Combination Bortezomib and Rituximab in Patients With Waldenstrom's Macroglobulinemia

Tracking Information
First Submitted Date ICMJE	January 12, 2007
First Posted Date ICMJE	January 17, 2007
Results First Submitted Date	December 27, 2017
Results First Posted Date	January 26, 2018
Last Update Posted Date	January 26, 2018
Actual Study Start Date ICMJE	August 30, 2006
Actual Primary Completion Date	October 9, 2015 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 27, 2017)	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.); 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.)
Original Primary Outcome Measures ICMJE; (submitted: January 12, 2007)	Assess the response rate of bortezomib and rituximab (VR) in patients with relapsed or refractory WM.
Change History	Complete list of historical versions of study NCT00422799 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 27, 2017)	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.; Duration of Response in Patients With WM [ Time Frame: 5 Years ]Time from documentation of first response to progressive disease.
Original Secondary Outcome Measures ICMJE; (submitted: January 12, 2007)	Evaluate the toxicity of VR in patients with WM; evaluate the time to progression in patients with WM; Study the effect of bortezomib and rituximab on tumor cells in this patient population.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Combination Bortezomib and Rituximab in Patients With Waldenstrom's Macroglobulinemia
Official Title ICMJE	Phase II Study of Combination Bortezomib (Velcade PS-341) and Rituximab in Patients With Previously Untreated and Relapsed/Refractory Waldenstrom's Macroglobulinemia
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.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Waldenstrom's Macroglobulinemia
Intervention ICMJE	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
Study Arms	Experimental: bortezomib and rituximab; bortezomib and rituximab; Interventions: Drug: Bortezomib; Drug: Rituximab
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: December 27, 2017)	63
Original Enrollment ICMJE; (submitted: January 12, 2007)	45
Actual Study Completion Date	October 9, 2015
Actual Primary Completion Date	October 9, 2015 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00422799
Other Study ID Numbers ICMJE	06-008
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Irene Ghobrial, MD, Dana-Farber Cancer Institute
Study Sponsor ICMJE	Dana-Farber Cancer Institute
Collaborators ICMJE	Millennium Pharmaceuticals, Inc.
Investigators ICMJE	Principal Investigator: Irene Ghobrial, MD Dana-Farber Cancer Institute
PRS Account	Dana-Farber Cancer Institute
Verification Date	December 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP