Chemotherapy and Rituximab With Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma
Chemotherapy and Rituximab With Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die. Monoclonal antibodies such as rituximab can locate tumor cells and
 either kill them or deliver tumor-killing substances to them without harming normal cells.
 Peripheral 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 chemotherapy and rituximab
 with peripheral stem cell transplantation in treating patients who have mantle cell lymphoma.
OBJECTIVES:

 -  Determine the two-year progression-free survival of patients with mantle cell lymphoma
 treated with intensive chemotherapy and rituximab with autologous peripheral blood stem
 cell (PBSC) transplantation.

 -  Determine the complete and partial response rates of patients treated with this regimen.

 -  Determine the disease-free and overall survival of patients treated with this regimen.

 -  Determine the autologous immune reconstitution in patients treated with this regimen.

 -  Determine the feasibility of this regimen in this patient population.

 -  Determine whether treatment with rituximab during autologous PBSC transplantation
 reduces the amount of contaminating lymphoma in the autologous PBSC product.

 OUTLINE: This is a multicenter study.

 Patients receive induction therapy comprising rituximab IV over 4-6 hours on day 1;
 methotrexate IV over 4 hours on day 2; cyclophosphamide IV over 2 hours, doxorubicin IV, and
 vincristine IV on day 3; and oral prednisone on days 3-7. Patients also receive leucovorin
 calcium IV every 6 hours beginning on day 3 and continuing until blood levels of methotrexate
 are safe. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning on day 4 and
 continuing until blood counts recover.

 Induction therapy repeats every 21-28 days for 2 courses in the absence of disease
 progression or unacceptable toxicity. Rituximab may be omitted during course 1 if circulating
 mantle cells are excessive. Patients may receive a third course if more than 15% persistent
 bone marrow involvement is documented.

 Patients with stable or responding disease begin consolidation therapy 29 days after the
 start of the final course of induction therapy. Patients receive cytarabine IV over 2 hours
 twice daily and etoposide IV over 96 hours on days 1-4. Patients also receive rituximab IV
 over 4-6 hours on days 5 or 6 and 12 or 13 and G-CSF SC beginning on day 14 and continuing
 until leukapheresis is complete. Patients undergo leukapheresis beginning between days 22-25
 and continuing until adequate CD34 cells are collected.

 Beginning 4 weeks after recovery from consolidation therapy, patients receive high-dose
 therapy comprising carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4,
 and cyclophosphamide IV over 2 hours on day -2. Patients undergo autologous peripheral blood
 stem cell (PBSC) transplantation on day 0. Patients receive G-CSF SC beginning on day 6 and
 continuing until blood counts recover.

 After blood counts recover and more than 35 days after autologous PBSC transplantation,
 patients receive rituximab IV over 4-6 hours weekly for 2 weeks.

 Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
 annually for up to 10 years.

 PROJECTED ACCRUAL: At least 45 patients will be accrued for this study within 2 years.
DISEASE CHARACTERISTICS:

 -  Histologically confirmed mantle cell lymphoma

 -  Presenting with at least one of the following:

 -  Coexpression of CD20 (or CD19) and CD5 and a lack of CD23 expression by
 immunophenotyping

 -  Positive for cyclin D1 by immunostaining

 -  Presence of t(11,14) by cytogenetic analysis

 -  Molecular evidence of bcl-1/IgH rearrangement

 -  Stage I-IV disease

 -  Stage III or IV if nodular histology mantle cell lymphoma present

 -  Any stage for other mantle cell histologies

 -  No mantle zone histology

 -  No active CNS disease

 -  No symptomatic meningeal lymphoma

 -  No known CNS parenchymal lymphoma

 -  Lumbar puncture showing mantle cell lymphoma allowed

 -  Bidimensionally measurable disease greater than 1 cm

 -  Nonmeasurable disease includes the following:

 -  Bone lesions

 -  Leptomeningeal disease

 -  Ascites

 -  Pleural/pericardial effusion

 -  Inflammatory breast disease

 -  Lymphangitis cutis/pulmonis

 -  Abdominal masses not confirmed and followed by imaging techniques

 -  Cystic lesions

 -  Lesions in a previously irradiated area

 PATIENT CHARACTERISTICS:

 Age:

 -  18 to 69

 Performance status:

 -  Not specified

 Life expectancy:

 -  Not specified

 Hematopoietic:

 -  Not specified

 Hepatic:

 -  Hepatitis B surface antigen and hepatitis C antibody positive patients must meet all
 of the following criteria:

 -  Bilirubin no greater than 2 times upper limit of normal (ULN)

 -  AST no greater than 3 times ULN

 -  Liver biopsy shows no greater than grade 2 fibrosis and no cirrhosis

 Renal:

 -  Creatinine no greater than 2.0 mg/dL

 Cardiovascular:

 -  LVEF at least 45% by MUGA or echocardiogram

 Other:

 -  No known hypersensitivity to murine products

 -  HIV negative

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  No more than 1 prior dose of rituximab

 Chemotherapy:

 -  No more than 1 prior cycle of chemotherapy

 -  At least 3 weeks since prior chemotherapy

 -  No other concurrent chemotherapeutic agents

 Endocrine therapy:

 -  No chronic use of oral corticosteroids for ongoing medical condition

 -  No concurrent hormonal therapy except for non-lymphoma-related conditions (e.g.,
 insulin for diabetes)

 -  Other concurrent corticosteroids for adrenal failure, diffuse alveolar hemorrhage,
 carmustine pneumonitis, or as an anti-emetic allowed

 Radiotherapy:

 -  No prior radiotherapy for mantle cell lymphoma

 -  Concurrent palliative radiotherapy allowed

 -  Concurrent cranial radiotherapy for asymptomatic meningeal lymphoma allowed

 Surgery:

 -  At least 2 weeks since prior major surgery