VNP40101M in Treating Patients With Relapsed or Refractory Leukemia or Myelodysplastic Syndrome

A Phase I Trial Of VNP40101M, A Novel Alkylating Agent, For Patients With Hematologic Malignancies

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of VNP40101M in treating patients who have relapsed or refractory leukemia or myelodysplastic syndrome.

OBJECTIVES:

• Determine the toxic effects of VNP40101M in patients with relapsed or refractory leukemia or poor-risk myelodysplastic syndromes.
• Determine the maximum tolerated dose of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Determine the antitumor effects of this drug in these patients.

OUTLINE: Patients receive VNP40101M IV over 15 minutes once every 4 weeks.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Relapsed or refractory leukemia for which no standard therapy is anticipated to result in a durable remission OR
• Poor-risk myelodysplastic syndromes

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 3 times ULN

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

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

Other

• No uncontrolled active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior biologic therapy allowed

Chemotherapy

• At least 2 weeks since prior myelosuppressive cytotoxic chemotherapy in the absence of rapidly progressing disease
• At least 48 hours since prior hydroxyurea

Endocrine therapy

• Not specified

Radiotherapy

• Prior radiotherapy allowed

Surgery

• Not specified

Other

• No other concurrent standard or investigational treatment for leukemia
• No concurrent disulfiram