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

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 \<3xULN in these patients)
• •* Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) .2.5xULN or .5xULN if due to leukemic involvement)
• •4. Adequate cardiac function with a left ventricular ejection fraction .50%
• •5. Female participants are eligible to enter and participate in the study if they are of nonchildbearing potential. Female participants of childbearing age must use at least 2 forms of effective birth control during the study treatment period and for at least 90 days after the last dose of investigational product.
• •6. Male participants are eligible to enter and participate in the study if they agree to use effective methods of contraception during the study treatment period and for at least 90 days after the last dose of investigational product.