Waldenstroms Macroglobulinemia Clinical Trial
— BDR-WMOfficial 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
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.
| Status | Completed |
| Enrollment | 59 |
| Est. completion date | June 2013 |
| Est. primary completion date | June 2010 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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. |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Greece | University of Athens School of Medicine | Athens |
| Lead Sponsor | Collaborator |
|---|---|
| European Myeloma Network | Aalborg Universitetshospital, Centre Hospitalier de Lens, Erasmus Medical Center, Hospital Clinic of Barcelona, Hotel Dieu Hospital, IRCCS Policlinico S. Matteo, Klinikum der Universitaet Muenchen, Grosshadern, Laikon General District Hospital, Athens, Niguarda Hospital, Sahlgren´s University Hospital, Skane University Hospital, Theagenio Cancer Hospital, Universitaire Ziekenhuizen Leuven, University Hospital, Toulouse, University of Athens, University of Roma La Sapienza, University of Salamanca, University of Turin, Italy, University of Wuerzburg |
Greece,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Yes | |
| Secondary | Time to progression following treatment with BDR The safety and tolerability of BDR in patients with WM. | Two years | Yes |