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

• Status: Active, not recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This pilot phase II trial studies how well CPI-613 (6,8-bis[benzylthio]octanoic acid), cytarabine, and mitoxantrone hydrochloride work in treating patients with acute myeloid leukemia or granulocytic sarcoma (a malignant, green-colored tumor of myeloid cells [a type of immature white blood cell]) that has returned (relapsed) or that does not respond to treatment (refractory). 6,8-bis(benzylthio)octanoic acid is thought to kill cancer cells by turning off their mitochondria. Mitochondria are used by cancer cells to produce energy and are the building blocks needed to make more cancer cells. By shutting off these mitochondria, 6,8-bis(benzylthio)octanoic acid deprives the cancer cells of energy and other supplies that they need to survive and grow in the body. Drugs used in chemotherapy, such as cytarabine and mitoxantrone hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving 6,8-bis(benzylthio)octanoic acid together with cytarabine and mitoxantrone hydrochloride may kill more cancer cells.

• Phase: Phase 2
• 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 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

• 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 upper limit of normal [ULN] if liver metastases present)

• Bilirubin =< 1.5 x UNL

• Serum creatinine =< 1.5 mg/dL or 133 umol/L

• International normalized ratio or INR must be < 1.5

• 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

• 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 myocardial infarction within previous 6 months, 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

• A history of additional risk factors for torsade de pointes (e.g., clinically significant heart failure, hypokalemia, family history of long QT syndrome)