PK Study of Oral and IV Clofarabine in High Risk Myelodysplasia+Acute Leukemias

Inclusion Criteria: * MDS patients age 18 and older with IPSS risk of intermediate-2 who have failed ≥ 1 prior regimen with a DNA methyltransferase inhibitor, or have ≥ 10% bone marrow myeloblasts * MDS patients age 18 and older with IPSS high risk * Patients with CMML (chronic myelomonocytic leukemia) age 18 and older * Untreated AML or Ph-negative ALL patients age 60 and over who are deemed not to be candidates for intensive anthracycline based induction therapies based on age, organ function or co-morbidities * AML or Ph-negative ALL patients age 60 and over who have failed or relapsed following initial induction therapy * Provide signed written informed consent. * Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. * Have adequate renal and hepatic functions as indicated by the following laboratory values: * Serum creatinine \</= 1.0 mg/dL; if serum creatinine \>1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be \>60 mL/min as calculated by the Cockcroft-Gault equation: GFR (mL/min) = (140 - age) X (weight in kg) X (0.85 if female)/ 72 X serum creatinine in mg/mL * Serum bilirubin ≤1.5 mg/dL × upper limit of normal (ULN) * Aspartate transaminase (AST)/alanine transaminase (ALT) \</=2.5 × ULN * Alkaline phosphatase 2.5 × ULN * Female patients of childbearing potential must have a negative serum pregnancy test within 1 week prior to enrollment. * Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. * INR ≤ 1.5 and APTT within the upper limits of normal (Patients on therapeutic anticoagulation will be allowed to participate if anticoagulation can be changed to parenteral medication or discontinued when platelet count is \<50x109/liter) Exclusion Criteria: * Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol. * Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy. * Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment. * Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). * Pregnant or lactating patients. * Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. * Abnormal organ function as defined by ALT, AST or total bilirubin \>1.5 x ULN, GFR\< 60mL/minute by MDRD equation * Active cardiac disease as manifest by: \>class II NYHA congestive heart failure, unstable angina or myocardial infarction within the last 6 months * Hemorrhage or bleeding \>/= CTCAE grade 3 within 4 weeks of enrollment * Pulmonary hemorrhage \>/= CTCAE grade 2 within 4 weeks of enrollment * HIV infection * Active Hepatitis B or Hepatitis C infection (defined as measurable viral load by PCR, or liver function abnormalities attributed to viral hepatitis) * Cerebrovascular accident or transient ischemic attack within 6 months of study enrollment. * Non-healing wound or ulcer, or major surgery or trauma within 4 weeks of study enrollment * Active graft versus host disease of any grade * Active CNS disease that will require radiation therapy. * Suspected or confirmed hypersensitivity to cimetidine or other histamine H2 antagonists. * Have currently active gastrointestinal disease, or prior surgery that may affect the ability of the patient to absorb oral clofarabine. * Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy, with the following exceptions: * Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. * Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed. * Medical indication for therapy with one of the previously-documented human OCT2 inhibitors (table 4), for which cessation of the OCT2 inhibitor or conversion to an alternate agent would pose unacceptable risk to the patient