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

• Status: Completed
• Trial end date: 2016-01-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Wake Forest University Health Sciences
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cytarabine; Mitoxantrone; Thioctic Acid

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)