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

Acute Myeloid Leukemia

This phase Ib trial is to find out the side effects and possible benefits of decitabine alone or given together with venetoclax, gilteritinib, enasidenib, or ivosidenib in treating patients with acute myeloid leukemia that is under control (remission). Chemotherapy drugs, such as decitabine, 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. Venetoclax may stop the growth of cancer cells by blocking a protein called Bcl-2 needed for cell growth. Gilteritinib, enasidenib, and ivosidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving decitabine alone or together with venetoclax, gilteritinib, enasidenib, or ivosidenib may help to control the disease.

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.

United States