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

NCT02371148 | Completed Phase 2

• 1 other identifier: FIL_BRB
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 23

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.

Conditions

Waldenstrom's Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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 Outcomes (4)

• Overall Response Rate (ORR)

  2 years

• Overall Survival (OS)

  2 years

• Toxicity

  2 years

• Number of serious adverse events

  2 years

Study Arms (1)

Bortezomib-Rituximab-Bendamustine

EXPERIMENTAL

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

Drug: Bortezomib-Rituximab-Bendamustine

Interventions

Bortezomib-Rituximab-Bendamustine 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

Also known as: BRB

Bortezomib-Rituximab-Bendamustine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (23)

AO Riuniti Papardo Piemonte

Messina, ME, 98158, Italy

Location

Centro di Riferimento Oncologico della Basilicata

Rionero in Vulture, PZ, 85028, Italy

Location

AUSL di Ravenna

Ravenna, RA, 48100, Italy

Location

A.O. Bianchi - Melacrino - Morelli

Reggio Calabria, RC, 89125, Italy

Location

Nuovo Regina Margherita

Roma, RM, 00153, Italy

Location

Uo Oncoematologia, Po "A.Tortora"

Pagani, Salerno, 84016, Italy

Location

Ospedale S. Giacomo di Castelfranco Veneto

Castelfranco Veneto, Treviso, 31033, Italy

Location

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

Alessandria, 15121, Italy

Location

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

Ancona, 60126, Italy

Location

Centro di riferimento Oncologico - Oncologia Medica A

Aviano (PN), Italy

Location

A.O. Ospedale Degli Infermi

Biella, 13900, Italy

Location

Ospedale Businco, Divisione di Ematologia

Cagliari, Italy

Location

Area Vasta Romagna e IRST

Meldola (FC), Italy

Location

Irccs Ospedale Maggiore Policlinico Di Milano

Milan, 20122, Italy

Location

A.O. Universitaria Policlinico Di Modena

Modena, 41124, Italy

Location

Ospedale Maggiore Della Carita' - Scdu Ematologia

Novara, 28100, Italy

Location

Ospedale San Martino, Asl Oristano- Ematologia

Oristano, 09170, Italy

Location

Ematologia Policlinico San Matteo

Pavia, 27100, Italy

Location

Ausl Di Piacenza

Piacenza, 29121, Italy

Location

Ausl Di Rimini

Rimini, 47924, Italy

Location

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

Torino, 10126, Italy

Location

Città della Salute e della Scienza SC Ematologia

Torino, Italy

Location

Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI

Varese, 21100, Italy

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2015
• First Posted: February 25, 2015
• Study Start: June 1, 2014
• Primary Completion: November 1, 2017
• Study Completion: July 22, 2020
• Last Updated: December 2, 2020

Record last verified: 2020-11

Locations

IT (23)