Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	Pharmaceutical / Industry	VION-CLI-033 NCT00083187

Objectives

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

Entry Criteria

Disease Characteristics:

• 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]

Prior/Concurrent Therapy:

Biologic therapy

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

Chemotherapy

• 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

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

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

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• 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

Other

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

Expected Enrollment

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.

Outcomes

Complete response rate
Toxic effects
Pharmacokinetics

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 .

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.

Giles F, Rizzieri D, Karp J, et al.: Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia. J Clin Oncol 25 (1): 25-31, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Vion Pharmaceuticals, Incorporated

Francis Giles, MD, Protocol chair		Ph: 713-792-7305; 800-392-1611 Email: fgiles@mdanderson.org

Registry Information
Official Title		A Phase II Study of VNP40101M For Patients With Acute Myelogenous Leukemia Or High-Risk Myelodysplasia
Trial Start Date		2005-11-15
Trial Completion Date		2007-01-31
Registered in ClinicalTrials.gov		NCT00083187
Date Submitted to PDQ		2004-04-05
Information Last Verified		2008-08-22

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