• Maximum tolerated dose (Phase I) [ Designated as safety issue: Yes ]
  
• Toxicity (Phase I) [ Designated as safety issue: Yes ]
  
• Response rate (complete response and partial response) [ Designated as safety issue: No ]
  

• Pharmacokinetics [ Designated as safety issue: No ]
  
• Incidence of tumor lysis syndrome [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Assess the response of patients with refractory or recurrent mantle cell lymphoma or diffuse large B-cell lymphoma treated with flavopiridol.
• Assess the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of this drug in these patients.

Secondary

• Determine the pharmacokinetics of this drug in these patients.
• Correlate pharmacokinetics with toxicity and the incidence of tumor lysis syndrome.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II, open-label study. Patients enrolled in the phase II portion of the study are stratified according to disease (mantle cell lymphoma vs diffuse large B-cell lymphoma).

• Phase I: Patients receive flavopiridol IV over 4½ hours once a week for 4 weeks. Treatment repeats every 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 flavopiridol 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.

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

Blood samples are collected periodically for pharmacokinetic analysis and research studies (including microarray analysis, proteomic analysis, and immunohistochemistry of markers, such as BCL-2, p53, MUM-1, BCL-6, MIB-1, and CD10). Samples are also analyzed for expression of Ki67 and by TUNEL staining.

After completion of study treatment, patients are followed every 3-4 months until disease progression and then periodically thereafter.

PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Pathologically confirmed refractory or recurrent mantle cell lymphoma OR diffuse large B-cell lymphoma (DLBCL), including any of the following:

  • Mediastinal [thymic] large B-cell lymphoma
  • Transformed large B-cell lymphoma
  • Follicular grade IIIB large B-cell lymphoma
  • Intravascular large B-cell lymphoma
• Previously treated disease

• Measurable disease, defined as one of the following:

  • Measurable disease in 2 dimensions
  • Leukemic disease that can be quantified and followed
• Prior anthracycline-based treatment required for patients with DLBCL
• No active CNS lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute neutrophil count > 1,000/mm³ (independent of transfusions)
• Platelet count > 50,000/mm³ (independent of transfusions)
• WBC ≤ 100,000/mm³
• Creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/min
• ALT < 5 times upper limit of normal
• Bilirubin < 2 mg/dL (< 5 mg/dL in patients with Gilbert's syndrome, defined as > 80% unconjugated bilirubin)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No HIV positivity
• Hepatitis B surface antigen negative
• No history of inflammatory bowel disease (unless inactive for ≥ 2 years)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from all prior therapy
• More than 4 weeks since prior systemic cytotoxic therapy
• More than 4 weeks since prior experimental treatments