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

NCT00250926 | Completed Phase 2 Results DMC

• 1 other identifier: 05-180
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Waldenstrom's Macroglobulinemia

Keywords

bortezomib; dexamethasone; rituximab

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Adverse Events

  This outcome measure was to assess the safety and tolerability of bortezomib, dexamethasone and rituximab in patients with untreated Waldenstroms macroglobulinemia.

  33.2 months

• Response Rate

  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.

  33.2 months

• Time to Best Response

  33.2 months

• Time to Progression

  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).

  42 months

Study Arms (1)

Bortezomib, Dexamethasone, Rituximab

EXPERIMENTAL

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; Drug: Dexamethasone; Drug: Rituximab

Interventions

Bortezomib DRUG

Given intravenously on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles

Also known as: Bortezomib (Velcade)

Bortezomib, Dexamethasone, Rituximab

Dexamethasone DRUG

Given intravenously on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles

Also known as: Dexamethasone (Decadron)

Bortezomib, Dexamethasone, Rituximab

Rituximab DRUG

Given intravenously after bortezomib and dexamethasone on day 11 of a 21-day cycle for 8 cycles

Also known as: Rituximab (Rituxan)

Bortezomib, Dexamethasone, Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Beth Israel Deaconess Medical Center: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Treon SP, Ioakimidis L, Soumerai JD, Patterson CJ, Sheehy P, Nelson M, Willen M, Matous J, Mattern J 2nd, Diener JG, Keogh GP, Myers TJ, Boral A, Birner A, Esseltine DL, Ghobrial IM. Primary therapy of Waldenstrom macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. J Clin Oncol. 2009 Aug 10;27(23):3830-5. doi: 10.1200/JCO.2008.20.4677. Epub 2009 Jun 8.

  PMID: 19506160 RESULT

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

Bortezomib; Dexamethasone; Calcium Dobesilate; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Steven P. Treon MD PhD
• Organization: Dana Farber Cancer Institute

steven_treon@dfci.harvard.edu

617 632 2681

Study Officials

• Steven P. Treon, MD, MA, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 8, 2005
• First Posted: November 9, 2005
• Study Start: October 1, 2005
• Primary Completion: March 1, 2007
• Study Completion: February 1, 2009
• Last Updated: April 8, 2016
• Results First Posted: April 8, 2016

Record last verified: 2016-03

Locations

US (2)