Phase II Study of Combination Bortezomib (VELCADE, PS-341), Dexamethasone, and Rituximab (MabThera) (BDR) in Patients with previously untreated Waldenstrom’s Macroglobulinemia (WM). - protocol BDR

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 90

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.Lympadenopathy 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?109/L, and absolute neutrophil count ? 0.75?109/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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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