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Combination Bortezomib and Rituximab in Patients With Waldenstrom's Macroglobulinemia (WM)

Primary Purpose

Waldenstrom's Macroglobulinemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bortezomib
Rituximab
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Waldenstrom's Macroglobulinemia focused on measuring relapsed Waldenstrom's macroglobulinemia, refractory Waldenstrom's macroglobulinemia, Velcade, WM

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

bortezomib and rituximab

Arm Description

bortezomib and rituximab

Outcomes

Primary Outcome Measures

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.)
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.)

Secondary Outcome Measures

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.
Duration of Response in Patients With WM
Time from documentation of first response to progressive disease.

Full Information

First Posted
January 12, 2007
Last Updated
October 6, 2020
Sponsor
Dana-Farber Cancer Institute
Collaborators
Millennium Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00422799
Brief Title
Combination Bortezomib and Rituximab in Patients With Waldenstrom's Macroglobulinemia (WM)
Official Title
Phase II Study of Combination Bortezomib (Velcade PS-341) and Rituximab in Patients With Previously Untreated and Relapsed/Refractory Waldenstrom's Macroglobulinemia
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
August 30, 2006 (Actual)
Primary Completion Date
October 9, 2015 (Actual)
Study Completion Date
October 9, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Millennium Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Waldenstrom's Macroglobulinemia
Keywords
relapsed Waldenstrom's macroglobulinemia, refractory Waldenstrom's macroglobulinemia, Velcade, WM

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
bortezomib and rituximab
Arm Type
Experimental
Arm Description
bortezomib and rituximab
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
Once weekly for 3 weeks
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
Intravenously once a week for the first and fourth weeks of a cycle
Primary Outcome Measure Information:
Title
Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia (WM)
Description
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
Title
Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Previously Untreated Waldenstrom's Macroglobulinemia (WM)
Description
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
Secondary Outcome Measure Information:
Title
Time to Progression in Patients With WM
Description
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
Title
Duration of Response in Patients With WM
Description
Time from documentation of first response to progressive disease.
Time Frame
5 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Irene Ghobrial, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20142586
Citation
Ghobrial IM, Hong F, Padmanabhan S, Badros A, Rourke M, Leduc R, Chuma S, Kunsman J, Warren D, Harris B, Sam A, Anderson KC, Richardson PG, Treon SP, Weller E, Matous J. Phase II trial of weekly bortezomib in combination with rituximab in relapsed or relapsed and refractory Waldenstrom macroglobulinemia. J Clin Oncol. 2010 Mar 10;28(8):1422-8. doi: 10.1200/JCO.2009.25.3237. Epub 2010 Feb 8.
Results Reference
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Combination Bortezomib and Rituximab in Patients With Waldenstrom's Macroglobulinemia (WM)

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