Temozolomide and VNP40101M in Treating Patients With Relapsed or Refractory Leukemias

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00098436
Recruitment Status : Completed
First Posted : December 8, 2004
Last Update Posted : July 18, 2013
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Leukemia Drug: laromustine Drug: temozolomide Phase 1

Detailed Description:


  • 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  (Clinical Trial)
Estimated Enrollment : 25 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study Of Cloretazine™ (VNP40101M) And Temozolomide In Patients With Hematologic Malignancies
Study Start Date : September 2004
Actual Primary Completion Date : October 2006
Actual Study Completion Date : August 2008

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • Not specified


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


  • Creatinine ≤ 2.0 mg/dL


  • 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


  • 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


Biologic therapy

  • Not specified


  • 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


  • Not specified


  • Not specified


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00098436

United States, Indiana
American Health Network - North Illinois Street
Indianapolis, Indiana, United States, 46202
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Vion Pharmaceuticals
Study Chair: Bonny L. Johnson, RN, MSN Vion Pharmaceuticals

Publications of Results: Identifier: NCT00098436     History of Changes
Other Study ID Numbers: VION-CLI-036
CDR0000405825 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: December 8, 2004    Key Record Dates
Last Update Posted: July 18, 2013
Last Verified: August 2008

Keywords provided by National Cancer Institute (NCI):
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
blastic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents