Waldenstrom's Macroglobulinemia
Conditions
Keywords
relapsed Waldenstrom's macroglobulinemia, refractory Waldenstrom's macroglobulinemia, Velcade, WM
Brief summary
In this study, we are trying to find out if the combination of these two drugs is effective in treating Waldenstrom's macroglobulinemia (WM). The combination of these two drugs has not been studied for patients with relapsed or refractory macroglobulinemia. The U.S. Food and Drug Administration (FDA) has approved bortezomib for the treatment of multiple myeloma, a cancer that is closely related to Waldenstrom's macroglobulinemia.
Detailed description
* Participants will receive 6 cycles of the study treatment with bortezomib and rituximab. Each cycle is 28 days long (4 weeks). * Participants will receive Rituximab intravenously once a week for the first and fourth cycles only. Participants will receive bortezomib once a week for three weeks on and one week off every cycle, for a total of 6 cycles. * During the rituximab infusion, the participants blood pressure and pulse will be monitored frequently. The rate of infusion may be decreased depending upon the side effects that are experienced. * Blood samples will be collected before the first dose and on follow up with every cycle. Blood counts will also be performed every week. * Routine physical exams will be performed at each evaluation. A PET/CAT scan of the chest, abdomen and pelvis at the end of treatment. This scan is required to assess the response of the participants disease. * In order to learn more on how bortezomib and rituximab affect WM, a bone marrow biopsy will be performed. * We anticipate that participants will complete the active therapy over a period of 6 cycles provided that they are benefiting from therapy and have not had any serious side effects. The participant will be followed every three months for 2 years for office visits and laboratory tests.
Interventions
DRUGBortezomib
Once weekly for 3 weeks
DRUGRituximab
Intravenously once a week for the first and fourth weeks of a cycle
Sponsors
Millennium Pharmaceuticals, Inc.
Dana-Farber Cancer Institute
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
* 18 years of age or older * Patients with previously untreated WM and those who have received prior therapy are eligible * Must have received prior therapy for their WM and have relapsed or refractory WM. * CD20 positive disease based on any previous bone marrow immuno-histochemistry or flow cytometric analysis performed up to 3 months prior to enrollment. * Measurable disease * ECOG Performance Status 0,1, or 2 * Total bilirubin \< 2.0 mg/dl * AST \< 3 x ULN * Life expectancy of greater than 12 weeks
Exclusion criteria
* Uncontrolled infection * Other active malignancies * Cytotoxic chemotherapy less than 3 weeks, or biologic therapy less than 2 weeks, or corticosteroids less than 2 weeks, prior to registration. * Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational * Known to be HIV positive or HEP B positive * Radiation therapy less than 2 weeks prior to registration * Grade 2 or greater peripheral neuropathy * Myocardial infarction within 6 months rior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. * Hypersensitivity to bortezomib, boron, or mannitol * Pregnant or breast feeding women * Other investigational drugs within 14 days of enrollment * Serious medical or psychiatric illness likely to interfere with participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia (WM) | 2 Years | Overall Response Rate= Minor response (\>25%-50% reduction in monoclonal IgM from baseline + Partial Response (\>50-90% reduction in monoclonal IgM from baseline)+ Complete Response (Disappearance of monoclonal protein by immunofixation; no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly (confirmed by CT scan), or signs or symptoms attributable to WM. Reconfirmation of the CR status is required at least 6 weeks apart with a second immunofixation.) |
| Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Previously Untreated Waldenstrom's Macroglobulinemia (WM) | 2 years | Overall Response Rate= Minor response (\>25%-50% reduction in monoclonal IgM from baseline + Partial Response (\>50-90% reduction in monoclonal IgM from baseline)+ Complete Response (Disappearance of monoclonal protein by immunofixation; no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly (confirmed by CT scan), or signs or symptoms attributable to WM. Reconfirmation of the CR status is required at least 6 weeks apart with a second immunofixation.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression in Patients With WM | 5 Years | Time to progresion is the defined as the time from study entry to disease progression (PD) or death. Patients without PD are censored at the date of last disease evaluation. PD is defined as a greater than 25% increase in serum monoclonal IgM electrophoresis confirmed by a second measurement at least 2 weeks apart, or progression of clinically significant findings due to disease or symptoms attributable to WM. |
| Duration of Response in Patients With WM | 5 Years | Time from documentation of first response to progressive disease. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bortezomib and Rituximab bortezomib and rituximab
Bortezomib: Once weekly for 3 weeks
Rituximab: Intravenously once a week for the first and fourth weeks of a cycle | 63 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Bortezomib and Rituximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 27 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants |
| Age, Continuous | 63 years |
| Region of Enrollment United States | 63 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 63 |
| other Total, other adverse events | 63 / 63 |
| serious Total, serious adverse events | 11 / 63 |
Outcome results
Primary
Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Previously Untreated Waldenstrom's Macroglobulinemia (WM)
Overall Response Rate= Minor response (\>25%-50% reduction in monoclonal IgM from baseline + Partial Response (\>50-90% reduction in monoclonal IgM from baseline)+ Complete Response (Disappearance of monoclonal protein by immunofixation; no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly (confirmed by CT scan), or signs or symptoms attributable to WM. Reconfirmation of the CR status is required at least 6 weeks apart with a second immunofixation.)
Time frame: 2 years
Population: Participants who were previously untreated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bortezomib and Rituximab | Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Previously Untreated Waldenstrom's Macroglobulinemia (WM) | 23 Participants |
Primary
Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia (WM)
Overall Response Rate= Minor response (\>25%-50% reduction in monoclonal IgM from baseline + Partial Response (\>50-90% reduction in monoclonal IgM from baseline)+ Complete Response (Disappearance of monoclonal protein by immunofixation; no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly (confirmed by CT scan), or signs or symptoms attributable to WM. Reconfirmation of the CR status is required at least 6 weeks apart with a second immunofixation.)
Time frame: 2 Years
Population: Patients who had received at least one prior line of therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bortezomib and Rituximab | Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia (WM) | 30 Participants |
Secondary
Duration of Response in Patients With WM
Time from documentation of first response to progressive disease.
Time frame: 5 Years
Population: All participants enrolled
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bortezomib and Rituximab | Duration of Response in Patients With WM | 1.4 years |
Secondary
Time to Progression in Patients With WM
Time to progresion is the defined as the time from study entry to disease progression (PD) or death. Patients without PD are censored at the date of last disease evaluation. PD is defined as a greater than 25% increase in serum monoclonal IgM electrophoresis confirmed by a second measurement at least 2 weeks apart, or progression of clinically significant findings due to disease or symptoms attributable to WM.
Time frame: 5 Years
Population: All enrolled participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bortezomib and Rituximab | Time to Progression in Patients With WM | 1.6 years |