CPI-613 in Treating Patients With Myelodysplastic Syndromes Who Failed Previous Therapy

A Pilot Study of CPI-613 in Patients With Myelodysplastic Syndrome Who Have Failed Previous Therapy

This pilot clinical trial studies 6, 8-bis (benzylthio) octanoic acid (CPI-613) in treating patients with myelodysplastic syndromes who failed previous therapy. Sometimes when chemotherapy or biological therapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to treatment. 6, 8-bis (benzylthio) octanoic acid may interfere with the growth of tumor cells and may be an effective treatment for myelodysplastic syndromes that did not respond to previous therapy.

Study Overview

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and anti-cancer activities of CPI-613 in myelodysplastic syndrome (MDS) patients who have failed previous agents (such as decitabine [Dacogen], azacitidine [Vidaza], growth factors or lenalidomide).

OUTLINE:

Patients receive 6, 8-bis (benzylthio) octanoic acid intravenously (IV) over 2 hours on days 1 and 4 of weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Comprehensive Cancer Center of Wake Forest University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically documented MDS of any risk group that has failed previous therapy (therapy failure is defined as patients who have been sufficiently treated with previous agents without response in the opinion of the treating physician, or whose disease has progressed or relapsed while on a hypomethylating agent)
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 3
  • Expected survival > 2 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) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation
  • Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists
  • 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; 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 (=< 5x ULN if liver metastases present)
  • Bilirubin =< 1.5 x UNL
  • Serum creatinine =< 1.5 mg/dL or 133 umol/L
  • International normalized ratio (or INR) must be < 1.5
  • Albumin >= 2.0 g/dL or >= 20 g/L
  • Mentally competent, ability to understand and willingness to sign an Institutional Review Board (IRB)-approved written informed consent form
  • Have access via central line (e.g., portacath)

Exclusion Criteria:

  • Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, coronary artery disease, myocardial infarction within the past 3 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 or bleeding diathesis (e.g., active peptic ulcer disease)
  • Any condition or abnormality which may, in the opinion of the investigator, compromise his or her safety
  • Pregnant women, or women of child-bearing potential not using reliable means of contraception
  • Fertile men unwilling to practice contraceptive methods during the study period
  • Lactating females
  • Life expectancy less than 2 months
  • Unwilling or unable to follow protocol requirements
  • A history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome, etc.)
  • Evidence of active infection or serious infection within the past month
  • Requirement for immediate palliative treatment of any kind including surgery
  • Prior illicit drug addiction
  • Patients with large and recurrent pleural or peritoneal effusions requiring frequent drainage (e.g. weekly)
  • Patients with any amount of clinically significant pericardial effusion
  • 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 who have received radiotherapy, surgery, treatment with cytotoxic agents (except CPI-613), treatment with biologic agents, immunotherapy, or any other anti-cancer therapy of any kind, or 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
  • Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (6, 8-bis(benzylthio) octanoic acid)
Patients receive treatment 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1 and 4 of weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Given IV
Other Names:
  • CPI-613
  • alpha-lipoic acid analogue CPI-613

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate (RR), defined as the combined rate of complete remission (CR), marrow CR, partial remission (PR), or stable disease (SD), as described by Cheson, et al. (2006)
Time Frame: Up to 5 years
Proportion of RR (along with a 95% confidence interval) of patients who respond will be presented.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety profile of CPI-613, based on evaluation of symptoms, vital signs, ECOG performance status and survival, clinical chemistry, hematology, and coagulation, assessed by National Cancer Institute Common Terminology Criteria for Adverse Events v 4.0
Time Frame: Up to 1 month post-treatment
Toxicities will be examined by looking at each toxicity identified by grade.
Up to 1 month post-treatment
Progression-free survival (PFS)
Time Frame: Up to 5 years
Survival curves for PFS using Kaplan-Meier techniques will be estimated. In addition, the 6 month and 1-year PFS rates for these participants will be estimated.
Up to 5 years
Overall survival (OS)
Time Frame: Up to 5 years
Survival curves for OS using Kaplan-Meier techniques will be estimated. In addition, the 6 month and 1-year OS rates for these participants will be estimated.
Up to 5 years
Number of patients who achieve a reduction in blood transfusion requirements
Time Frame: Up to 5 years
Up to 5 years
Number of patients who achieve hematologic improvement (HI), as defined by Cheson, et al. (2006)
Time Frame: Up to 5 years
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Timothy Pardee, Wake Forest University Health Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2013

Primary Completion (Actual)

November 26, 2018

Study Completion (Actual)

November 26, 2018

Study Registration Dates

First Submitted

July 15, 2013

First Submitted That Met QC Criteria

July 15, 2013

First Posted (Estimate)

July 18, 2013

Study Record Updates

Last Update Posted (Actual)

July 2, 2021

Last Update Submitted That Met QC Criteria

July 1, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Other Study ID Numbers

  • IRB00024007
  • P30CA012197 (U.S. NIH Grant/Contract)
  • NCI-2013-01312 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • CCCWFU 29113 (Other Identifier: Wake Forest University Health Sciences)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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