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

Phase 2

Completed

• Conditions: Non-Hodgkin's Lymphoma; Mantle Cell Lymphoma
• Interventions: Drug: Velcade; Drug: Rituximab

• Registration Number: NCT00201877
• Lead Sponsor: Ohio State University Comprehensive Cancer Center

Brief Summary

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

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.

Study Timeline

• Study Start: 2004-12
• Study First Submitted: 2005-09-12
• Study First Submitted QC: 2005-09-19
• Study First Posted: 2005-09-20
• Primary Completion: 2009-06
• Study Completion: 2012-03
• Results First Submitted: 2013-11-12
• Results First Submitted QC: 2014-04-17
• Results First Posted: 2014-05-20
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-07
• Last Update Posted: 2018-03-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Velcade and Rituximab	Velcade	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
Velcade and Rituximab	Rituximab	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

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	Every 3 months	To determine the overall survival in patients with relapsed or refractory mantle cell and follicular lymphoma following treatment with rituximab and Velcade™.
Assess the Toxicity of Combination Rituximab and Velcade™ in Patients With Previously Treated Mantle Cell and Follicular Lymphoma.	Day 1 of each cycle	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Ohio State University Medical Center; 🇺🇸 Columbus, Ohio, United States