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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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)