Cyclophosphamide W/or W/Out Rituximab and Peripheral Stem Cell Transplantation in Patients With Recurrent Non-Hodgkin's Lymphoma

OBJECTIVES:

• Compare the effects of mobilization therapy with or without rituximab on hematopoietic stem cells, B and T lymphocytes, and natural killer cells in patients with advanced or recurrent B-cell non-Hodgkin's lymphoma.
• Compare the effects of B-lymphocyte purging using concurrent rituximab and mobilization therapy vs a CD34+ cell enrichment device on hematopoietic stem cells, B and T lymphocytes, and natural killer cells in the peripheral blood stem cell (PBSC) infusates.
• Compare the effect of these purging regimens on tumor cell content of PBSC infusates.
• Compare the effects of these regimens on myeloid and lymphoid engraftment after high-dose chemotherapy and autologous PBSC infusion in these patients.
• Compare post-transplantation infection complications in patients treated with these regimens.
• Compare the response and relapse-free survival of patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive mobilization therapy comprising rituximab IV over 2-5 hours on days 1, 8, and 15 and cyclophosphamide IV over 3-6 hours on day 16. Beginning 36-48 hours after the completion of cyclophosphamide, patients receive filgrastim (G-CSF) subcutaneously (SC) daily until blood counts recover. Patients then undergo peripheral blood stem cell (PBSC) collection.

After completion of PBSC collection, patients receive high-dose chemotherapy comprising carmustine IV on days -7 to -3 and etoposide IV and cisplatin IV for 3 days during days -7 to -3. Patients may undergo involved-field radiotherapy to active or previously bulky (more than 5 cm) tumors daily for 7-10 days.

Patients receive unmanipulated PBSCs on day 0. Patients receive G-CSF SC daily beginning 4 hours after completion of PBSC infusion and continuing until neutrophil engraftment.

• Arm II: Patients receive mobilization therapy comprising cyclophosphamide and G-CSF and high-dose chemotherapy comprising carmustine, etoposide, and cisplatin as in arm I. Patients may also undergo involved-field radiotherapy as in arm I. Patients receive CD34 cell-enriched PBSC on day 0 followed by G-CSF as in arm I.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed B-cell non-Hodgkin's lymphoma (NHL)

• Indolent or aggressive histology
• No small lymphocytic lymphoma, Burkitt's lymphoma, or small lymphocytic non-Burkitt's lymphoma
• CD20-positive and/or CD19-positive by immunohistochemistry or flow cytometry
• Second or greater remission allowed

• Partial remission, relapse, or refractory disease must have measurable tumor
• Eligible for high-dose therapy followed by autologous peripheral blood stem cell transplantation
• No CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

Age:

• 12 to 65

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,200/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 2.0 mg/dL

Renal:

• Creatinine clearance at least 60 mL/min
• No renal dysfunction

Cardiovascular:

• LVEF at least 40%
• No cardiac dysfunction
• No myocardial infarction within the past 3 months

Pulmonary:

• FEV_1 greater than 60%
• DLCO at least 60% of predicted
• No pulmonary dysfunction
• No asthma

Other:

• HIV negative
• No significant organ dysfunction
• No severe comorbid condition
• No uncontrolled diabetes
• No severe or active infection
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Chemotherapy
• No prior immunotherapy

Chemotherapy:

• No prior high-dose chemotherapy with or without peripheral blood stem cell transplantation
• No more than 3 prior chemotherapy regimens for NHL
• At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• Prior radiotherapy allowed

Surgery:

• Not specified