Bortezomib, Dexamethasone, and Rituximab in Untreated Waldenstroms Macroglobulinemia

NCT00832234 | Completed Phase 2

• 2 other identifiers: EMN-01 (26866138CAN 2021)EudraCT-nr. 2006-003563-31
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II multicenter study designed to evaluate the safety and efficacy of combination BDR. BDR will be administered in one 21-day treatment cycle followed by four 35-day treatment cycles to patients with WM.

Conditions

Waldenstroms Macroglobulinemia

Keywords

Morbus Waldenstrom; Waldenstroms Macroglobulinemia; Therapy; Rituximab; Dexamethasone; Bortezomib

Outcome Measures

Primary Outcomes (1)

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

  Two years

Secondary Outcomes (1)

• Time to progression following treatment with BDR The safety and tolerability of BDR in patients with WM.

  Two years

Study Arms (1)

BDR

EXPERIMENTAL

Drug: Bortezomib, Dexamethasone, Rituximab

Interventions

Bortezomib, Dexamethasone, Rituximab DRUG

The combination of bortezomib, dexamethasone and rituximab will be administered in five treatment cycles. 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 one. 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 375mg/m2 IV will be administered. A total of 8 infusions of rituximab will be administered. The administration of bortezomib before rituximab may abrogate the IgM flare phenomenon that occurs frequently after the first course of rituximab.

Also known as: Velcade, MabThera

BDR

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 Waldenstroms macroglobulinemia as defined by consensus panel one of the Second International Workshop on Waldenstroms macroglobulinemia.
• All patients with the diagnosis of WM will be evaluable for response according to the response criteria
• 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 Waldenstroms Macroglobulinemia.
• 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

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

• European Myeloma Network B.V.: lead
• University of Athens: collaborator
• University of Roma La Sapienza: collaborator
• Niguarda Hospital: collaborator
• University of Turin, Italy: collaborator
• University of Salamanca: collaborator
• Hospital Clinic of Barcelona: collaborator
• Hotel Dieu Hospital: collaborator
• Erasmus Medical Center: collaborator
• University Hospital, Toulouse: collaborator
• Fondazione IRCCS Policlinico San Matteo di Pavia: collaborator
• Laikο General Hospital, Athens: collaborator
• Klinikum der Universitaet Muenchen, Grosshadern: collaborator
• Aalborg University Hospital: collaborator
• Centre Hospitalier de Lens: collaborator
• Universitaire Ziekenhuizen KU Leuven: collaborator
• Theagenio Cancer Hospital: collaborator
• University of Wuerzburg: collaborator
• Skane University Hospital: collaborator
• Sahlgrenska University Hospital: collaborator

Study Sites (1)

University of Athens School of Medicine

Athens, Greece

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

Bortezomib; Dexamethasone; 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; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Meletios A Dimopoulos, MD

  University of Athens School of Medicine, Alexandra Hospital, Athens, Greece

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor Office Director, Professor

Study Record Dates

• First Submitted: January 27, 2009
• First Posted: January 30, 2009
• Study Start: September 1, 2006
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2013
• Last Updated: February 18, 2015

Record last verified: 2015-02

Locations

GR (1)