cpi-613, cytarabine, and mitoxantrone hydrochloride in treating patients with relapsed or refractory acute myeloid leukemia

Conditions: Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia

Summary: this phase i trial studies the side effects and best dose of cpi-613 when given together with cytarabine and mitoxantrone hydrochloride in treating patients with relapsed or refractory acute myeloid leukemia. drugs used in chemotherapy, such as cpi-613, cytarabine and mitoxantrone hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. cpi-613 may help cytarabine and mitoxantrone hydrochloride work better by making cancer cells more sensitive to the drugs

primary objectives: i. to determine the safety and maximum tolerated dose (mtd) of cpi-613 when administered with high dose cytarabine, and mitoxantrone (mitoxantrone hydrochloride). secondary objectives: i. to determine the pharmacokinetics (pks) of cpi-613 following intravenous (iv) administration in combination with high dose cytarabine and mitoxantrone. ii. to observe the response rate (complete response \[cr\], complete response with incomplete platelet recovery \[cri\] and partial response \[pr\]) of cpi-613 in combination with high dose cytarabine and mitoxantrone. iii. to observe the overall survival of patients treated with cpi-613 in combination with high dose cytarabine and mitoxantrone. outline: this is a dose-escalation study of cpi-613. patients receive cpi-613 intravenously (iv) over 2 hours on days 1-5, cytarabine iv over 3 hours every 12 hours for 5 doses beginning on day 3, and mitoxantrone hydrochloride iv over 15 minutes after the 1st, 3rd, and 5th doses of cytarabine. . treatment repeats every 14 days for up to 2 courses\* in the absence of disease progression or unacceptable toxicity. note: \*patients undergoing a second course of therapy receive cpi-613 iv over 2 hours on days 1-3, cytarabine iv over 3 hours every 12 hours for 5 doses beginning on day 2, and mitoxantrone hydrochloride iv over 15 minutes after the 1st and 3rd doses of cytarabine. after completion of study treatment, patients are followed up for 6 months.

Eligibility criteria:
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)