Temozolomide and VNP40101M in Treating Patients With Relapsed or Refractory Leukemias

July 17, 2013 updated by: Vion Pharmaceuticals

A Phase I Study Of Cloretazine™ (VNP40101M) And Temozolomide In Patients With Hematologic Malignancies

RATIONALE: Drugs used in chemotherapy, such as temozolomide and VNP40101M, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Temozolomide may also help VNP40101M kill more cancer cells by making cancer cells more sensitive to the drug. Giving temozolomide together with VNP40101M may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of temozolomide and VNP40101M in treating patients with relapsed or refractory leukemias.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose of temozolomide and VNP40101M in patients with relapsed or refractory leukemias.
  • Determine the toxic effects of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive oral temozolomide twice daily on days 1-3 (for 5 doses) followed by VNP401010M IV over 15-60 minutes on day 3 (course 1). Patients achieving a complete or partial response or having ≥ 50% reduction in bone marrow blasts may receive a second course of therapy no earlier than day 43. Courses may be repeated approximately every 6 weeks at the discretion of the sponsor and in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of temozolomide until a dose that depletes leukemic blast AGT in at least 4 of 6 patients is determined. Once this dose is determined, cohorts of 3-6 patients receive escalating doses of VNP401010M until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 10 patients are treated at the MTD.

PROJECTED ACCRUAL: Approximately 25 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

25

Phase

  • Phase 1

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

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • American Health Network - North Illinois Street
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Center
      • Cleveland, Ohio, United States, 44106-5065
        • Case Comprehensive Cancer Center

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

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • Acute myeloid leukemia
    • Acute lymphoblastic leukemia
    • Chronic myelogenous leukemia in blast crisis
  • Relapsed or refractory disease
  • No known standard therapy that is anticipated to result in a durable remission exists
  • CNS leukemia allowed

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT or AST ≤ 3 times ULN
  • Chronic hepatitis allowed

Renal

  • Creatinine ≤ 2.0 mg/dL

Cardiovascular

  • No active heart disease, including any of the following:

    • Myocardial infarction within the past 3 months
    • Symptomatic coronary artery disease
    • Arrhythmias not controlled by medication
    • Uncontrolled congestive heart failure

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • No uncontrolled active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • Concurrent hydroxyurea allowed within the first 10 days of study drug administration for control of elevated blast levels or platelet counts

    • Maximum hydroxyurea dose 5 g daily
  • No persistent chronic toxic effects from prior chemotherapy > grade 1

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • Recovered from all prior therapy
  • At least 2 weeks since prior myelosuppressive cytotoxic agents (in the absence of rapidly progressive disease)
  • No more than 2 leukapheresis procedures within the first 10 days of study drug administration for control of elevated blast levels or platelet counts
  • No concurrent disulfiram
  • No other concurrent anticancer drugs
  • No other concurrent standard or investigational treatment for leukemia

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
  • Masking: None (Open Label)

Collaborators and Investigators

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

Sponsor

Vion Pharmaceuticals

Investigators

  • Study Chair: Bonny L. Johnson, RN, MSN, Vion Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

September 1, 2004

Primary Completion (Actual)

October 1, 2006

Study Completion (Actual)

August 1, 2008

Study Registration Dates

First Submitted

December 7, 2004

First Submitted That Met QC Criteria

December 7, 2004

First Posted (Estimate)

December 8, 2004

Study Record Updates

Last Update Posted (Estimate)

July 18, 2013

Last Update Submitted That Met QC Criteria

July 17, 2013

Last Verified

August 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VION-CLI-036
  • CDR0000405825 (Registry Identifier: PDQ (Physician Data Query))
  • CWRU-050419

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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