Combination Chemotherapy in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma

Phase II CCOP Trial of High Dose Methotrexate/ARA-C and HCVAD for Newly Diagnosed Nodular and Diffuse Mantle Cell Lymphoma and Their Blastic Variants

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of different regimens of combination chemotherapy in treating patients with newly diagnosed mantle cell lymphoma.

OBJECTIVES: Evaluate the complete response rate and duration of response in patients with newly diagnosed diffuse or nodular mantle cell lymphoma or their blastic variant treated with high-dose methotrexate and cytarabine and high-dose cyclophosphamide, dexamethasone, doxorubicin, and vincristine (HCVAD). OUTLINE: This is a multicenter study. Patients may receive either regimen A or both regimen A and regimen B, depending upon response. Regimen A: Patients receive methotrexate IV over 24 hours on day 1. Cytarabine is administered IV over 2 hours every 12 hours on days 2 and 3. Filgrastim (G-CSF) is administered subcutaneously (SC) daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for up to 8 courses. Regimen B: Patients receive cyclophosphamide IV over 3 hours every 12 hours on days 1-3. Doxorubicin is administered IV over 24 hours on days 4 and 5. Vincristine is administered IV over 30 minutes on days 4 and 11. Dexamethasone is administered orally or IV on days 1-4 and 11-14. G-CSF is administered SC beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for up to 7 courses. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 21-45 patients will be accrued for this study within 4 years.

stage I mantle cell lymphoma, contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma

Methotrexate IV over 24 hours on day 1. Cytarabine is administered IV over 2 hours every 12 hours on days 2 and 3. Filgrastim (G-CSF) is administered subcutaneously (SC) daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for up to 8 courses.

Cyclophosphamide IV over 3 hours every 12 hours on days 1-3. Doxorubicin is administered IV over 24 hours on days 4 and 5. Vincristine is administered IV over 30 minutes on days 4 and 11. Dexamethasone is administered orally or IV on days 1-4 and 11-14. G-CSF is administered SC beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for up to 7 courses.

DISEASE CHARACTERISTICS: Histologically confirmed previously untreated nodular or diffuse mantle cell lymphoma or their blastic variant No CNS involvement Not a candidate for stem cell transplantation or refuses one PATIENT CHARACTERISTICS: Age: 16 and over Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 1,000/mm^3* Platelet count greater than 100,000/mm^3* NOTE: * Unless lymphoma involvement Hepatic: Bilirubin less than 1.5 mg/dL (unless lymphoma involvement) Renal: Creatinine less than 2.0 mg/dL (unless lymphoma involvement) Cardiovascular: Cardiac ejection fraction at least 50% (for patients over age 40) Other: Must be willing to receive blood transfusion Not pregnant or nursing Fertile patients must use effective contraception HIV negative No other co-morbid medical or psychiatric illness that would preclude treatment No prior or concurrent malignancy with poor prognosis (less than 90% probability of survival at 5 years) PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified