFC with detection level ≤ 0.1% (3-log deep) versus ≤ 0.01% (4-log deep).

III. To correlate outcomes and targeted gene MRD status when applicable.

OUTLINE: Patients with < 12 months of standard of care (SOC) HMA therapy proceed to Consolidation Phase. Patients with 12 months of SOC HMA therapy proceed to the Discontinuation Phase.

CONSOLIDATION PHASE: Patients receive standard of care (SOC) HMA consisting of azacitidine intravenously (IV) or decitabine plus venetoclax in the absence of disease progression, unacceptable toxicity, or MRD positivity until 12 months of total therapy. Patients who remain MRD negative then proceed to the discontinuation phase.

DISCONTINUATION PHASE: Patients undergo bone marrow biopsies every 3 months for up to 24 months on study. Patients who experience a molecular relapse (including MRD positivity) receive HMA as in Consolidation Phase with bone marrow biopsies every 3 months for up to 24 months total in the absence of disease progression, unacceptable toxicity, or MRD positivity. Patients who experience a morphologic relapse receive HMA consisting of azacitidine IV or decitabine plus venetoclax. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

Patients also undergo bone marrow biopsy during screening, during the Consolidation Phase, and follow-up.

After completion of study intervention, patients are followed every 6 months for up to 2 years.