VNP40101M in Treating Patients With Richter Syndrome or Refractory or Relapsed Chronic Lymphocytic Leukemia or Other Lymphoproliferative Disorders

OBJECTIVES:

• Determine the maximum tolerated dose (MTD) of VNP40101M in patients with Richter syndrome or refractory or relapsed chronic lymphocytic leukemia or other lymphoproliferative disease. (phase I)
• Determine the toxic effects of this drug in these patients. (phase I)
• Determine the efficacy, as determined by overall response rate, of this drug at the MTD determined in phase I in these patients. (phase II)

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

• Phase I: Patients receive VNP40101M IV over 30 minutes on day 1. Courses repeat every 3-6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

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 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

• Phase II: Patients receive VNP40101M at the MTD determined in phase I.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematologic malignancies:

• Fludarabine refractory or relapsed chronic lymphocytic leukemia (CLL)

• CLL in transformation allowed
• Richter syndrome
• Other refractory lymphoproliferative diseases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Creatinine ≤ 2.0 mg/dL

• Renal dysfunction due to organ infiltration by disease allowed
• AST and ALT ≤ 3 times upper limit of normal (ULN) (unless due to organ infiltration by disease)
• Bilirubin ≤ 1.5 times ULN (unless due to Gilbert's syndrome)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• No symptomatic coronary artery disease
• No arrhythmia not controlled by medication
• No uncontrolled, symptomatic congestive heart failure
• No myocardial infarction within the past 3 months
• No other uncontrolled illness
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• At least 2 weeks since prior cytotoxic therapy except in patients with rapidly progressing disease
• No other concurrent standard or investigational treatment for this cancer
• No other concurrent cytotoxic investigational drugs
• No concurrent disulfiram