Fase II Study With BRB for Non-Hodgkin Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia’s

Brief Title

Fase II Study With BRB for Non-Hodgkin Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia's

Official Title

Fase II Study With Bortezomib, Rituximab and Bendamustin-BRB- for Non-Hodgkin Lymphoplasmocytic Lymphoma/Waldenstrom Macroglobulinemia's Patients at First Relapse

Brief 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.
    

Detailed Description

      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%.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Progression Free Survival (PFS)

Secondary Outcome

 Overall Response Rate (ORR)

Condition

Waldenstrom's Macroglobulinemia

Intervention

Bortezomib-Rituximab-Bendamustine

Study Arms / Comparison Groups

 Bortezomib-Rituximab-Bendamustine

Description:  Bortezomib-Rituximab-Bendamustine (BRB) combination in patients with relapsed/refractory lymphoplasmocytic/lymphoplasmocytoid lymphoma/Waldenstrom macroglobulinemia after one line of therapy.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

38

Start Date

June 2014

Completion Date

July 22, 2020

Primary Completion Date

November 2017

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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Lorella Orsucci, MD, , 

Location Countries

Italy

Location Countries

Italy

NCT ID

NCT02371148

Organization ID

FIL_BRB

Responsible Party

Sponsor

Study Sponsor

Fondazione Italiana Linfomi ONLUS

Study Sponsor

Lorella Orsucci, MD, Principal Investigator, SC EMATOLOGIA - AO CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO

Verification Date

November 2020