Combination Bortezomib and Rituximab in Patients With Waldenstrom's Macroglobulinemia

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Waldenstrom's Macroglobulinemia	Drug: Bortezomib; Drug: Rituximab	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	63 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase II Study of Combination Bortezomib (Velcade PS-341) and Rituximab in Patients With Previously Untreated and Relapsed/Refractory Waldenstrom's Macroglobulinemia
Actual Study Start Date :	August 30, 2006
Actual Primary Completion Date :	October 9, 2015
Actual Study Completion Date :	October 9, 2015

Arms and Interventions

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Arm	Intervention/treatment
Experimental: bortezomib and rituximab; bortezomib and rituximab	Drug: Bortezomib; Once weekly for 3 weeks; Other Name: Velcade Drug: Rituximab; Intravenously once a week for the first and fourth weeks of a cycle; Other Name: Rituxan

Outcome Measures

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Primary Outcome Measures :

1. Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Relapsed or Refractory WM. [ Time Frame: 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.)
2. Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Previously Untreated WM [ Time Frame: 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 Outcome Measures :

1. Time to Progression in Patients With WM [ Time Frame: 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.
2. Duration of Response in Patients With WM [ Time Frame: 5 Years ]
   Time from documentation of first response to progressive disease.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Dana-Farber Cancer Institute

Millennium Pharmaceuticals, Inc.

Investigators

Principal Investigator:	Irene Ghobrial, MD	Dana-Farber Cancer Institute

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

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.

Responsible Party:	Irene Ghobrial, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00422799 History of Changes
Other Study ID Numbers:	06-008
First Posted:	January 17, 2007
Results First Posted:	January 26, 2018
Last Update Posted:	January 26, 2018
Last Verified:	December 2017

Keywords provided by Irene Ghobrial, MD, Dana-Farber Cancer Institute:

relapsed Waldenstrom's macroglobulinemia; refractory Waldenstrom's macroglobulinemia; Velcade; WM

Additional relevant MeSH terms:

Waldenstrom Macroglobulinemia; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders	Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Rituximab; Bortezomib; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents