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

Inclusion Criteria:

* Patients must have histologically or cytologically documented relapsed and/or refractory acute myeloid leukemia
* 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 because the effects of CPI-613 on a fetus are unknown)
* 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; 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 upper limit of normal \[ULN\] if liver metastases present)
* Bilirubin =\< 1.5 x UNL
* Serum creatinine =\< 1.5 mg/dL or 133 μmol/L
* International Normalized Ratio or INR must be \< 1.5

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
* 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 (because the teratogenic potential of CPI-613 is unknown)
* Lactating females because the potential of excretion of CPI-613 into breast milk (Note: Lactating females are excluded because the effects of CPI-613 on a nursing child are unknown)
* 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 myocardial infarction within previous 6 months, symptomatic coronary artery disease, uncontrolled arrhythmias, or symptomatic congestive heart failure
* Albumin \< 2.0 g/dL or \< 20 g/L
* Evidence of ongoing, uncontrolled infection
* Patients with known 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 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
* A history of additional risk factors for torsade de pointes (e.g., clinically significant heart failure, hypokalemia, family history of long QT syndrome)