Clinical trial NCT02371148: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Waldenstrom's Macroglobulinemia
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2015-02-25
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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%.

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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 18 months
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Toxicity
timeFrame: 2 years
measure: Number of serious adverse events
timeFrame: 2 years
Other outcomes:
Locations:
city: Messina
country: Italy
facility: AO Riuniti Papardo Piemonte
state: ME
city: Rionero in Vulture
country: Italy
facility: Centro di Riferimento Oncologico della Basilicata
state: PZ
city: Ravenna
country: Italy
facility: AUSL di Ravenna
state: RA
city: Reggio Calabria
country: Italy
facility: A.O. Bianchi - Melacrino - Morelli
state: RC
city: Roma
country: Italy
facility: Nuovo Regina Margherita
state: RM
city: Pagani
country: Italy
facility: Uo Oncoematologia, Po "A.Tortora"
state: Salerno
city: Castelfranco Veneto
country: Italy
facility: Ospedale S. Giacomo di Castelfranco Veneto
state: Treviso
city: Alessandria
country: Italy
facility: A.O. SS. Antonio e Biagio e C. Arrigo
city: Ancona
country: Italy
facility: A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
city: Aviano (PN)
country: Italy
facility: Centro di riferimento Oncologico - Oncologia Medica A
city: Biella
country: Italy
facility: A.O. Ospedale Degli Infermi
city: Cagliari
country: Italy
facility: Ospedale Businco, Divisione di Ematologia
city: Meldola (FC)
country: Italy
facility: Area Vasta Romagna e IRST
city: Milano
country: Italy
facility: Irccs Ospedale Maggiore Policlinico Di Milano
city: Modena
country: Italy
facility: A.O. Universitaria Policlinico Di Modena
city: Novara
country: Italy
facility: Ospedale Maggiore Della Carita' - Scdu Ematologia
city: Oristano
country: Italy
facility: Ospedale San Martino, Asl Oristano- Ematologia
city: Pavia
country: Italy
facility: Ematologia Policlinico San Matteo
city: Piacenza
country: Italy
facility: Ausl Di Piacenza
city: Rimini
country: Italy
facility: Ausl Di Rimini
city: Torino
country: Italy
facility: Ematologia 1 - A.O. Citta' Della Salute E Della Scienza Di Torino
city: Torino
country: Italy
facility: Città della Salute e della Scienza SC Ematologia
city: Varese
country: Italy
facility: Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI
Study officials:
affiliation: SC EMATOLOGIA - AO CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO
name: Lorella Orsucci, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: SC EMATOLOGIA - AO CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO
name: Giulia Benevolo, MD
role: PRINCIPAL_INVESTIGATOR
References: