S0601 Rituximab, Combination Chemotherapy, and Bortezomib Followed by Bortezomib Alone in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma

OBJECTIVES:

Primary

• Determine the 2-year progression-free survival rate in patients with newly diagnosed mantle cell lymphoma treated with induction therapy comprising rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone, and bortezomib followed by bortezomib maintenance (VM) therapy.

Secondary

• Determine the response rate (complete, complete unconfirmed, and partial responses) in patients treated with this regimen.
• Determine the toxicity of VM in these patients.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive R-CHOP-V induction therapy comprising rituximab IV over ≤ 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin hydrochloride IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1; oral prednisone once daily on days 1-5; and bortezomib IV over 30-90 minutes on days 1 and 4. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable disease or better proceed to bortezomib maintenance therapy.
• Maintenance therapy: Beginning 3 months after completion of R-CHOP-V induction therapy, patients receive bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 3 months for up to 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 4 years and then annually for 3 years.

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

DISEASE CHARACTERISTICS:

• Histologically confirmed mantle cell lymphoma (MCL) meeting the following criteria:

• Stage III-IV or bulky stage II disease
• Confirmation of positivity for the following phenotypes by immunohistochemistry or flow cytometry:

• Cluster of differentiation antigen 19 (CD19) (or CD20)
• Cyclin D1 OR evidence of t(11;14) translocation by cytogenetic analysis or fluorescent in situ hybridization
• Newly diagnosed, previously untreated disease
• Bidimensionally measurable disease by conventional techniques

• No nonmeasurable disease only
• Adequate tumor tissue from original diagnostic specimen available

• Tissue obtained by needle aspiration or cytology not allowed
• No clinical evidence of central nervous system (CNS) involvement by lymphoma
• Co-registration on protocols SWOG-8947 and SWOG-8819 is strongly encouraged

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No peripheral neuropathy ≥ grade 2
• No hypersensitivity to bortezomib, boron, or mannitol
• No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer for which the patient is currently in complete remission, or any other cancer for which the patient has been disease free for the past 5 years
• HIV negative

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, radiotherapy, or antibody therapy for lymphoma
• More than 14 days since prior investigational drugs