S0213 Chemotherapy Plus Rituximab in Treating Patients With Mantle Cell Lymphoma

OBJECTIVES:

• Determine the 1-year progression-free survival probability in patients with previously untreated mantle cell lymphoma treated with courses of rituximab and cyclophosphamide, doxorubicin, vincristine, and dexamethasone alternating with courses of rituximab and high-dose cytarabine and methotrexate with leucovorin calcium.
• Determine the response rate (complete unconfirmed and complete and partial responses) and survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Correlate chromosomal breakpoints, translocated immunoglobulin regulatory sequences, and cyclins D1, D2, and D3 with response and progression-free survival in patients treated with this regimen.
• Correlate gene expression (measured by DNA microarray analysis) with response and progression-free survival in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

• Courses 1, 3, 5, and 7: Patients receive rituximab IV on day 1 (courses 1, 3, and 5 only); cyclophosphamide IV over 3 hours twice a day on days 2-4; doxorubicin IV over 24 hours on days 5-7; vincristine IV on days 5 and 12; dexamethasone orally or IV four times a day on days 2-5 and 12-15; and filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 8 and continuing until blood counts recover.
• Courses 2, 4, 6, and 8: Patients receive rituximab IV on day 1 (courses 2, 4, and 6 only); high-dose methotrexate IV over 24 hours on day 2; high-dose cytarabine IV over 2 hours twice a day on days 3-4; oral leucovorin calcium 4 times a day on days 3-10; and G-CSF SC daily beginning on day 5 and continuing until blood counts recover.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed within 30 days, every 3 months for 2 years, and then every 6 months for 3 years. Patients with disease progression are followed annually for up to 5 years from study entry.

PROJECTED ACCRUAL: Approximately 50 patients will be accrued for this study within 25 months.

DISEASE CHARACTERISTICS:

• Histologically proven stage III/IV or bulky stage II mantle cell lymphoma of one of the following histologic subtypes:

• Nodular
• Diffuse
• Mantle zone
• Blastic
• Newly diagnosed and previously untreated disease
• Bidimensionally measurable disease

PATIENT CHARACTERISTICS:

Age:

• 18 to 69

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3 (50,000/mm^3 if marrow involvement present)

Hepatic:

• Bilirubin no greater than 1.5 mg/dL (5.0 mg/dL if hepatic involvement present)

Renal:

• Creatinine no greater than 2.0 mg/dL
• Creatinine clearance greater than 50 mL/min

Cardiovascular:

• Ejection fraction at least 50% by MUGA or 2-D echocardiogram
• No significant abnormalities by EKG

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• Willing to receive blood product transfusions
• No known sensitivity to E. coli-derived proteins
• No known AIDS syndrome or HIV-associated complex
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior monoclonal antibody therapy

Chemotherapy:

• No prior chemotherapy for lymphoma

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for lymphoma

Surgery:

• Not specified