Phase II Study of VcR-CVAD With Rituximab Consolidation and Maintenance for Untreated Mantle Cell Lymphoma

Study Overview
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Brief Summary
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Patients will receive Rituximab, Bortezomib, cyclophosphamide, Doxorubicin, Vincristine, Dexamethasone in three week intervals for 6 cycles; then rituximab consolidation (weekly x 4) , then one dose of rituximab every 12 weeks until 5 years or disease progression.

Detailed Description
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Primary objective is to estimate the overall response rate (ORR) and the complete response rate (CRR) to the VcR CVAD regimen (response rate at completion of induction). Patients will receive Rituximab, Bortezomib, cyclophosphamide, Doxorubicin, Vincristine, Dexamethasone in three week intervals for 6 cycles; then rituximab consolidation (weekly x 4) , then one dose of rituximab every 12 weeks until 5 years or disease progression.

Official Title
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Phase II Study of VcR-CVAD With Rituximab Consolidation and Maintenance for Untreated Mantle Cell Lymphoma

Conditions
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Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Rituximab
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed CD20+ mantle cell lymphoma, with measurable or evaluable disease, no prior chemotherapy, immunotherapy or radiotherapy except for 1 cycle of CHOP-like chemotherapy. Exclusion Criteria: Patients with known CNS disease, known HIV infection, grade 2 or greater peripheral neuropathy, history of myocardial infarction in last 6 months, or patients who are Hepatitis B Surface Antigen positive.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VCR-CVAD with rituximab maintenance<br>Induction chemotherapy with Bortezomib, cyclophosphamide, rituximab, vincristine, doxorubicin, and dexamethasone. Subjects will receive 6 cycles of induction chemotherapy, of 21 days each. After completing induction, subjects will receive rituximab consolidation (4 weeks), and then rituximab maintenance therapy for up to 5 years. | Drug: Bortezomib<br>* Administered by IV at 1.3 mg/m2 days 1 and 4 of each 21 day cycle.<br>* Other names: Velcade, PS-341;Drug: Rituximab<br>* Administered by IV 375 mg/m2 IV day 1 of each cycle during induction chemotherapy, then weekly for four weeks during consolidation therapy; and then once every 12 weeks for up to 5 years (or until disease progression).<br>* Other names: Rituxan;Drug: Cyclophosphamide<br>* Administered by IV at 300 mg/m2, 6 doses spaced 12 hours apart on days 1-3 of each cycle, to start after completion of rituximab infusion<br>* Other names: cytoxan;Drug: Doxorubicin<br>* Given as a continuous infusion, 50 mg/m2 over 48 hours days 1-2 of each cycle, to start after completion of rituximab infusion.<br>Drug: Vincristine<br>* 1 mg administered by IV on day 3 of each cycle.<br>Drug: Dexamethasone<br>* 40 mg orally on days 1-4 of each cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) at the Completion of Induction Chemotherapy, Which is the Percent of Complete Responses (CR) Plus Percent of Partial Responses (PR). | Patients were considered evaluable for response if they completed at least 2 cycles of therapy and had undergone an initial response evaluation, or had disease progression after 1 cycle of therapy. 1999 International Working Group criteria defines a CR as patients with complete disappearance of disease, or regression of all lymph nodes to 1.5 cm in greatest diameter or less. Partial Response indicates patients responded to treatment with a reduction in the amount of tumor (50 percent or more). Overall response rate is the percent of complete responses plus the percent of partial responses. | At completion of induction therapy (21 weeks) | 
| Complete Response Rate (CR) at the End of Induction Chemotherapy | Complete Response Rate (CRR) as defined by 1999 International Working Group criteria, is defined as patients with complete disappearance of disease, or regression of all lymph nodes to 1.5 cm in greatest diameter or less. All subjects who had completed 2 cycles of therapy and had at least one disease evaluation, or had completed 1 cycle of therapy with progressive disease, were considered evaluable. | at 21 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 Year Progression Free Survival | This is the percent of subjects who had not had any recurrence or relapse of disease as of 3 years after enrollment in the study. | 36 months | 
| 3 Year Overall Survival (OS) | This is the percent of participants who were still alive at 3 years after study entry. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Untreated Mantle Cell Lymphoma