CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients with Relapsed or Refractory Acute Myeloid Leukemia or Granulocytic Sarcoma

Inclusion Criteria

• Patients must have histologically or cytologically documented relapsed and/or refractory acute myeloid leukemia or granulocytic sarcoma
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 3
• Expected survival > 3 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), and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation; (Note: pregnant patients are excluded)
• Fertile men must practice effective contraceptive methods during the study period, unless documentation of infertility exists
• Mentally competent, ability to understand and willingness to sign the informed consent form
• No radiotherapy, treatment with cytotoxic agents (except CPI-613), treatment with biologic agents or any anti-cancer therapy within the 2 weeks prior to treatment with CPI-613; hydroxyurea and oral tyrosine kinase inhibitors being used without grade =< 2 toxicity can be taken until day 1 of therapy; 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 (returned to baseline status as noted before most recent treatment); 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), alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3 x UNL (=< 5 x ULN if liver metastases present)
• Bilirubin =< 1.5 x UNL
• Serum creatinine =< 1.5 mg/dL or 133 umol/L
• Left ventricular ejection fraction (by transthoracic echocardiography [TTE], multigated acquisition scan [MUGA] or cardiac magnetic resonance imaging [MRI]) sufficient to safely administer mitoxantrone as determined by the treating physician

Exclusion Criteria

• Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 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
• Albumin < 2.0 g/dL or < 20 g/L
• Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
• Pregnant women, or women of child-bearing potential not using reliable means of contraception
• Lactating females
• Fertile men unwilling to practice contraceptive methods during the study period
• Life expectancy less than 3 months
• Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
• Unwilling or unable to follow protocol requirements
• Patients with large and recurrent pleural or peritoneal effusions requiring frequent drainage (e.g. weekly); patients with any amount of clinically significant pericardial effusion
• Active heart disease including symptomatic coronary artery disease, uncontrolled arrhythmias, or symptomatic congestive heart failure
• Evidence of ongoing, uncontrolled infection
• Patients with known human immunodeficiency virus (HIV) infection
• Patients receiving 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 (the use of Hydrea is allowed)
• Patients who have received immunotherapy of any type within the past 4 weeks prior to initiation of CPI-613 treatment
• Requirement for immediate palliative treatment of any kind including surgery
• Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months