Clinical trial NCT00201877: Velcade (Bortezomib, PS-341) and Rituximab in Relapsed/Refractory Mantle Cell and Follicular Non-Hodgkin's Lymphoma
Official title: A Phase II Study of Velcade (Bortezomib, PS-341) and Rituximab in Relapsed/Refractory Mantle Cell and Follicular Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Hodgkin's Lymphoma
Mantle Cell Lymphoma
Keywords: Relapsed/Refractory
NHL
Follicular
Mantle Cell
non-Hodgkin's lymphoma
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2005-09-20
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate
timeFrame: Every 3 months
measure: Assess the Toxicity of Combination Rituximab and Velcade™ in Patients With Previously Treated Mantle Cell and Follicular Lymphoma.
timeFrame: Day 1 of each cycle
Secondary outcomes:
measure: Progression-free Survival(PFS)
timeFrame: 2 years
measure: Correlative Studies
timeFrame: During induction (weeks 1-15); PK every 2 months during maintenance.
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: The Ohio State University Comprehensive Medical Center
name: Kristie Blum, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baiocchi RA, Alinari L, Lustberg ME, Lin TS, Porcu P, Li X, Johnston JS, Byrd JC, Blum KA. Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma. Cancer. 2011 Jun 1;117(11):2442-51. doi: 10.1002/cncr.25792. Epub 2010 Dec 14.