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

NCT ID: NCT02371148

Last Updated: 2020-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-30

Study Completion Date

2020-07-22

Brief Summary

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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

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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%.

Conditions

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Waldenstrom's Macroglobulinemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Bortezomib-Rituximab-Bendamustine

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

Group Type EXPERIMENTAL

Bortezomib-Rituximab-Bendamustine

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Other Intervention Names

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BRB

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lorella Orsucci, MD

Role: PRINCIPAL_INVESTIGATOR

SC EMATOLOGIA - AO CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO

Giulia Benevolo, MD

Role: PRINCIPAL_INVESTIGATOR

SC EMATOLOGIA - AO CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO

Locations

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AO Riuniti Papardo Piemonte

Messina, ME, Italy

Site Status

Centro di Riferimento Oncologico della Basilicata

Rionero in Vulture, PZ, Italy

Site Status

AUSL di Ravenna

Ravenna, RA, Italy

Site Status

A.O. Bianchi - Melacrino - Morelli

Reggio Calabria, RC, Italy

Site Status

Nuovo Regina Margherita

Roma, RM, Italy

Site Status

Uo Oncoematologia, Po "A.Tortora"

Pagani, Salerno, Italy

Site Status

Ospedale S. Giacomo di Castelfranco Veneto

Castelfranco Veneto, Treviso, Italy

Site Status

A.O. SS. Antonio e Biagio e C. Arrigo

Alessandria, , Italy

Site Status

A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona

Ancona, , Italy

Site Status

Centro di riferimento Oncologico - Oncologia Medica A

Aviano (PN), , Italy

Site Status

A.O. Ospedale Degli Infermi

Biella, , Italy

Site Status

Ospedale Businco, Divisione di Ematologia

Cagliari, , Italy

Site Status

Area Vasta Romagna e IRST

Meldola (FC), , Italy

Site Status

Irccs Ospedale Maggiore Policlinico Di Milano

Milan, , Italy

Site Status

A.O. Universitaria Policlinico Di Modena

Modena, , Italy

Site Status

Ospedale Maggiore Della Carita' - Scdu Ematologia

Novara, , Italy

Site Status

Ospedale San Martino, Asl Oristano- Ematologia

Oristano, , Italy

Site Status

Ematologia Policlinico San Matteo

Pavia, , Italy

Site Status

Ausl Di Piacenza

Piacenza, , Italy

Site Status

Ausl Di Rimini

Rimini, , Italy

Site Status

Ematologia 1 - A.O. Citta' Della Salute E Della Scienza Di Torino

Torino, , Italy

Site Status

Città della Salute e della Scienza SC Ematologia

Torino, , Italy

Site Status

Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI

Varese, , Italy

Site Status

Countries

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Italy

Other Identifiers

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FIL_BRB

Identifier Type: -

Identifier Source: org_study_id