BCL2i CLAG-M in R/R Acute Myeloid Leukemia

Exclusion Criteria

• •Venetoclax-refractory disease or recent venetoclax exposure \< 3 months prior to first dose of study therapy.
• •Prior treatment with a high-dose cytarabine-containing regimen (e.g., no prior CLAG/FLAG/MEC/CLIA/HAM, etc.).
• •Allogeneic stem cell transplant in the past 3 months.
• •Less than 14 days from last AML-directed therapy or five half-lives, whichever is shorter, not including hydroxyurea.
• •Known history of prior TP53 mutation (results from any myeloid mutation panel are not required for screening eligibility).
• •Active CNS involvement by AML.
• •WBC count ≥25k at the time study treatment begins.
• •Uncontrolled intercurrent systemic illness that would limit compliance.
• •Concurrent malignancy in addition to AML that requires active treatment with some exceptions.
• •Immunosuppressive therapy in the past 14 days except for prednisone at ≤ 10 mg/day or equivalent AND no active or uncontrolled graft-versus-host disease (GvHD).
• •Participants who have not recovered from adverse events (Aes) due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1), with the exception of alopecia.
• •Participants who are receiving any other investigational agents.
• •Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• •Patients with active heart disease that limits the use of mitoxantrone or recent (\<6 months) history of an acute cardiovascular event (STEMI, NSTEMI).
• •Pregnant women are excluded from this study because venetoclax, cladribine, and cytarabine are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these drugs, breastfeeding should be discontinued.