Rituximab and Carmustine, Cytarabine, Etoposide, and Melphalan Followed By Autologous Hematopoietic Stem Cell Transplantation in Treating Patients With B-Cell Non-Hodgkin's Lymphoma

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 carmustine, cytarabine, etoposide, and melphalan, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining rituximab and combination chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining rituximab with combination chemotherapy followed by autologous hematopoietic stem cell transplantation in treating patients who have B-cell non-Hodgkin's lymphoma.

OBJECTIVES:

• Determine the levels of soluble CD20 antigen (sCD20) in the blood before and after treatment with rituximab and carmustine, cytarabine, etoposide, and melphalan followed by autologous hematopoietic stem cell transplantation in patients with CD20-positive B-cell non-Hodgkin's lymphoma.
• Correlate the effect of changes in levels of sCD20 with clinical outcomes in patients treated with this regimen.
• Determine the response rate in patients treated with this regimen.
• Determine the event-free survival of patients treated with this regimen.
• Determine the toxicity profile of this regimen in these patients.

OUTLINE: Patients receive rituximab IV over approximately 3-4 hours once weekly for 2 weeks followed 1 week later by hematopoietic stem cell or bone marrow harvest.

Patients then receive a third dose of rituximab IV over approximately 3-4 hours on day -7 or -6. Patients also receive high-dose chemotherapy comprising carmustine IV on day -6, cytarabine IV and etoposide IV twice daily on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplantation on day 0.

Patients who have less than a complete remission at day 100 post-transplantation receive 4 additional doses of rituximab IV over approximately 3-4 hours once weekly for 4 weeks.

Patients are followed at day 100, at 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

• Biological: rituximab
• Drug: carmustine
• Drug: cytarabine
• Drug: etoposide
• Drug: melphalan
• Procedure: autologous bone marrow transplantation
• Procedure: peripheral blood stem cell transplantation

DISEASE CHARACTERISTICS:

• Diagnosis of non-Hodgkin's lymphoma

  • Any B cell
• CD20-positive disease
• Failed prior primary induction therapy

• Meets 1 of the following criteria:

  • Chemotherapy-refractory disease
  • Received at least 3 prior chemotherapy regimens
  • Mantle cell lymphoma
• Eligible for transplantation
• No history of T-cell lymphoma

PATIENT CHARACTERISTICS:

Age

• 19 and over

Performance status

• WHO 0-2

Life expectancy

• At least 6 months

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3*
• Platelet count > 50,000/mm^3*
• Hemoglobin > 9.0 g/dL* NOTE: *Unless due to lymphomatous involvement of the bone marrow

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or nursing
• Fertile patients must use 2 methods of effective contraception
• No other concurrent serious disease or condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified