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Study of the Combination of Bortezomib, Dexamethasone, and Rituximab in Patients With Waldenstroms Macroglobulinemia

This study has been completed.
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00250926
First received: November 8, 2005
Last updated: March 10, 2016
Last verified: March 2016
  Purpose
The purpose of this study is to find out if the combination of bortezomib (Velcade), dexamethasone (Decadron) and rituximab (Rituxan) is effective in treating Waldenstrom's macroglobulinemia.

Condition Intervention Phase
Waldenstrom's Macroglobulinemia
Drug: Bortezomib
Drug: Dexamethasone
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of the Combination Bortezomib (Velcade, PS-341), Dexamethasone, and Rituximab in Patients With Waldenstroms Macroglobulinemia

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: 33.2 months ] [ Designated as safety issue: Yes ]
    This outcome measure was to assess the safety and tolerability of bortezomib, dexamethasone and rituximab in patients with untreated Waldenstroms macroglobulinemia.

  • Response Rate [ Time Frame: 33.2 months ] [ Designated as safety issue: No ]

    This outcome measure was to determine the response rate along with attainment of stable disease and time to disease progression following treatment with this patient population. The response rates were defined as follows.

    A complete response (CR) was defined as having resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, absence of bone marrow disease by bone marrow biopsy and aspiration, and resolution of any adenopathy or splenomegaly. A near complete response (nCR) was defined as fulfilling all CR criteria in the presence of a positive immunofixation study. Patients with very good partial response (VGPR), partial response (PR), and minor response (MR) were defined as having a ≥ 90%, ≥ 50%, and 25% to 49% reduction in serum IgM levels, respectively. Progressive disease (PD) occurred when a more than 25% increase in serum IgM level or progression of clinically significant disease parameters was observed.


  • Time to Best Response [ Time Frame: 33.2 months ] [ Designated as safety issue: No ]
  • Time to Progression [ Time Frame: 42 months ] [ Designated as safety issue: No ]
    Progressive Disease (PD) will be defined as a greater than 25% increase in serum IgM monoclonal protein levels from the lowest attained response value as determined by serum electrophoresis, confirmed by at least one other investigation, or progression of clinically significant disease related symptom(s).


Enrollment: 23
Study Start Date: October 2005
Study Completion Date: February 2009
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib, Dexamethasone, Rituximab
A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy.
Drug: Bortezomib
Given intravenously on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles
Other Name: Bortezomib (Velcade)
Drug: Dexamethasone
Given intravenously on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles
Other Name: Dexamethasone (Decadron)
Drug: Rituximab
Given intravenously after bortezomib and dexamethasone on day 11 of a 21-day cycle for 8 cycles
Other Name: Rituximab (Rituxan)

Detailed Description:
  • This is an open-label study which means both the patient and the doctor will know what drugs and doses the patient is receiving throughout the study.
  • Patients will receive 8 cycles of study treatment with bortezomib, dexamethasone and rituximab. Each cycle is 21 days long. Therapy is given on the first, fourth, eighth and eleventh day of each cycle, followed by a 10 day rest period. The first 4 cycles will be given one after the other. Three months after completing the fourth cycle of therapy, patients will receive one cycle of therapy every three months for a total of four more cycles.
  • On the first, fourth, eighth and eleventh day of each cycle, the patient will receive bortezomib and dexamethasone as an intravenous injection through a needle in your vein. On the eleventh day only, the patient will also receive rituximab as an intravenous infusion after getting bortezomib and dexamethasone.
  • Prior to each infusion of rituximab therapy, the patient will be asked to take some medications to prevent or reduce side effects of rituximab. These medications are benadryl, tylenol, and possibly more steroids. The doctor will determine which of these drugs are appropriate for the individual patient.
  • During the rituximab infusion, the patients blood pressure and pulse will be monitored frequently and the infusion rate may be decreased depending upon the side effects experienced.
  • After therapy is completed, the patient will be followed every three months for 2 more years for office visits and laboratory tests to determine how well they are doing and if the therapy continues to benefit them.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinicopathological diagnosis of Waldenstrom's macroglobulinemia (WM)
  • No previous therapy for WM
  • Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level of greater than or equal to 2 times the upper limit of each institution's normal value
  • CD20 positive disease based on any previous bone marrow immuno-histochemistry or flow cytometric analysis performed up to 3 months prior to enrollment
  • Karnofsky performance status > 60
  • Life expectancy > 3 months
  • AST (SGOT) < 3 x ULN
  • ALT (SGPT) < 3 x ULN
  • Total bilirubin < 2 x ULN
  • Calculated or measured creatinine clearance > 30mL/minute
  • Serum sodium > 130 mmol/L
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control
  • Male subject agrees to use an acceptable method for contraception for the duration of the study

Exclusion Criteria:

  • Previous therapy for Waldenstrom's macroglobulinemia
  • Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association 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 dexamethasone, boron or mannitol
  • Pregnant or breast-feeding women
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00250926

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Steven P. Treon, MD, MA, PhD Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: Steven P. Treon, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00250926     History of Changes
Other Study ID Numbers: 05-180 
Study First Received: November 8, 2005
Results First Received: December 19, 2012
Last Updated: March 10, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
bortezomib
dexamethasone
rituximab

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
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Rituximab
Bortezomib
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 23, 2016