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

NCT01768897 | Completed Phase 1 FDA Drug

• 4 other identifiers: IRB00022138NCI-2012-02768P30CA012197CCCWFU 22112
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief 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

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

Outcome Measures

Primary Outcomes (1)

• MTD of CPI-613 based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 3.0)

  14 days

Secondary Outcomes (2)

• Response rate (CR, CRi, and PR)

  Day 14 of course 1

• Overall survival

  Up to 6 months

Study Arms (1)

Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)

EXPERIMENTAL

Patients receive CPI-613 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.

Drug: CPI-613; Drug: cytarabine; Drug: mitoxantrone hydrochloride; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

CPI-613 DRUG

Given IV

Also known as: alpha-lipoic acid analogue CPI-613

Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)

mitoxantrone hydrochloride DRUG

Given IV

Also known as: CL 232315, DHAD, DHAQ, Novantrone

Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)

laboratory biomarker analysis OTHER

Optional correlative studies

Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Congenital Abnormalities; Leukemia, Myeloid, Acute

Interventions

devimistat; Cytarabine; Mitoxantrone

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds

Study Officials

• Timothy Pardee

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2013
• First Posted: January 16, 2013
• Study Start: January 1, 2013
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: July 3, 2018

Record last verified: 2018-06

Locations

US (1)