Mantle Cell Lymphoma, Non-Hodgkin's Lymphoma
Conditions
Keywords
Relapsed/Refractory, NHL, Follicular, Mantle Cell, non-Hodgkin's lymphoma
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.
Interventions
DRUGVelcade
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.
DRUGRituximab
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.
Sponsors
Ohio State University Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | — |
Countries
United States
Participant flow
Recruitment details
From December 2005 until June 2009, 25 patients aged ≥ 18 years with historically confirmed, grade 1 or 2 mantel cell or follicular NHL according to the World Health Organization classification who relapsed or were refractory after at least 1 previous therapy.
Participants by arm
| Arm | Count |
|---|---|
| Velcade and 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 | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Velcade and Rituximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| B-symptoms No | 19 participants |
| B-symptoms Yes | 6 participants |
| Disease Type Follicular lymphoma | 11 participants |
| Disease Type Mantle cell lymphoma | 14 participants |
| Lymphoma Disease Stages II(2 or more groups of lymph nodes) | 1 participants |
| Lymphoma Disease Stages I(lymph node area or 1 organ outside lymph system | 2 participants |
| Lymphoma Disease Stages IV(outside lymph system into organ) | 13 participants |
| Lymphoma Disease Stages Stage III(lymph node areas on both sides) | 9 participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
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.
Time frame: Day 1 of each cycle
Population: grade 3 neurotoxicity which consisted of constipation/ileus, sensory or motor neuropathy, or orthostatic hypotension
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Velcade and Rituximab | Assess the Toxicity of Combination Rituximab and Velcade™ in Patients With Previously Treated Mantle Cell and Follicular Lymphoma. | 13 patients |
Primary
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™.
Time frame: Every 3 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Velcade and Rituximab | Overall Response Rate | All patients | 40 percentage of patients |
| Velcade and Rituximab | Overall Response Rate | Patients with follicular lymphoma | 55 percentage of patients |
| Velcade and Rituximab | Overall Response Rate | Patients with MCL | 29 percentage of patients |
Secondary
Correlative Studies
Time frame: During induction (weeks 1-15); PK every 2 months during maintenance.
Population: Data not collected and analyzed
Secondary
Progression-free Survival(PFS)
To correlate serial plasma rituximab levels with response and progression-free survival.
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Velcade and Rituximab | Progression-free Survival(PFS) | All patients | 24 percentage of patients |
| Velcade and Rituximab | Progression-free Survival(PFS) | Responding patients | 60 percentage of patients |