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

December 1, 2020 updated by: Fondazione Italiana Linfomi ONLUS

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

38

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Alessandria, Italy, 15121
        • A.O. SS. Antonio e Biagio e C. Arrigo
      • Ancona, Italy, 60126
        • A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
      • Aviano (PN), Italy
        • Centro di riferimento Oncologico - Oncologia Medica A
      • Biella, Italy, 13900
        • A.O. Ospedale Degli Infermi
      • Cagliari, Italy
        • Ospedale Businco, Divisione di Ematologia
      • Meldola (FC), Italy
        • Area Vasta Romagna e IRST
      • Milano, Italy, 20122
        • IRCCS Ospedale Maggiore Policlinico di Milano
      • Modena, Italy, 41124
        • A.O. Universitaria Policlinico Di Modena
      • Novara, Italy, 28100
        • Ospedale Maggiore Della Carita' - Scdu Ematologia
      • Oristano, Italy, 09170
        • Ospedale San Martino, Asl Oristano- Ematologia
      • Pavia, Italy, 27100
        • Ematologia Policlinico San Matteo
      • Piacenza, Italy, 29121
        • AUSL di Piacenza
      • Rimini, Italy, 47924
        • Ausl Di Rimini
      • Torino, Italy, 10126
        • Ematologia 1 - A.O. Citta' Della Salute E Della Scienza Di Torino
      • Torino, Italy
        • Città della Salute e della Scienza SC Ematologia
      • Varese, Italy, 21100
        • Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI
    • ME
      • Messina, ME, Italy, 98158
        • AO Riuniti Papardo Piemonte
    • PZ
      • Rionero in Vulture, PZ, Italy, 85028
        • Centro di Riferimento Oncologico della Basilicata
    • RA
      • Ravenna, RA, Italy, 48100
        • AUSL di Ravenna
    • RC
      • Reggio Calabria, RC, Italy, 89125
        • A.O. Bianchi - Melacrino - Morelli
    • RM
      • Roma, RM, Italy, 00153
        • Nuovo Regina Margherita
    • Salerno
      • Pagani, Salerno, Italy, 84016
        • Uo Oncoematologia, Po "A.Tortora"
    • Treviso
      • Castelfranco Veneto, Treviso, Italy, 31033
        • Ospedale S. Giacomo di Castelfranco Veneto

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bortezomib-Rituximab-Bendamustine
Bortezomib-Rituximab-Bendamustine (BRB) combination in patients with relapsed/refractory lymphoplasmocytic/lymphoplasmocytoid lymphoma/Waldenstrom macroglobulinemia after one line of therapy.
Drug: Bortezomib-Rituximab-Bendamustine

Bortezomib-Rituximab-Bendamustine Bortezomib: 1.3 mg/mq sc days 1, 8, 15, 22* Rituximab: 375 mg/sqm i.v. day 1** Bendamustine: 90 mg/sqm iv days 1-2 or days 2-3 according to institutional/physician choice Repeat cycles every 28 days for a total of 6 cycles *In case of toxicity is omitted

**In cycles 1, in order to avoid tumor lysis syndrome, Rituximab will be given on day 8

Other Names:
  • BRB

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: 18 months

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. 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. PFS is measured from the beginning of therapy to the date of disease progression, relapse or death from any cause.

Patients without any relapse at the end of the follow-up will be censored at their last assessment date.
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: 2 years
Overall response rate (ORR): a patient is defined as a responder if he has a complete or very good partial or partial response, evaluated in based on Waldenstrom macroglobulinemia consensus recommendations of the 6th International Workshop on Waldestrom's macroglobulinemia.
2 years
Overall Survival (OS)
Time Frame: 2 years
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. Minimum follow up time required for all patients will be 2 years.
2 years
Toxicity
Time Frame: 2 years
Toxicity: severe, life- threatening, fatal (grade 3, 4 and 5)
2 years
Number of serious adverse events
Time Frame: 2 years
Number of serious adverse events are defined according to "Common Terminology Criteria for Adverse Events" (CTCAE), version 4.0
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Italiana Linfomi ONLUS

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2014

Primary Completion (Actual)

November 1, 2017

Study Completion (Actual)

July 22, 2020

Study Registration Dates

First Submitted

February 13, 2015

First Submitted That Met QC Criteria

February 24, 2015

First Posted (Estimate)

February 25, 2015

Study Record Updates

Last Update Posted (Actual)

December 2, 2020

Last Update Submitted That Met QC Criteria

December 1, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FIL_BRB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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