Bortezomib, Dexamethasone, and Rituximab in Untreated Waldenstroms Macroglobulinemia (BDR-WM)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2010 by European Myeloma Network.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
University of Athens
University of Roma La Sapienza
Niguarda Hospital
University of Turin, Italy
University of Salamanca
Hospital Clinic of Barcelona
Hotel Dieu Hospital
Erasmus Medical Center
University Hospital, Toulouse
IRCCS Policlinico S. Matteo
Laikon General District Hospital, Athens
Klinikum der Universitaet Muenchen, Grosshadern
Aalborg Universityhospital
Centre hospitalier Dr Schaffner de Lens, France
Universitaire Ziekenhuizen Leuven
Theagenio Cancer Hospital
University of Wuerzburg
Skane University Hospital
Sahlgren´s University Hospital
Information provided by:
European Myeloma Network
ClinicalTrials.gov Identifier:
NCT00832234
First received: January 27, 2009
Last updated: February 24, 2011
Last verified: April 2010
  Purpose

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.


Condition Intervention Phase
Waldenstroms Macroglobulinemia
Drug: Bortezomib, Dexamethasone, Rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Combination Bortezomib, Dexamethasone, and Rituximab in Previously Untreated Patients With Waldenstroms Macroglobulinemia: A Multicenter Trial of the European Myeloma Network

Resource links provided by NLM:


Further study details as provided by European Myeloma Network:

Primary Outcome Measures:
  • The response rate [the combined complete response (CR) + partial response (PR) + minimal response (MR)] following treatment with BDR in patients with previously untreated WM. [ Time Frame: Two years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to progression following treatment with BDR The safety and tolerability of BDR in patients with WM. [ Time Frame: Two years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 61
Study Start Date: September 2006
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BDR Drug: Bortezomib, Dexamethasone, Rituximab
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.
Other Names:
  • Velcade
  • MabThera

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria to be enrolled in this study:

  • 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
  • Amyloidosis related to WM
  • Hemoglobin < 10g/dL
  • Platelet count < 100x109/L
  • Serum monoclonal protein >5g/dL even with no symptoms
  • CD20 positive disease based on any previous bone marrow immunohistochemistry or flow cytometric analysis performed up to 3 months prior to enrollment.
  • Karnofsky performance status more than 60.
  • Life-expectancy >3 months.
  • Baseline platelet count more than 50x109/L, and absolute neutrophil count more than 0.75x109/L.
  • Meet the following pretreatment laboratory criteria at the Screening visit conducted within 28 days of study enrollment:

    • AST (SGOT): less than 3 times the upper limit of institutional laboratory normal.
    • ALT (SGPT): less than 3 times the upper limit of institutional laboratory normal.
  • Total Bilirubin: less than 2 times the upper limit of institutional laboratory normal, unless clearly related to the disease.
  • Calculated or measured creatinine clearance: less than 30 mL/minute. Serum sodium >130 mmol/L.
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

  • Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
  • 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.
  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: NCT00832234

Locations
Greece
University of Athens School of Medicine
Athens, Greece
Sponsors and Collaborators
European Myeloma Network
University of Athens
University of Roma La Sapienza
Niguarda Hospital
University of Turin, Italy
University of Salamanca
Hospital Clinic of Barcelona
Hotel Dieu Hospital
Erasmus Medical Center
University Hospital, Toulouse
IRCCS Policlinico S. Matteo
Laikon General District Hospital, Athens
Klinikum der Universitaet Muenchen, Grosshadern
Aalborg Universityhospital
Centre hospitalier Dr Schaffner de Lens, France
Universitaire Ziekenhuizen Leuven
Theagenio Cancer Hospital
University of Wuerzburg
Skane University Hospital
Sahlgren´s University Hospital
Investigators
Principal Investigator: Meletios A Dimopoulos, MD University of Athens School of Medicine, Alexandra Hospital, Athens, Greece
  More Information

No publications provided

Responsible Party: EMN Secretary Hans E Johnsen, European Myeloma Network
ClinicalTrials.gov Identifier: NCT00832234     History of Changes
Other Study ID Numbers: EMN-01 (26866138CAN 2021), EudraCT-nr. 2006-003563-31
Study First Received: January 27, 2009
Last Updated: February 24, 2011
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: The Danish National Committee on Biomedical Research Ethics
Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency

Keywords provided by European Myeloma Network:
Morbus Waldenstrom
Waldenstroms Macroglobulinemia
Therapy
Rituximab
Dexamethasone
Bortezomib

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
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 31, 2014