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

Registration Number
NCT00376961
Lead Sponsor
SWOG Cancer Research Network
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
68
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
R-CHOP + Velcadevincristine sulfate6 21-day cycles of standard R-CHOP with 1.3 mg/m\^2 Bortezomib given on days 1 and 4 of each cycle. This is followed by 8 3-month cycles of maintenance with 1.3 mg/m\^2 Bortezomib on days 1, 4, 8 and 11 of each cycle.
R-CHOP + Velcaderituximab6 21-day cycles of standard R-CHOP with 1.3 mg/m\^2 Bortezomib given on days 1 and 4 of each cycle. This is followed by 8 3-month cycles of maintenance with 1.3 mg/m\^2 Bortezomib on days 1, 4, 8 and 11 of each cycle.
R-CHOP + Velcadebortezomib6 21-day cycles of standard R-CHOP with 1.3 mg/m\^2 Bortezomib given on days 1 and 4 of each cycle. This is followed by 8 3-month cycles of maintenance with 1.3 mg/m\^2 Bortezomib on days 1, 4, 8 and 11 of each cycle.
R-CHOP + Velcadecyclophosphamide6 21-day cycles of standard R-CHOP with 1.3 mg/m\^2 Bortezomib given on days 1 and 4 of each cycle. This is followed by 8 3-month cycles of maintenance with 1.3 mg/m\^2 Bortezomib on days 1, 4, 8 and 11 of each cycle.
R-CHOP + Velcadedoxorubicin hydrochloride6 21-day cycles of standard R-CHOP with 1.3 mg/m\^2 Bortezomib given on days 1 and 4 of each cycle. This is followed by 8 3-month cycles of maintenance with 1.3 mg/m\^2 Bortezomib on days 1, 4, 8 and 11 of each cycle.
R-CHOP + Velcadeprednisone6 21-day cycles of standard R-CHOP with 1.3 mg/m\^2 Bortezomib given on days 1 and 4 of each cycle. This is followed by 8 3-month cycles of maintenance with 1.3 mg/m\^2 Bortezomib on days 1, 4, 8 and 11 of each cycle.
Primary Outcome Measures
NameTimeMethod
2-year Progression-free Survival in Patients Treated With Rituximab-CHOP-bortezomib Induction Therapy (RCHOP-V) Followed by Bortezomib Maintenance Therapy (VM)0-2 years

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

Secondary Outcome Measures
NameTimeMethod
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugAssessed 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.

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.

Response Rate in Patients Treated With Rituximab-CHOPbortezomib Induction Therapy (R-CHOP-V) Followed by Bortezomib Maintenance Therapy(VM).At the time of restaging (between Cycles 6 and 7), every 6 months during Cycles 7-14, and at the end of protocol treatment

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.

2-year Overall Survival in Patients Treated With Rituximab-CHOP-bortezomib Induction Therapy (RCHOP-V) Followed by Bortezomib Maintenance Therapy (VM)0-2 years

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

Trial Locations

Locations (146)

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

North Bay Cancer Center

🇺🇸

Fairfield, California, United States

Poudre Valley Hospital

🇺🇸

Fort Collins, Colorado, United States

Broward General Medical Center Cancer Center

🇺🇸

Fort Lauderdale, Florida, United States

M.D. Anderson Cancer Center at Orlando

🇺🇸

Orlando, Florida, United States

Mountain States Tumor Institute at St. Luke's Regional Medical Center

🇺🇸

Boise, Idaho, United States

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Alaska Regional Hospital Cancer Center
🇺🇸Anchorage, Alaska, United States

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