Velcade (Bortezomib, PS-341) and Rituximab in Relapsed/Refractory Mantle Cell and Follicular Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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This study will determine the overall response rate and toxicity of rituximab and Velcade in combination in patients with relapsed or refractory mantle cell non-Hodgkin's lymphoma.

Detailed Description
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Rationale: Previous studies testing bortezomib and rituximab separately indicate these agents have some efficacy against mantle cell lymphoma (MCL). Bortezomib is a targeted cancer drug that blocks proteasomes. The proteasome is an enzyme complex existing in all cells that influences proteins controlling cellular processes. By blocking the proteasome, bortezomib disrupts biologic pathways such as those related to the growth and survival of cancer cells. Rituximab is a monoclonal antibody that attaches to a protein called the CD20 antigen that is found almost exclusively on the surface of B-cells with leukemia. Once rituximab attaches to the protein, the immune system activates to kill the malignant B-cells. The current study combines bortezomib and rituximab in patients with relapsed or refractory MCL. Purpose: This study will evaluate the safety and efficacy of bortezomib and rituximab in patients with relapsed or refractory MCL. Blood, molecular, and tumor analysis will be conducted to provide researchers with information about areas such as rituximab resistance, the effects of bortezomib on cells associated with immune function, and protein alterations related to the cellular growth and death of MCL. In addition, the role of maintenance therapy and timing of administration in MCL will be assessed. Treatment: Patients in this study will receive bortezomib and rituximab. Both drugs will be administered through intravenous infusions. There are two treatment periods in this study. The first is considered induction therapy where patients will receive bortezomib and rituximab intermittently over an eighteen week period. Lower dosages of rituximab will be given to patients at the beginning of the study to ensure no severe toxicity occurs. Those patients without disease growth after the eighteen weeks of treatments will continue with maintenance therapy. During this time period, patients will be given bortezomib and rituximab for up to one year and a half. Several tests and exams will be conducted throughout the study to closely monitor patients. Treatments will be discontinued due to disease growth or unacceptable side effects.

Official Title
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A Phase II Study of Velcade (Bortezomib, PS-341) and Rituximab in Relapsed/Refractory Mantle Cell and Follicular Non-Hodgkin's Lymphoma

Conditions
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Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: Velcade
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed mantle cell or follicular lymphoma Relapsed or refractory disease ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, 2 or 3 Exclusion Criteria: Pre-existing sensory or motor peripheral neuropathy No active or untreated CNS (Central Nervous System) lymphoma History of severe, life-threatening hypersensitivity or infusion reactions prior rituximab treatment.

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: Velcade and Rituximab<br>Rituximab 375 mg/m2 IV day 1 of weeks 4, 5, 7, 8, 10, 11, 13, and 14 prior to Velcade™ administration. Velcade™ 1.3 mg/m2 IV days 1 and 4 of weeks 1, 2, 4, 5, 7, 8, 10, 11, 13, and 14 | Drug: Velcade<br>* Induction: 1.3 mg/m2 IV days 1 and 4 of weeks 1, 2, 4, 5, 7, 8, 10, 11, 13 & 14. Maintenance: 1.3 mg/m2 IV day 1 weekly x 2 weeks beginning week 20 and continuing every 6 months until month 23.<br>* Other names: PS-341;Drug: Rituximab<br>* Induction: 375 mg/m2 IV day 1 of weeks 4, 5, 7, 8, 10, 11, 13 and 14 prior to Velcade administration. Maintenance: 375 mg/m2 day 1 weekly x 4 weeks.<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | To determine the overall survival in patients with relapsed or refractory mantle cell and follicular lymphoma following treatment with rituximab and Velcade™. | Every 3 months | 
| Assess the Toxicity of Combination Rituximab and Velcade™ in Patients With Previously Treated Mantle Cell and Follicular Lymphoma. | The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for adverse event reporting. | Day 1 of each cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival(PFS) | To correlate serial plasma rituximab levels with response and progression-free survival. | 2 years | 
| Correlative Studies |  | During induction (weeks 1-15); PK every 2 months during maintenance. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed/Refractory, NHL, Follicular, Mantle Cell, non-Hodgkin's lymphoma