Clinical trial NCT01034475: 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
Official title: An Open Label, Dose-Escalation 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Hematologic Malignancies
Keywords: acute myeloid leukemia
acute lymphoblastic leukemia
multiple myeloma
chronic myeloid\ leukemia in blast phase
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2009-12-17
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

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, 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.

Primary outcomes:
measure: To determine the safety and MTD of CPI-613 when administered 2x weekly for 3 consecutive weeks.
timeFrame: 3 weeks
Secondary outcomes:
measure: To determine PKs of CPI-613 following IV administration.
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
References:
citation: 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.