Mantle-Cell Lymphoma
Conditions
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.
Interventions
DRUGRituximab, Bortezomib,Y90 ibritumomab tiuxetan
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.
Sponsors
Spectrum Pharmaceuticals, Inc
Duke University
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Complete Response + Partial Response) | 3 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression Free Survival | 6 months | Progression-free survival will be defined as time from on-study to disease progression or death, whichever comes first |
| Overall Survival at 1 Year | 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 | 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.) |
Countries
United States
Participant flow
Recruitment details
Recruitment started April, 2012 and closed to accrual May, 2014. Patients were recruited from the Cellular Therapy clinic at Duke.
Participants by arm
| Arm | Count |
|---|---|
| Zevalin + Velcade Drug: Rituximab, Bortezomib,Y90 ibritumomab tiuxetan 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. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Zevalin + Velcade |
|---|---|
| Age, Customized 18-49 Years | 1 participants |
| Age, Customized 50-59 Years | 1 participants |
| Age, Customized 60-69 Years | 3 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
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.
Time frame: 3 months
Population: Only 3 subjects completed the drug regimen; 1 subject did not complete due to disease progression; 1 did not complete due to adverse event.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zevalin + Velcade | Response Rate (Complete Response + Partial Response) | 0 participants |
Secondary
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
Time frame: 6 months
Population: Only 3 subjects provided evaluable data at the 6 month time point. 2 subjects did not reach this time-point so they were not assessed for progression
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zevalin + Velcade | Number of Participants With Progression Free Survival | 0 participants |
Secondary
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.)
Time frame: 1 year
Population: 1 subject did not reach the one year evaluation because the study was terminated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zevalin + Velcade | Overall Survival at 1 Year | 2 participants |
Secondary
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.)
Time frame: 5 year
Population: No analysis completed due to study being terminated prior to the 5 year time point.