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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
European Myeloma Network
Information provided by (Responsible Party):
Meletios A. Dimopoulos, University of Athens
ClinicalTrials.gov Identifier:
NCT01046006
First received: January 8, 2010
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

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.


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

Study Type: Interventional
Study Design: Endpoint Classification: 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 Waldenstrom's Macroglobulinemia: A Multicenter Trial of the European Myeloma Network

Resource links provided by NLM:


Further study details as provided by University of Athens:

Primary Outcome Measures:
  • 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. [ Time Frame: 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • determine time to progression and assess the safety and tolerability of BDR in patients with WM. [ Time Frame: 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. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 61
Study Start Date: March 2007
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
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

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

Other Names:
  • Bortezomib: Velcade
  • Rituximab: 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:

  • 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.

    1. Recurrent fever, night sweats, weight loss, fatigue
    2. Hyperviscosity
    3. Lymphadenopathy which is either symptomatic or bulky (≥5cm in maximum diameter)
    4. Symptomatic hepatomegaly and/or splenomegaly
    5. Symptomatic organomegaly and/or organ or tissue infiltration
    6. Peripheral neuropathy due to WM
    7. Symptomatic cryoglobulinemia
    8. Cold agglutinin anemia
    9. Immune hemolytic anemia and/or thrombocytopenia
    10. Nephropathy related to WM
    11. Amyloidosis related to WM
    12. Hemoglobin ≤10g/dL
    13. Platelet count <100x109/L
    14. 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 >=60.
  • Life-expectancy >3 months.
  • Baseline platelet count >=50 10^9/L, and absolute neutrophil count >= 0.75 10^9/L.
  • Meet the following pretreatment laboratory criteria at the Screening visit conducted within 28 days of study enrollment:
  • AST (SGOT): >3 times the upper limit of institutional laboratory normal.
  • ALT (SGPT): >3 times the upper limit of institutional laboratory normal.
  • Total Bilirubin: >2 times the upper limit of institutional laboratory normal, unless clearly related to the disease.
  • Calculated or measured creatinine clearance: >=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:

  • 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: NCT01046006

Locations
Greece
Alexandra Hospital , Department of Clinical Therapeutics
Athens, Attica, Greece, 115 28
Laikon Hospital
Athens, Attica, Greece, 11528
Netherlands
Erasmus Medical Center
Rotterdam, Netherlands, 3015 CE
Spain
Hospital Universitario de Salamanca
Salamanca, Spain, 37007
Sponsors and Collaborators
Meletios A. Dimopoulos
European Myeloma Network
Investigators
Principal Investigator: Meletios A Dimopoulos, MD University of Athens, School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Meletios A. Dimopoulos, Professor of Clinical Therapeutics, University of Athens
ClinicalTrials.gov Identifier: NCT01046006     History of Changes
Other Study ID Numbers: 26866138-CAN-2021
Study First Received: January 8, 2010
Last Updated: January 30, 2014
Health Authority: Greece: National Organization of Medicines
Greece: Ethics Committee

Keywords provided by University of Athens:
lymphoma
Bortezomib
Rituximab

Additional relevant MeSH terms:
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Rituximab
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents

ClinicalTrials.gov processed this record on November 20, 2014