FASE II STUDY WITH BORTEZOMIB, RITUXIMAB AND BENDAMUSTIN –BRB- FOR NON-HODGKIN LYMPHOPLASMACYTIC LYMPHOMA/WALDENSTROM MACROGLOBULINEMIA’S PATIENTS AT FIRST RELAPSE

• Conditions: ON-HODGKIN LYMPHOPLASMACYTIC LYMPHOMA/WALDENSTROM MACROGLOBULINEMIA’S PATIENTS; MedDRA version: 16.1Level: PTClassification code 10047801Term: Waldenstrom's macroglobulinaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-005129-22-IT
• Lead Sponsor: Fondazione Italiana Linfomi

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03-17
• Last Update Posted: 30 June 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

-Histological proven diagnosis of Lymphoplasmacytic/citoid lymphoma/Waldenstrom macroglobulinemia according to REAL/WHO Classification
-Relapsed/refractory disease after receiving one line chemotherapy
-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
-ECOG performance status 0- 2
-LVEF =45% or FS =37%
-Creatinine up to 1.5 x ULN
-Conjugated bilirubin up to 2 x ULN
-Alkaline phosphatase and transaminases up to 2 x ULN
-Written informed content

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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

Exclusion Criteria

-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 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
-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-HBcore 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 investiogational 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.<br>Primary Objective is to assess whether the experimental treatment achieves an absolute increase of PFS rate from 50 to 65% at 18 months with respect to the standard treatment. <br><br>;Secondary Objective: Secondary Objectives are to asses: <br>-Overall Response Rate (ORR) <br>-Overall Survival (OS) <br>-Toxicity ;Primary end point(s): Primary endpoint is the asses progression free survival (PFS).<br>PFS is measured from the beginning of therapy to the date of disease progression, relapse or death from any cause. <br>Patients without any relapse at the end of the follow-up will be censored at their last assessment date.;Timepoint(s) of evaluation of this end point: Minimum follow up time required for all patients will be 2 years.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Overall response rate (ORR): a patient is defined as a responder if he has a complete or very good partial or partial response.<br>Overall survival (OS): measured from the beginning of therapy to the date of death from any cause. Patients alive at the time of the final analysis will be censored at the date of the last contact. <br>Toxicity: severe, life- threatening, fatal (grade 3, 4 and 5) and/or serious adverse events are defined according to Common Terminology Criteria for Adverse Events” (CTCAE);Timepoint(s) of evaluation of this end point: Minimum follow up time required for all patients will be 2 years; 5 years for the toxicity.