Study to Evaluate Safety, Tolerability, Maximum Tolerated Dose (MTD), Efficacy, and Pharmacokinetics (PKs) of CPI-613 Given Twice Weekly for Three Consecutive Weeks in Patients With Advanced Hematologic Malignancies

NCT01034475 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: IRB00012124CCCWFU 29109
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Chemotherapy resistance is a major cause of death in patients with advanced hematologic malignancies. The proposed novel mechanism of action, non-cross resistance with chemotherapeutic agents currently used in the clinic, and lack of CPI-613-related myelosuppression preclinically and clinically to date make CPI-613 a suitable candidate for phase I clinical trial in these patients. The current trial is one of several clinical trials of CPI-613. Other clinical trials that are conducted in patients with solid tumors have already been initiated. The primary objective of this study is to determine the safety and MTD of CPI-613 when administered 2x weekly for 3 consecutive weeks. The secondary objective is to determine the PKs of CPI-613 following IV administration and to observe the anti-tumor effects of CPI-613, if any occur.

Conditions

Advanced Hematologic Malignancies

Keywords

acute myeloid leukemia; acute lymphoblastic leukemia; multiple myeloma; chronic myeloid\ leukemia in blast phase

Outcome Measures

Primary Outcomes (1)

• To determine the safety and MTD of CPI-613 when administered 2x weekly for 3 consecutive weeks.

  3 weeks

Secondary Outcomes (1)

• To determine PKs of CPI-613 following IV administration.

  3 weeks

Study Arms (1)

CPI-613

EXPERIMENTAL

CPI-240 mg/m2

Drug: CPI-613

Interventions

CPI-613 DRUG

This is a Phase I open label trial using a 2-stage dose-escalation scheme (single-patient \& traditional stages): Single-Patient Dose-Escalation Stage: In the single-patient stage, a single patient will be accrued per dose level. The starting dose will be 420 mg/m². Dose level will be escalated (by doubling the previous dose) if there is no toxicity or if the toxicity is grade 1 or less. If toxicity is \>Grade 1, the traditional dose-escalation stage will be triggered. Traditional Dose-Escalation: All dose escalations conducted in this Traditional Dose-Escalation stage will be escalated according to the modified Fibonacci Dose-Escalation scheme.

CPI-613

Eligibility Criteria

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

You may qualify if:

• histologically or cytologically documented relapsed and/or refractory hematologic malignancy
• Karnofsky Performance Status (KPS) of \>70%.
• Must be ≥18 years of age.
• Expected survival \>1 month.
• Women of child-bearing potential must use accepted contraceptive methods
• No radiotherapy, treatment with cytotoxic agents (except CPI-613), treatment with biologic agents or any anti-cancer therapy within the 3 weeks prior to treatment with CPI-613.

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, 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 because the potential of excretion of CPI-613 into breast milk.
• Life expectancy less than 1 month.
• Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27012, United States

Location

Related Publications (1)

• Pardee TS, Lee K, Luddy J, Maturo C, Rodriguez R, Isom S, Miller LD, Stadelman KM, Levitan D, Hurd D, Ellis LR, Harrelson R, Manuel M, Dralle S, Lyerly S, Powell BL. A phase I study of the first-in-class antimitochondrial metabolism agent, CPI-613, in patients with advanced hematologic malignancies. Clin Cancer Res. 2014 Oct 15;20(20):5255-64. doi: 10.1158/1078-0432.CCR-14-1019. Epub 2014 Aug 27.

  PMID: 25165100 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Multiple Myeloma

Interventions

devimistat

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

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: December 16, 2009
• First Posted: December 17, 2009
• Study Start: March 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: August 1, 2014
• Last Updated: July 2, 2018

Record last verified: 2018-06

Locations

US (1)