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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Comprehensive Cancer Center of Wake Forest University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT01768897
First received: January 11, 2013
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
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
Drug: CPI-613
Drug: cytarabine
Drug: mitoxantrone hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Dose-Escalation Study to Evaluate Safety, Tolerability, Maximum Tolerated Dose (MTD), Efficacy, and Pharmacokinetics (PKs) of CPI-613 Given With High Dose Cytarabine and Mitoxantrone in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:
  • MTD of CPI-613 based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 3.0) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response rate (CR, CRi, and PR) [ Time Frame: Day 14 of course 1 ] [ Designated as safety issue: No ]
    Confidence intervals will be calculated.

  • Overall survival [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    We will use Kaplan-Meier estimation.


Estimated Enrollment: 20
Study Start Date: January 2013
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: CPI-613
Given IV
Other Names:
  • alpha-lipoic acid analogue CPI-613
  • CPI-613
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: mitoxantrone hydrochloride
Given IV
Other Names:
  • CL 232315
  • DHAD
  • DHAQ
  • Novantrone
Other: laboratory biomarker analysis
Optional correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  • Troponin I above institutional limit of normal
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01768897

Locations
United States, North Carolina
Comprehensive Cancer Center of Wake Forest University Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Timothy S. Pardee    336-713-6771    tspardee@wfubmc.edu   
Principal Investigator: Timothy S. Pardee         
Sponsors and Collaborators
Comprehensive Cancer Center of Wake Forest University
Investigators
Principal Investigator: Timothy Pardee Comprehensive Cancer Center of Wake Forest University
  More Information

No publications provided

Responsible Party: Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier: NCT01768897     History of Changes
Other Study ID Numbers: CCCWFU 22112, NCI-2012-02768, P30CA012197
Study First Received: January 11, 2013
Last Updated: January 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Mitoxantrone
Thioctic Acid
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antioxidants
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 26, 2014