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VNP40101M in Treating Patients With Acute Myelogenous Leukemia or High-Risk Myelodysplasia

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: NCT00083187
Recruitment Status : Completed
First Posted : May 17, 2004
Last Update Posted : July 18, 2013
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as VNP40101M and hydroxyurea, work in different ways to stop cancer cells from dividing so they stop growing or die. Hydroxyurea may help VNP40101M kill more cancer cells by making cancer cells more sensitive to the drug.

PURPOSE: This phase II trial is studying how well giving VNP40101M with hydroxyurea works in treating patients with acute myelogenous leukemia or high-risk myelodysplasia.

Condition or disease Intervention/treatment Phase
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms Drug: hydroxyurea Drug: laromustine Phase 2

Detailed Description:


  • Determine the complete response rate to VNP40101M in patients with acute myelogenous leukemia or high-risk myelodysplasia .
  • Determine the toxic effects of this regimen in these patients.
  • Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study. Patients are stratified to acute myelogenous leukemia (AML) or high risk myelodysplasia (MDS) patients ≥ 60 years old with no prior treatment vs AML patients any age in first relapse. (AML patients any age in first relapse closed to accrual 06/09/05).

Patients receive VNP40101M IV over 30 minutes once on day 1 (course 1).

Four to five weeks after the first course, patients undergo bone marrow aspiration and biopsy. If the bone marrow is improved but contains residual leukemia, patients receive a second course of VNP40101M (at the same dose as in course 1). If patients achieve complete response (CR), or partial CR after the first or second course, a consolidation course may be given comprising VNP40101M at a reduced dose.

Patients are followed monthly for 6 months, every 2 months for 12 months, and then every 3 months for 18 months .

PROJECTED ACCRUAL: A total of 230 patients (100 with acute myelogenous leukemia (AML) or high-risk myelodysplasia and 130 with AML in first relapse) will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of VNP40101M For Patients With Acute Myelogenous Leukemia Or High-Risk Myelodysplasia
Study Start Date : November 2005
Actual Primary Completion Date : January 2007
Actual Study Completion Date : August 2008

Primary Outcome Measures :
  1. Complete response rate
  2. Toxic effects
  3. Pharmacokinetics

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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


  • Histologically confirmed diagnosis of 1 of the following:

    • Acute myelogenous leukemia (AML), meeting the following criteria:

      • In first relapse after first treatment-induced complete remission (CR) (closed to accrual as of 06/09/05)

        • Duration of first CR less than 12 months
        • No prior treatment for first relapse except hydroxyurea
      • FAB type M0, M1, M2, M4-7
      • No acute promyelocytic leukemia
      • No prior treatment with a standard induction regimen containing cytotoxic agents* (for patients 60 years of age or older)
    • High-risk myelodysplasia, meeting the following criteria:

      • 60 years of age and over
      • No prior cytotoxic chemotherapy* except hydroxyurea
      • Prior gemtuzumab ozogamicin allowed
      • High risk defined as International Prognostic Scoring System score ≥ 1.5, defined by cytogenetics, % marrow blasts, and lineage cytopenias NOTE: *Prior low-dose, single-agent cytarabine, decitabine, or azacitidine not considered prior cytotoxic chemotherapy



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • Not specified


  • Bilirubin ≤ 2.0 mg/dL
  • ALT or AST ≤ 5 times upper limit of normal
  • Chronic hepatitis allowed


  • Creatinine ≤ 2.0 mg/dL


  • No myocardial infarction within the past 3 months
  • No symptomatic coronary artery disease
  • No uncontrolled arrhythmias
  • No uncontrolled congestive heart failure
  • No other active heart disease


  • No uncontrolled active infection
  • Not pregnant or nursing
  • Fertile patients must use effective contraception


Biologic therapy

  • Up to 4 leukapheresis procedures allowed during the first 15 days of study treatment


  • See Disease Characteristics
  • Concurrent additional hydroxyurea (maximum dose of 5 g daily for up to 4 days) allowed between days 4 and 15 of each study course to control elevated blast levels

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified


  • Recovered from all prior therapy
  • At least 72 hours since prior anti-leukemic treatment with a non-cytotoxic agent
  • No concurrent disulfiram (Antabuse)
  • No other concurrent anticancer drugs except anagrelide within the first 15 days of study treatment to control elevated platelet counts
  • No other concurrent treatment for leukemia, except hydroxyurea used during study treatment
  • No other concurrent investigational drugs

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): NCT00083187

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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
Marseille, France, 13273
United Kingdom
King's College Hospital
London, England, United Kingdom, SE5 8RX
Sponsors and Collaborators
Vion Pharmaceuticals
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Study Chair: Francis J. Giles, MD M.D. Anderson Cancer Center
Publications of Results:
Gerson SL, Karp J, Rizzieri D, et al.: Low levels of pre-treatment O6-alkylguanine transferase (AGT) in patients with AML correlate with response to Cloretazine® (VNP40101M) induction therapy. [Abstract] American Association for Cancer Research: 98th Annual Meeting, April 14-18, 2007, Los Angeles, CA. A-2640, 2007.

Layout table for additonal information Identifier: NCT00083187    
Other Study ID Numbers: VION-CLI-033
CDR0000365510 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: May 17, 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
untreated adult acute myeloid leukemia
atypical chronic myeloid leukemia, BCR-ABL1 negative
chronic myelomonocytic leukemia
myelodysplastic/myeloproliferative neoplasm, unclassifiable
secondary myelodysplastic syndromes
de novo myelodysplastic syndromes
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors