Decitabine Alone or in Combination With Venetoclax, Gilteritinib, Enasidenib, or Ivosidenib as Maintenance Therapy for the Treatment of Acute Myeloid Leukemia in Remission

PRIMARY OBJECTIVE:

I. To assess safety of patients with acute myeloid leukemia (AML) treated with decitabine and cedazuridine (oral decitabine)-based combinations as maintenance therapy after achieving remission.

SECONDARY OBJECTIVES:

I. To assess relapse-frees survival (RFS) of patients with AML treated with oral decitabine-based combinations as maintenance therapy.

II. To assess overall survival (OS) of patients with AML treated with oral decitabine-based combinations as maintenance therapy.

III. To assess event-free survival (EFS) of patients with AML treated with oral decitabine-based combinations as maintenance therapy.

IV. To assess the duration of remission (CRd) of patients with AML treated oral decitabine-based combinations as maintenance therapy.

V. To assess the effects of oral decitabine-based combinations on dynamics of minimal residual disease and their relationship to outcomes.

EXPLORATORY OBJECTIVE:

I. To evaluate RFS in (1) intensive induction cohort and (2) lower intensity induction cohort.

OUTLINE: Patients are assigned to 1 of 5 arms.

ARM A: Patients receive decitabine and cedazuridine orally (PO) once daily (QD) on days 1-3. Treatments repeat every 28 days for up to 4 weeks in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive decitabine and cedazuridine PO QD on days 1-3 and venetoclax PO QD on days 1-5. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive decitabine and cedazuridine PO QD on days 1-3 and gilteritinib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

ARM D: Patients receive decitabine and cedazuridine PO QD on days 1-3 and enasidenib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

ARM E: Patients receive decitabine and cedazuridine PO QD on days 1-3 and ivosidenib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6-12 months.

Inclusion criteria

• Patients aged >= 18 years AML who have achieved their FIRST complete response (CR) or complete response with incomplete bone marrow recovery (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 designated as COHORT 1 (intensive induction cohort)
• 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 designated as COHORT 2 (lower intensity induction cohort)
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status of < or = 3
• Serum total bilirubin < or = to 1.5 x the upper limit of normal (ULN)
• Serum creatinine < or = to 2.5 x ULN
• Absolute neutrophil count (ANC) > 0.5 x k/uL
• Platelet count > or = 50 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
• Ability to understand and sign informed consent

Exclusion criteria

• Diagnosis of acute promyelocytic leukemia (APL), AML - M3 by French-American-British (FAB) classification based on morphology, immunophenotype, molecular, or cytogenetics 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