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

Sponsor
Fondazione Italiana Linfomi ONLUS (Other)
Overall Status
Completed
CT.gov ID
NCT02371148
Collaborator
(none)
38
Enrollment
23
Locations
1
Arm
73.7
Duration (Months)
1.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
38 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Fase II Study With Bortezomib, Rituximab and Bendamustin-BRB- for Non-Hodgkin Lymphoplasmocytic Lymphoma/Waldenstrom Macroglobulinemia's Patients at First Relapse
Study Start Date :
Jun 1, 2014
Actual Primary Completion Date :
Nov 1, 2017
Actual Study Completion Date :
Jul 22, 2020

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [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.

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) [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. Overall Survival (OS) [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.

    3. Toxicity [2 years]

      Toxicity: severe, life- threatening, fatal (grade 3, 4 and 5)

    4. Number of serious adverse events [2 years]

      Number of serious adverse events are defined according to "Common Terminology Criteria for Adverse Events" (CTCAE), version 4.0

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • 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 Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Fondazione Italiana Linfomi ONLUS
    ClinicalTrials.gov Identifier:
    NCT02371148
    Other Study ID Numbers:
    • FIL_BRB
    First Posted:
    Feb 25, 2015
    Last Update Posted:
    Dec 2, 2020
    Last Verified:
    Nov 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Additional relevant MeSH terms:
    Waldenstrom Macroglobulinemia
    Rituximab
    Bortezomib
    Bendamustine Hydrochloride

    Study Results

    No Results Posted as of Dec 2, 2020