Bortezomib, Dexamethasone, and Rituximab in Previously Untreated Patients With Waldenstrom's Macroglobulinemia

NCT01046006 | Completed Phase 2

• 1 other identifier: 26866138-CAN-2021
• Study Type: interventional
• Target: 59
• Locations: 3 countries
• Sites: 4

Brief Summary

Rituximab is a monoclonal antibody with proven efficacy in WM but responses are slow. Bortezomib has shown significant and rapid activity in WM. Combinations of bortezomib with rituximab nad dexamethasone with rituximab have shown synergistic activity in laboratory studies and clinical trials. This is a Phase II multicenter study designed to evaluate the safety and efficacy of the combination of Bortezomib , Rituximab and dexamethasone (BDR). BDR will be administered in one 21-day treatment cycle followed by four 35-day treatment cycles to patients with WM. Bortezomib will be administered as an iv push over 3 to 5 seconds at a dose of 1.3mg/m2/day on days 1,4,8 and 11 of cycle 1. On cycles 2-5 bortezomib will be given at a dose of 1.6mg/m2/day on days 1,8,15 and 22 of each cycle. Only on cycles 2 and 5, following the administration of Bortezomib, dexamethasone 40mg iv and Rituximab 375 mg/m2 iv will be administered. A total of 8 infusions of rituximab will be administered. Subsequently patients rated as CR, PR, MR or SD will be followed without any treatment until there is evidence of progressive disease.

Conditions

Waldenstrom's Macroglobulinemia

Keywords

lymphoma; Bortezomib; Rituximab

Outcome Measures

Primary Outcomes (1)

• To determine the response rate [the combined complete response (CR) + partial response (PR) + minimal response (MR)] following treatment with BDR in patients with previously untreated WM.

  Overall Response Rates

  Every cycle while on active therapy and thereafter every 3 to 4 months for up to 2 years, or until progression of disease is documented.

Secondary Outcomes (1)

• determine time to progression and assess the safety and tolerability of BDR in patients with WM.

  Every cycle while on active therapy and thereafter every 3 to 4 months for up to 2 years, or until progression of disease is documented.

Study Arms (1)

Bortezomib, Rituximab, Dexamethasone

EXPERIMENTAL

BDR will be administered in one 21-day treatment cycle followed by four 35-day treatment cycles to patients with WM. Bortezomib will be administered as an iv push over 3 to 5 seconds at a dose of 1.3mg/m2/day on days 1,4,8 and 11 of cycle 1. On cycles 2-5 bortezomib will be given at a dose of 1.6mg/m2/day on days 1,8,15 and 22 of each cycle. Only on cycles 2 and 5, following the administration of Bortezomib, dexamethasone 40mg iv and Rituximab 375 mg/m2 iv will be administered. A total of 8 infusions of rituximab will be administered. Subsequently patients rated as CR, PR, MR or SD will be followed without any treatment until there is evidence of progressive disease.

Drug: Bortezomib, Rituximab, Dexamethasone

Interventions

Bortezomib, Rituximab, Dexamethasone DRUG

Bortezomib as an iv push over 3 to 5 seconds at a dose of 1.3mg/m2/day on days 1,4,8 and 11 of cycle 1. On cycles 2-5 bortezomib will be given at a dose of 1.6mg/m2/day on days 1,8,15 and 22 of each 35-day cycle. Dexamethasone IV 40 mg will be given on cycles 2 and 5 on days 1,8,15,22 Rituximab IV will be given on cycles 2 and 5, 375 mg/m2, on days 1,8,15,22 iv

Also known as: BDR

Bortezomib, Rituximab, Dexamethasone

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 as defined by consensus panel one of the Second International Workshop on Waldenstrom's macroglobulinemia.1 All patients with the diagnosis of WM will be evaluable for response according to the response criteria (section 8.1)
• No prior systemic treatment for WM. Prior plasmapheresis to control hyperviscosity, is allowed. In that case baseline monoclonal protein levels for assessment of response will be the levels prior to plasmapheresis, if this is the higher value prior to treatment initiation
• Patients must have at least one of the following indications to initiate treatment as defined by "Consensus Panel Two" recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia41.
• Recurrent fever, night sweats, weight loss, fatigue
• Hyperviscosity
• Lymphadenopathy which is either symptomatic or bulky (≥5cm in maximum diameter)
• Symptomatic hepatomegaly and/or splenomegaly
• Symptomatic organomegaly and/or organ or tissue infiltration
• Peripheral neuropathy due to WM
• Symptomatic cryoglobulinemia
• Cold agglutinin anemia
• Immune hemolytic anemia and/or thrombocytopenia
• Nephropathy related to WM
• Amyloidosis related to WM
• Hemoglobin ≤10g/dL

You may not qualify if:

• Prior systemic treatment with WM (plasmapheresis is allowed)
• Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Patient has hypersensitivity to dexamethasone, bortezomib, boron or mannitol.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Cardiac amyloidosis
• Peripheral neuropathy or neuropathic pain grade 2 or higher as defined by NCI CTCAE version 3
• Women who are pregnant. Women who are breast-feeding and do not consent to discontinue breast-feeding. Women of childbearing age who are not willing to use effective anti-conceptive methods for the duration of the study and 6 months thereafter. Men who do not consent not to father a child during the treatment period and six months thereafter.

Sponsors & Collaborators

• Meletios A. Dimopoulos: lead
• European Myeloma Network B.V.: collaborator

Study Sites (4)

Alexandra Hospital , Department of Clinical Therapeutics

Athens, Attica, 115 28, Greece

Location

Laikon Hospital

Athens, Attica, 11528, Greece

Location

Erasmus Medical Center

Rotterdam, 3015 CE, Netherlands

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Related Links

• European Myeloma Network page for BDR in WM trial

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia; Lymphoma

Interventions

Bortezomib; Rituximab; Dexamethasone

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; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Meletios A Dimopoulos, MD

  University of Athens, School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Clinical Therapeutics

Study Record Dates

• First Submitted: January 8, 2010
• First Posted: January 11, 2010
• Study Start: March 1, 2007
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2015
• Last Updated: April 30, 2021

Record last verified: 2021-04

Locations

NL (1); GR (2); ES (1)