Velcade (Bortezomib, PS-341) and Rituximab in Relapsed/Refractory Mantle Cell and Follicular Non-Hodgkin's Lymphoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Drug: Velcade
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.
Other Names:
Drug: Rituximab
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.]
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ohio State University Medical Center | Columbus | Ohio | United States | 43210 |
Sponsors and Collaborators
- Ohio State University Comprehensive Cancer Center
Investigators
- Principal Investigator: Kristie Blum, MD, The Ohio State University Comprehensive Medical Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- OSU-0430
- NCI-2011-03233
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Velcade and Rituximab |
|---|---|
| Arm/Group Description | 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 |
| Period Title: Overall Study | |
| STARTED | 25 |
| COMPLETED | 25 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Velcade and Rituximab |
|---|---|
| Arm/Group Description | 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 |
| Overall Participants | 25 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
9
36%
|
| >=65 years |
16
64%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
7
28%
|
| Male |
18
72%
|
| Region of Enrollment (participants) [Number] | |
| United States |
25
100%
|
| Lymphoma Disease Stages (participants) [Number] | |
| I(lymph node area or 1 organ outside lymph system |
2
8%
|
| II(2 or more groups of lymph nodes) |
1
4%
|
| Stage III(lymph node areas on both sides) |
9
36%
|
| IV(outside lymph system into organ) |
13
52%
|
| B-symptoms (participants) [Number] | |
| Yes |
6
24%
|
| No |
19
76%
|
| Disease Type (participants) [Number] | |
| Mantle cell lymphoma |
14
56%
|
| Follicular lymphoma |
11
44%
|
Outcome Measures
| Title | Overall Response Rate |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Velcade and Rituximab |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 25 |
| All patients |
40
|
| Patients with follicular lymphoma |
55
|
| Patients with MCL |
29
|
| Title | Assess the Toxicity of Combination Rituximab and Velcade™ in Patients With Previously Treated Mantle Cell and Follicular Lymphoma. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| grade 3 neurotoxicity which consisted of constipation/ileus, sensory or motor neuropathy, or orthostatic hypotension |
| Arm/Group Title | Velcade and Rituximab |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 25 |
| Number [patients] |
13
|
| Title | Progression-free Survival(PFS) |
|---|---|
| Description | To correlate serial plasma rituximab levels with response and progression-free survival. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Velcade and Rituximab |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 25 |
| All patients |
24
|
| Responding patients |
60
|
| Title | Correlative Studies |
|---|---|
| Description | |
| Time Frame | During induction (weeks 1-15); PK every 2 months during maintenance. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data not collected and analyzed |
| Arm/Group Title | Velcade and Rituximab |
|---|---|
| Arm/Group Description | 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: 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. Rituximab: 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. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Velcade and Rituximab | |
| Arm/Group Description | 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 | |
All Cause Mortality |
||
| Velcade and Rituximab | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Velcade and Rituximab | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/25 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Velcade and Rituximab | ||
| Affected / at Risk (%) | # Events | |
| Total | 25/25 (100%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 2/25 (8%) | 2 |
| Febrile neutropenia | 1/25 (4%) | 1 |
| Gastrointestinal disorders | ||
| nausea/vomiting | 1/25 (4%) | 1 |
| Constipation/ileus | 3/25 (12%) | 3 |
| General disorders | ||
| Neutropenia | 3/25 (12%) | 3 |
| Fatigue | 8/25 (32%) | 8 |
| Injury, poisoning and procedural complications | ||
| Thrombocytopenia | 2/25 (8%) | 2 |
| Investigations | ||
| Myositis/Creatinine kinase elevation | 1/25 (4%) | 1 |
| Metabolism and nutrition disorders | ||
| Anorexia | 1/25 (4%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Sensory Neuropathy | 9/25 (36%) | 9 |
| Motor Neuropathy | 1/25 (4%) | 1 |
| Nervous system disorders | ||
| Autonomic neuropathy | 3/25 (12%) | 3 |
| Skin and subcutaneous tissue disorders | ||
| Rash | 1/25 (4%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Kristie Blum, MD |
|---|---|
| Organization | The Ohio State University Comprehensive Cancer Center |
| Phone | 614-293-4519 |
| Kristie.Blum@osumc.edu |
- OSU-0430
- NCI-2011-03233