Spots Global Cancer Trial Database for Decitabine/Cedazuridine and Venetoclax in Combination With Ivosidenib or Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Study Description

Brief Summary: This phase Ib/II trials studies the side effects of decitabine/cedazuridine (ASTX727) and venetoclax in combination with ivosidenib or enasidenib, and how well they work in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). ASTX727 is the combination of a fixed dose of 2 drugs, cedazuridine and decitabine. Cedazuridine may slow down how fast decitabine is broken down by the body, and decitabine may block abnormal cells or cancer cells from growing. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Enasidenib and ivosidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving decitabine/cedazuridine and venetoclax in combination with ivosidenib or enasidenib may help control acute myeloid leukemia.

Detailed Description: PRIMARY OBJECTIVE: I. To determine the safety and tolerability and recommended phase 2 dose (RP2D) of oral decitabine/cedazuridine (ASTX727) and venetoclax in combination with either ivosidenib (Arm A) or enasidenib (Arm B) for patients with acute myeloid leukemia. (Phase Ib) II. To determine the overall response rate (complete response \[CR\], complete remission with incomplete hematologic recovery \[CRh\], morphologic leukemia-free state \[MLFS\] and partial response \[PR)\] of oral decitabine/cedazuridine (ASTX727) and venetoclax in combination with either ivosidenib (Arm A) or enasidenib (Arm B) for patients with acute myeloid leukemia. (Phase 2) SECONDARY OBJECTIVES: I. To determine duration of response (DOR), event-free survival (EFS), and overall survival (OS). II. To evaluate occurrence of minimal residual disease (MRD) negative status by multiparameter flow cytometry and molecular evaluation. EXPLORATORY OBJECTIVE: I. To investigate global gene expression profiles, deoxyribonucleic acid (DNA) methylation profiles, BH3 profiling and other potential prognostic markers to explore predictors of antitumor activity and/or resistance to treatment. OUTLINE: Patients are assigned to 1 of 2 arms. ARM A: Patients receive decitabine/cedazuridine orally (PO) daily on days 1-5, venetoclax PO daily on days 1-14, and ivosidenib PO daily on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive decitabine/cedazuridine PO daily on days 1-5, venetoclax PO daily on days 1-14, and enasidenib PO daily on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

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