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

SWOG Cancer Research Network68 enrolled

Overview

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving rituximab together with combination chemotherapy and bortezomib may kill more cancer cells. Giving bortezomib as maintenance therapy may keep the cancer from progressing. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy and bortezomib followed by bortezomib alone works 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.

Study Type

INTERVENTIONAL

Allocation

Interventions

rituximabBIOLOGICAL

375 mg/m\^2 on day 1 for cycles 1-6.

bortezomibDRUG

1.3 mg/m\^2 on days 1, 4 of cycles 1-6 and on days 1, 4, 8, 11 of cycles 7-14.

cyclophosphamideDRUG

750 mg/m\^2 on day 1 of cycles 1-6.

doxorubicin hydrochlorideDRUG

50 mg/m\^2 on day 1 of cycles 1-6.

prednisoneDRUG

100 mg on days 1-5 of cycles 1-6.

vincristine sulfateDRUG

1.4 mg/m\^2 on day 1 of cycles 1-6.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 120 Years

Medical Language ↔ Plain English

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

Locations (147)

Alaska Regional Hospital Cancer Center

Anchorage, Alaska, United States

Providence Cancer Center

Anchorage, Alaska, United States

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Providence Saint Joseph Medical Center - Burbank

Burbank, California, United States

Outcomes

Primary Outcomes

2-year Progression-free Survival in Patients Treated With Rituximab-CHOP-bortezomib Induction Therapy (RCHOP-V) Followed by Bortezomib Maintenance Therapy (VM)

Measured from date of registration to date of first observation of relapsed or progressive disease, or death due to any cause.

Time frame: 0-2 years

Secondary Outcomes

Response Rate in Patients Treated With Rituximab-CHOPbortezomib Induction Therapy (R-CHOP-V) Followed by Bortezomib Maintenance Therapy(VM).

Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.

Time frame: At the time of restaging (between Cycles 6 and 7), every 6 months during Cycles 7-14, and at the end of protocol treatment

2-year Overall Survival in Patients Treated With Rituximab-CHOP-bortezomib Induction Therapy (RCHOP-V) Followed by Bortezomib Maintenance Therapy (VM)

Measured from date of registration to date of death due to any cause or last contact

Time frame: 0-2 years

Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug

Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

Time frame: Assessed prior to each cycle (for Cycles 2-6), at restaging (between Cycle 6 and 7), every 3 months ( for Cycle 7-14), and at the end of protocol treatment.