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

NCT ID: NCT01768897

Last Updated: 2018-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2016-01-31

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

Detailed Description

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)

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.

Group Type: EXPERIMENTAL

CPI-613

Intervention Type: DRUG

Given IV

cytarabine

Intervention Type: DRUG

Given IV

mitoxantrone hydrochloride

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Optional correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

CPI-613

Given IV

Intervention Type: DRUG

cytarabine

Given IV

Intervention Type: DRUG

mitoxantrone hydrochloride

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Optional correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

alpha-lipoic acid analogue CPI-613; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside; CL 232315; DHAD; DHAQ; Novantrone; pharmacological studies

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy Pardee

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, United States

Countries

United States

Other Identifiers

NCI-2012-02768

Identifier Type: REGISTRY

Identifier Source: secondary_id

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CCCWFU 22112

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00022138

Identifier Type: -

Identifier Source: org_study_id