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

Advanced Hematologic Malignancies Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01034475
• Other study ID #: IRB00012124
• Secondary ID: CCCWFU 29109
• Status: Completed
• Phase: Phase 1
• Start date: March 2010
• Est. completion date: August 2014

Study information

• Verified date: June 2018
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: August 2014
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Hematologic Malignancies
• Neoplasms

Intervention

Drug:
• CPI-613
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.

Locations

Country	Name	City	State
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

References & 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 pat — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the safety and MTD of CPI-613 when administered 2x weekly for 3 consecutive weeks.		3 weeks
Secondary	To determine PKs of CPI-613 following IV administration.		3 weeks