A Phase 1b/2 Open-label, Dose-ranging Safety and Efficacy Study of Oral Cladribine in Patients With Acute Myeloid Leukemia (AML)

The goal of Part 1 of this clinical research study is to find the highest tolerable dose of cladribine that can be given in combination with low dose cytarabine (LDAC) and venetoclax to patients who have AML. The goal of Part 2 of this clinical research study is to learn if the dose of cladribine found in Part 1, when combined with LDAC and venetoclax, can help to control the disease.

Inclusion Criteria: 1. Provision of written informed consent prior to any study related procedures. 2. Disease characteristics, defined as: Part 1: Dose-escalation cohorts: Patients with relapsed and/or refractory AML. Part 2: Cohort A: Patients aged .18 years with newly diagnosed ts-AML, defined as patients with prior diagnosis of MDS, treated with hypomethylating agents who have then progressed to AML. Prior therapy with hydroxyurea, hematopoietic growth factors, HMA, ATRA, or a total dose of cytarabine up to 2g (for emergency use for stabilization) is allowed. Cohort B: Patients aged . 60 years with newly diagnosed AML with monocytic phenotype, defined as AML-M5 by FAB or flow cytometry, and/or patients . 60 years with newly diagnosed AML with RAS mutations. Patients aged \< 60 years who are unsuitable for standard induction therapy may be eligible after discussion with primary investigator. 3. Adequate renal and hepatic organ function as indicated by the following laboratory values: * Serum creatinine . 2.0xupper limit of normal (ULN) * Serum total bilirubin .2xULN (with the exception of patients with known Gilbert's syndrome: serum total bilirubin must be \