Zevalin and Velcade in Relapsed/Refractory Mantle Cell Lymphoma
Primary Purpose
Mantle-Cell Lymphoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rituximab, Bortezomib,Y90 ibritumomab tiuxetan
Sponsored by
About this trial
This is an interventional treatment trial for Mantle-Cell Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Patients with relapsed or refractory Mantle Cell lymphoma with measurable disease.
- Age > 18 years old
- Expected survival >/= 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 at initiation of study (Appendix I).
- Laboratory tests meet the levels specified in the protocol
Exclusion Criteria:
- Patients must not have received chemotherapy, radiation or surgical resection of malignancy within 3 weeks of study initiation. However, if they have received nitrosurea or mitomycin C then they should not be enrolled in the study until 6 weeks after therapy was last received.
- No limitations to number of prior therapies
- No prior radioimmunotherapy (RIT)
- Prior bortezomib is allowed
- Patient must be fully recovered from all toxicities associated with prior surgery, radiation treatment, chemotherapy or immunotherapy.
- No active, serious infection or medical or psychiatric illness likely to interfere with participation in this clinic trial
- No known HIV infection
- No active central nervous system (CNS) involvement
- Bone Marrow Involvement >/= 25% within 30 days of initiation of study treatment
- Pregnant or breast feeding
- No patients who have received Granulocyte colony-stimulating factor (G-CSF) or Granulocyte macrophage colony-stimulating factor (GM-CSF) within the 14 days prior to initiating protocol
- No patient who has had major surgery within the four weeks prior to initiating protocol therapy
- No patients with pleural effusion or significant ascites
Sites / Locations
- Duke University Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Zevalin + Velcade
Arm Description
Drug: Rituximab, Bortezomib,Y90 ibritumomab tiuxetan Other Names: Rituxan Velcade Zevalin Rituximab 250mg/m2 will be given on day 1 and on day 8. Bortezomib 1.5mg/m2 will be given on Days 1, 4, 8, and 11. Y90 ibritumomab tiuxetan will be given on Day 8. Dosage will be based on the platelet count obtained at the time of study enrollment. The dose will be 0.4 millicurie (mCi)/kg unless the enrollee's platelets are between 100,000 and 150,000 in which case a dose of 0.3mCi/Kg will be used. Patients who weigh over 80 Kg will receive a maximum dose of 32mCi.
Outcomes
Primary Outcome Measures
Response Rate (Complete Response + Partial Response)
Disease will be assessed every 3 months.
The Cheson criteria will be used to define response:
Complete Response = Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present prior to therapy.
Partial Response = A decrease of ≥ 50% in the sum of the products of their greatest transverse diameters (SPD) of up to six of the largest dominant nodes or nodal masses. These nodes or masses should be selected according to the following features: a) they should be clearly measurable in at least two perpendicular measurements; b) they should be from as disparate regions of the body as possible; and c) they should include mediastinal and retroperitoneal areas of disease whenever these sites are involved.
Secondary Outcome Measures
Number of Participants With Progression Free Survival
Progression-free survival will be defined as time from on-study to disease progression or death, whichever comes first
Overall Survival at 1 Year
Number of participants who were alive at the 1 year time point. (Overall survival will be defined as the time from on-study to death due to any cause.)
Overall Survival at 5 Year
Number of participants who were alive at the 5 year time point. (Overall survival will be defined as the time from on-study to death due to any cause.)
Full Information
NCT ID
NCT01497275
First Posted
December 20, 2011
Last Updated
June 18, 2015
Sponsor
Duke University
Collaborators
Spectrum Pharmaceuticals, Inc
1. Study Identification
Unique Protocol Identification Number
NCT01497275
Brief Title
Zevalin and Velcade in Relapsed/Refractory Mantle Cell Lymphoma
Official Title
A Phase II Study Evaluating Combined Zevalin(Ibritumomab Tiuxetan)and Velcade(Bortezomib)in Relapsed/Refractory Mantle Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Terminated
Why Stopped
Low accrual due to the approval of new drugs for use in Mantle cell lymphoma.
Study Start Date
February 2012 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Spectrum Pharmaceuticals, Inc
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the effects (good and bad) of the combination of ibritumomab tiuxetan (Zevalin) and bortezomib (Velcade) in patients with relapsed/refractory mantle cell lymphoma.
Zevalin is a monoclonal antibody that is combined with a radioactive substance and given with another monoclonal antibody called rituximab (Rituxan). It works by attaching to cancer cells and releasing radiation to damage those cells. Both Zevalin and Rituxan are given in this study, along with Velcade.
Detailed Description
This is a non-randomized, unblinded single arm Phase II trial to evaluate the combination of yttrium90 ibritumomab tiuxetan and bortezomib in patients with relapsed/refractory mantle cell lymphoma (MCL). Standard hematology and chemistries, imaging and bone marrow biopsies will be done.
Research tests: 17cc of blood will be collected at screen, Day 8 OR 11 and month 3. Samples will be collected and stored for future analysis. These analyses may include but are not limited to measurements of proteasome inhibition. No genetic studies will be performed on these samples. Samples will be destroyed at the end of the study.
Primary Objective Estimate the overall response rate (CR + PR) of the combination of bortezomib and ibritumomab tiuxetan in patients with relapsed/refractory mantle cell lymphoma.
Secondary Objectives
Estimate the progression free and overall survival in patients with relapsed/refractory mantle cell lymphoma who receive bortezomib and ibritumomab tiuxetan.
Assess the toxicity of the combination of bortezomib and ibritumomab tiuxetan in patients with relapsed/refractory MCL.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mantle-Cell Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Zevalin + Velcade
Arm Type
Experimental
Arm Description
Drug: Rituximab, Bortezomib,Y90 ibritumomab tiuxetan
Other Names:
Rituxan Velcade Zevalin
Rituximab 250mg/m2 will be given on day 1 and on day 8. Bortezomib 1.5mg/m2 will be given on Days 1, 4, 8, and 11. Y90 ibritumomab tiuxetan will be given on Day 8. Dosage will be based on the platelet count obtained at the time of study enrollment. The dose will be 0.4 millicurie (mCi)/kg unless the enrollee's platelets are between 100,000 and 150,000 in which case a dose of 0.3mCi/Kg will be used. Patients who weigh over 80 Kg will receive a maximum dose of 32mCi.
Intervention Type
Drug
Intervention Name(s)
Rituximab, Bortezomib,Y90 ibritumomab tiuxetan
Other Intervention Name(s)
Rituxan, Velcade, Zevalin
Intervention Description
Rituximab 250mg/m2 will be given on day 1 and on day 8. Bortezomib 1.5mg/m2 will be given on Days 1, 4, 8, and 11. Y90 ibritumomab tiuxetan will be given on Day 8. Dosage will be based on the platelet count obtained at the time of study enrollment. The dose will be 0.4mCi/kg unless the enrollee's platelets are between 100,000 and 150,000 in which case a dose of 0.3mCi/Kg will be used. Patients who weigh over 80 Kg will receive a maximum dose of 32mCi.
Primary Outcome Measure Information:
Title
Response Rate (Complete Response + Partial Response)
Description
Disease will be assessed every 3 months.
The Cheson criteria will be used to define response:
Complete Response = Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present prior to therapy.
Partial Response = A decrease of ≥ 50% in the sum of the products of their greatest transverse diameters (SPD) of up to six of the largest dominant nodes or nodal masses. These nodes or masses should be selected according to the following features: a) they should be clearly measurable in at least two perpendicular measurements; b) they should be from as disparate regions of the body as possible; and c) they should include mediastinal and retroperitoneal areas of disease whenever these sites are involved.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Number of Participants With Progression Free Survival
Description
Progression-free survival will be defined as time from on-study to disease progression or death, whichever comes first
Time Frame
6 months
Title
Overall Survival at 1 Year
Description
Number of participants who were alive at the 1 year time point. (Overall survival will be defined as the time from on-study to death due to any cause.)
Time Frame
1 year
Title
Overall Survival at 5 Year
Description
Number of participants who were alive at the 5 year time point. (Overall survival will be defined as the time from on-study to death due to any cause.)
Time Frame
5 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with relapsed or refractory Mantle Cell lymphoma with measurable disease.
Age > 18 years old
Expected survival >/= 3 months
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 at initiation of study (Appendix I).
Laboratory tests meet the levels specified in the protocol
Exclusion Criteria:
Patients must not have received chemotherapy, radiation or surgical resection of malignancy within 3 weeks of study initiation. However, if they have received nitrosurea or mitomycin C then they should not be enrolled in the study until 6 weeks after therapy was last received.
No limitations to number of prior therapies
No prior radioimmunotherapy (RIT)
Prior bortezomib is allowed
Patient must be fully recovered from all toxicities associated with prior surgery, radiation treatment, chemotherapy or immunotherapy.
No active, serious infection or medical or psychiatric illness likely to interfere with participation in this clinic trial
No known HIV infection
No active central nervous system (CNS) involvement
Bone Marrow Involvement >/= 25% within 30 days of initiation of study treatment
Pregnant or breast feeding
No patients who have received Granulocyte colony-stimulating factor (G-CSF) or Granulocyte macrophage colony-stimulating factor (GM-CSF) within the 14 days prior to initiating protocol
No patient who has had major surgery within the four weeks prior to initiating protocol therapy
No patients with pleural effusion or significant ascites
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Beaven, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Zevalin and Velcade in Relapsed/Refractory Mantle Cell Lymphoma
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