RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy such as flavopiridol and fludarabine use different ways to stop cancer cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects, best way to give, and the best dose of flavopiridol when given together with fludarabine and rituximab in treating patients with previously untreated or relapsed lymphoproliferative disorders or mantle cell lymphoma.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of flavopiridol in combination with standard-dose rituximab and fludarabine in patients with indolent B-cell lymphoproliferative disorders or mantle cell lymphoma.
• Determine the toxicity of this regimen in these patients.
• Determine the safety, toxicity, and efficacy of administering flavopiridol as a 30-minute bolus followed by a 4-hour infusion in patients treated with this regimen.

Secondary

• Determine the pharmacokinetics and pharmacodynamics of this regimen in these patients.

OUTLINE: This is a dose-escalation study of flavopiridol.

Patients receive fludarabine IV over 15-30 minutes on days 1-5 and rituximab IV over 3-4 hours on day 1.

Flavopiridol is administered IV over 60 minutes on day 1 in cohort 1; on days 1 and 2 in cohort 2; and on days 1, 2, and 3 in cohort 3. In cohorts 4 and 5, patients receive fludarabine and rituximab as above and flavopiridol IV over 30 minutes and then IV over 4 hours on day 1 of courses 2-6. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

A total of 10-12 patients are treated with flavopiridol at the maximum tolerated dose.

PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.

• Leukemia
• Lymphoma

• Biological: rituximab
• Drug: alvocidib
• Drug: fludarabine phosphate

DISEASE CHARACTERISTICS:

• Histologically confirmed mantle cell lymphoma OR indolent B-cell lymphoproliferative disorders of any of the following types:

  • Chronic lymphocytic leukemia
  • Small lymphocytic lymphoma
  • Follicular center cell non-Hodgkin's lymphoma (grade I or II)
  • Marginal zone lymphoma
  • Waldenstrom's macroglobulinemia
  • Hairy cell leukemia
• Previously untreated or relapsed/refractory disease
• No evidence of histological transformation to an intermediate-grade or aggressive lymphoma
• CD20 positive by immunoperoxidase or flow cytometry

• Evaluable disease with presence of 1 of the following criteria:

  • Absolute lymphocyte count greater than 5,000/mm^3
  • At least 1 measurable node greater than 2 cm by CT scan OR measurable disease in a lymphoid structure (spleen)
  • Bone marrow involvement (greater than 20% of marrow cellularity)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count at least 1,500/mm^3*
• Platelet count at least 100,000/mm^3*
• Hemoglobin at least 9.0 g/dL* NOTE: *Unless due to hematologic malignancy

Hepatic

• Bilirubin no greater than 2 times normal
• AST no greater than 2 times normal

Renal

• Creatinine no greater than 2.0 mg/dL OR
• Creatinine clearance at least 50 mL/min
• No renal dysfunction that would impair tolerance or compliance with study therapy

Cardiovascular

• No cardiac dysfunction that would impair tolerance or compliance with study therapy

Pulmonary

• No pulmonary dysfunction that would impair tolerance or compliance with study therapy

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No chronic gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, short gut syndrome) that would impair tolerability of compliance with therapy
• No neurological or psychiatric dysfunction that would impair tolerability of or compliance with study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 6 weeks since prior nitrosourea or mitomycin
• No more than 6 prior courses of fludarabine

Endocrine therapy

• No concurrent corticosteroids as antiemetics

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• At least 4 weeks since prior therapy for disease
• No more than 3 prior treatments for disease (not including steroids alone)