CPI-613 and Hydroxychloroquine in Treating Patients with Recurrent High Risk Myelodysplastic Syndrome

Inclusion Criteria

• Histologically documented high risk MDS whose disease has failed to respond, progressed or relapsed while on a hypomethylating agent.
• International Prognostic Scoring System risk (IPSS-R) score of intermediate, high or very high at time of enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 3.
• Expected survival > 2 months.
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation.
• Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists.
• Patients must have fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities. Patients with persisting, non-hematologic, non-infectious toxicities from prior treatment =< grade 2 are eligible, but must be documented as such.
• Aspartate aminotransferase (AST / serum glutamic-oxaloacetic transaminase [SGOT]) =< 3 x upper normal limit (UNL) (obtained =< 2 weeks prior to enrollment).
• Alanine aminotransferase (ALT / serum glutamate pyruvate transaminase [SGPT]) =< 3 x UNL (obtained =< 2 weeks prior to enrollment).
• Bilirubin =< 1.5 x UNL (obtained =< 2 weeks prior to enrollment).
• Serum creatinine =< 1.5 x mg/dL or 133 umol/L (obtained =< 2 weeks prior to enrollment).
• Albumin >= 2.0 g/dL or >= 20 g/L (obtained =< 2 weeks prior to enrollment).
• Mentally competent, ability to understand and willingness to sign an Institutional Review Board (IRB)-approved written informed consent form.
• Have access via central line (e.g., portacath).

Exclusion Criteria

• Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, symptomatic coronary artery disease, myocardial infarction within the past 3 months, uncontrolled cardiac arrhythmia, pericardial disease or New York Heart Association class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients’ risk for toxicity.
• Patients with active central nervous system (CNS) or epidural tumor.
• Any active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease).
• Any condition or abnormality which may, in the opinion of the investigator, compromise his or her safety.
• Pregnant women, or women of child-bearing potential not using reliable means of contraception.
• Fertile men unwilling to practice contraceptive methods during the study period.
• Lactating females.
• Life expectancy less than 2 months.
• Unwilling or unable to follow protocol requirements.
• Evidence of ongoing uncontrolled serious infection.
• Requirement for immediate palliative treatment of any kind including surgery.
• Patients with uncontrolled human immunodeficiency virus (HIV) infection. * Note: Patients with known HIV infection are excluded because patients with an immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, and because there may be unknown or dangerous drug interactions between CPI-613 and anti-retroviral agents used to treat HIV infections.
• Patients who have received radiotherapy, surgery, treatment with cytotoxic agents (except a hypomethylating agent, i.e. azacytidine or decitabine), treatment with biologic agents, immunotherapy, or any other anti-cancer therapy of any kind, or any other standard or investigational treatment for their cancer, or any other investigational agent for any indication, within the past 2 weeks prior to initiation of CPI-613 treatment.
• Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months.