A Phase II Randomized Clinical Trial of Venetoclax Combined With FLAG IDA Induction and Consolidation Compared to Standard of Care for Newly Diagnosed Patients With Acute Myeloid Leukemia
This phase II trial compares induction and consolidation therapy with fludarabine, cytarabine, idarubicin, and venetoclax to cytarabine and daunorubicin induction and cytarabine consolidation for the treatment of acute myeloid leukemia (AML). Patients with AML often receive induction and consolidation therapy. Induction therapy is given first to get the patient's AML under control (remission). Consolidation therapy is given after the cancer has disappeared following the initial therapy. Consolidation therapy is used to kill any cancer cells that may be left in the body. Chemotherapy drugs, such as fludarabine, cytarabine, idarubicin, and daunorubicin, 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 is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving fludarabine, cytarabine, idarubicin, and venetoclax for induction and consolidation therapy may be more effective in treating AML.
• Ability to comprehend the investigational nature of the study and provide written informed consent
• Age 18 to ≤ 65 years (yrs), at the time of consent
• All gender identities, races, or ethnicities are eligible
• Newly documented, previously untreated diagnosis of AML or myelodysplastic syndrome (MDS) with marrow blasts ≥ 10%, in agreement with 2022 European LeukemiaNet criteria (ELN22)
‣ Leukapheresis and treatment with cytarabine or hydroxyurea prior to study initiation is permitted for cytoreduction in patients with proliferative disease. NOTE: Treatment with cytarabine is limited to up to 2 grams total at least 14 days prior to starting on protocol defined therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Willingness to undergo hematopoietic stem cell transplant (HSCT)
• Ability to take medications by mouth or feeding tube
• Adequate hematologic and organ function
• Institutional standards, New York Heart Association (NYHA) criteria for cardiac function
• Calculated creatinine clearance (according to the Cockcroft-Gault equation) \> 40 mL/min
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 3 x upper limit of normal (ULN), unless considered due to leukemic involvement
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x ULN, unless considered due to leukemic involvement
• Total bilirubin ≤ 1.5 x ULN, unless due to Gilbert's disease or leukemic involvement
• Willing and able to
‣ Adhere to study schedule of activities and lifestyle restrictions while on treatment;
⁃ Provide bone marrow (BM) aspirate and core biopsy samples; AND
⁃ Accept supportive and prophylactic care for hematologic toxicities, infection, and immediate sequelae, including transfusions
• Negative pregnancy test within 3 days of start of treatment for persons of childbearing potential (PCBP)
• Based on animal studies and the known pharmacology of the study drugs, PCBP and sperm-producing participants who are sexually active with a PCBP must comply with study requirements for contraception
‣ PCBP (participants and PCBP partners of participants) must agree to use an approved contraception and to refrain from donating / cryopreserving ova from cycle (C) 1 day (D) 1 until 6 months following the last dose of study treatment
⁃ Participants who produce viable sperm and who have intercourse with PCBP must agree to use an approved contraception method and to refrain from donating sperm from C1D1 until 3 months following the last dose of study treatment