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

Alternate Title

VNP40101M and Cytarabine in Treating Patients With Hematologic Malignancies

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 18 and over NCI, Pharmaceutical / Industry VION-CLI-034 MDA-2003-0326, NCT00070538

Objectives

1. Determine the maximum tolerated dose of VP40101M when administered with cytarabine in patients with hematologic malignancies.
2. Determine the toxic effects of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Diagnosis of leukemia or myelodysplastic syndromes (MDS) meeting criteria for 1 of the following:
  • Relapsed or refractory leukemia for which there is no standard therapy anticipated to result in a durable remission
    • Acute myeloid leukemia
    • Acute lymphocytic leukemia
    • Chronic myelogenous leukemia
      • In blast crisis
  • Untreated leukemia and standard therapy is refused
  • Any of the following poor-risk MDS:
    • Refractory anemia with excess blasts (RAEB)
    • RAEB in transformation
    • Chronic myelomonocytic leukemia



• CNS leukemia allowed

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• At least 48 hours since prior hydroxyurea

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• At least 2 weeks since prior myelosuppressive cytotoxic agents (in the absence of rapidly progressing disease)
• No other concurrent standard or investigational treatment for leukemia
• No concurrent disulfiram

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT or AST no greater than 3 times ULN
• Chronic hepatitis allowed

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

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

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No persistent chronic toxic effects from prior chemotherapy greater than grade 1
• No uncontrolled active infection
  • Infections under control and under active treatment with antibiotics allowed

Expected Enrollment

Approximately 25 patients will be accrued for this study.

Outline

This is an open-label, dose-escalation study of VNP40101M.

Patients receive cytarabine IV over 24 hours on days 1-4 for patients under 65 years of age OR on days 1-3 for patients 65 years of age and over. Patients also receive VNP40101M IV over 15-60 minutes on day 2. Treatment repeats every 4 weeks for up to 3 courses (in patients with responding disease) in the absence of disease progression or unacceptable toxicity. Patients with a continued response may receive additional courses at the discretion of the investigator.

Cohorts of 3-6 patients receive escalating doses of VNP40101M 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 may receive treatment at the MTD.

Giles F, Verstovsek S, Thomas D, et al.: Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia. Clin Cancer Res 11 (21): 7817-24, 2005.[PUBMED Abstract]

Giles FJ, Verstovsek S, Cortes J, et al.: Phase I study of VNP40101M (101M) and AraC in patients (pts) with refractory leukemia. [Abstract] J Clin Oncol 22 (14 Suppl): A-6617, 586s, 2004.

Trial Contact Information

Trial Lead Organizations

Vion Pharmaceuticals, Incorporated

Mario Sznol, MD, Protocol chair		Ph: 203-498-4210

Registry Information
Official Title		A Phase I Study Of VNP40101M And Cytarabine For Patients With Hematologic Malignancies
Trial Start Date		2003-06-18
Trial Completion Date		2004-09-01
Registered in ClinicalTrials.gov		NCT00070538
Date Submitted to PDQ		2003-09-09
Information Last Verified		2008-08-22
NCI Grant/Contract Number		CA16672

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