fase ii study with brb for non-hodgkin lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia's

Conditions: Waldenstrom's Macroglobulinemia

Summary: this is a prospective, multicenter phase ii trial designed to determine efficacy and safety of bortezomib plus rituximab plus bendamustine in patients with relapsed/refractory waldenstrom's macroglobulinemia.

the progression free survival (pfs) expected for lymphoplasmacytic/lymphoplasmocytoid lymphoma/waldenstrom macroglobulinemia with the same characteristics indicated into the study and treated with standard rituximab plus chemotherapy may be estimated to be 50% at 18 months. the investigators would consider a positive result to increase 18 months-pfs rate from 50 to 65%.

Eligibility criteria:
inclusion criteria: * histological proven diagnosis of lymphoplasmacytic/cytoid lymphoma/waldenstrom macroglobulinemia according to real/who classification * relapsed/refractory disease after receiving one line chemotherapy (rituximab). if patients received bortezomib or bendamustine and have obtained a partial response lasting at least two years. * age \>= 18 * presence of at least one of the following criteria for the definition of active disease: systemic symptoms or hemoglobin less than 10 g/dl (due to lymphoma) or platelets less than 100 x 109/l (due to lymphoma) or symptomatic splenomegaly or bulky disease (\>7 cm) or hyperviscosity syndrome, peripheral neuropathy up to grade 1 (waldenstrom's disease-related), hemolytic anemia, and immune complex vasculitis * life expectancy \>6 months * eastern cooperative oncology group (ecog) performance status 0-2 * left ventricular ejection fraction (lvef) ≥45% or fs ≥37% * creatinine up to 1.5 x upper limit of normal * conjugated bilirubin up to 2 x upper limit of normal * alkaline phosphatase and transaminases up to 2 x upper limit of normal * written informed content exclusion criteria: * patients who received bortezomib or bendamustine first-line therapy, that or haven't obtained at least partial response nor partial response lasting at least two years. * patients not agreeing to take adequate contraceptive precautions during and for at least 6 months after cessation of therapy * history of other malignancies within 3 years prior to study entry except for: adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage, localized prostate cancer treated surgically with curative intent; good prognosis ductal carcinoma in situ (dcis) of the breast treated with lumpectomy alone with curative intent * medical condition requiring long term use (\>1 months) of systemic corticosteroids * active bacterial, viral, or fungal infection requiring systemic therapy * peripheral neuropathy of any grade ≥ 2 \[see appendix section a\] * concurrent medical condition which might exclude administration of therapy * cardiac insufficiency (nyha grade iii/iv) * myocardial infarction within 6 months of entry on study * severe chronic obstructive pulmonary disease with hypoxemia * severe diabetes mellitus difficult to control with adequate insulin therapy * hypertension that is difficult to control * impaired renal function with creatinine clearance \<30 ml/min * hiv positivity hbv positivity with the exception of patients hbsag and hbv-dna negative and ab anti-hb core positive (these patients need to receive prophylaxis with lamivudine) * hcv positivity with the exception of patients with hcv rna negative * participation at the same time in another study in with investigational drugs are used * known hypersensitivity or anaphylactic reactions to murine antibodies or proteins * any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent. * women in pregnancy or breastfeeding