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

Waldenstrom's Macroglobulinemia Clinical Trial

— FIL_BRB  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02371148
• Other study ID #: FIL_BRB
• Status: Completed
• Phase: Phase 2
• Start date: June 2014
• Est. completion date: July 22, 2020

Study information

• Verified date: November 2020
• Source: Fondazione Italiana Linfomi ONLUS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: July 22, 2020
• Est. primary completion date: November 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Waldenstrom Macroglobulinemia
• Waldenstrom's Macroglobulinemia

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Italiana Linfomi ONLUS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Response Rate (ORR)	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
Secondary	Overall Survival (OS)	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
Secondary	Toxicity	Toxicity: severe, life- threatening, fatal (grade 3, 4 and 5)	2 years
Secondary	Number of serious adverse events	Number of serious adverse events are defined according to "Common Terminology Criteria for Adverse Events" (CTCAE), version 4.0	2 years