Fase II Study With BRB for Non-Hodgkin Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia's (FIL_BRB)
Primary Purpose
Waldenstrom's Macroglobulinemia
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Bortezomib-Rituximab-Bendamustine
Sponsored by
About this trial
This is an interventional treatment trial for Waldenstrom's Macroglobulinemia
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
Sites / Locations
- AO Riuniti Papardo Piemonte
- Centro di Riferimento Oncologico della Basilicata
- AUSL di Ravenna
- A.O. Bianchi - Melacrino - Morelli
- Nuovo Regina Margherita
- Uo Oncoematologia, Po "A.Tortora"
- Ospedale S. Giacomo di Castelfranco Veneto
- A.O. SS. Antonio e Biagio e C. Arrigo
- A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
- Centro di riferimento Oncologico - Oncologia Medica A
- A.O. Ospedale Degli Infermi
- Ospedale Businco, Divisione di Ematologia
- Area Vasta Romagna e IRST
- Irccs Ospedale Maggiore Policlinico Di Milano
- A.O. Universitaria Policlinico Di Modena
- Ospedale Maggiore Della Carita' - Scdu Ematologia
- Ospedale San Martino, Asl Oristano- Ematologia
- Ematologia Policlinico San Matteo
- Ausl Di Piacenza
- Ausl Di Rimini
- Ematologia 1 - A.O. Citta' Della Salute E Della Scienza Di Torino
- Città della Salute e della Scienza SC Ematologia
- Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Bortezomib-Rituximab-Bendamustine
Arm Description
Bortezomib-Rituximab-Bendamustine (BRB) combination in patients with relapsed/refractory lymphoplasmocytic/lymphoplasmocytoid lymphoma/Waldenstrom macroglobulinemia after one line of therapy.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Toxicity
Toxicity: severe, life- threatening, fatal (grade 3, 4 and 5)
Number of serious adverse events
Number of serious adverse events are defined according to "Common Terminology Criteria for Adverse Events" (CTCAE), version 4.0
Full Information
NCT ID
NCT02371148
First Posted
February 13, 2015
Last Updated
December 1, 2020
Sponsor
Fondazione Italiana Linfomi - ETS
1. Study Identification
Unique Protocol Identification Number
NCT02371148
Brief Title
Fase II Study With BRB for Non-Hodgkin Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia's
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
July 22, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione Italiana Linfomi - ETS
4. Oversight
Data Monitoring Committee
No
5. 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.
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%.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Waldenstrom's Macroglobulinemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bortezomib-Rituximab-Bendamustine
Arm Type
Experimental
Arm Description
Bortezomib-Rituximab-Bendamustine (BRB) combination in patients with relapsed/refractory lymphoplasmocytic/lymphoplasmocytoid lymphoma/Waldenstrom macroglobulinemia after one line of therapy.
Intervention Type
Drug
Intervention Name(s)
Bortezomib-Rituximab-Bendamustine
Other Intervention Name(s)
BRB
Intervention Description
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
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
2 years
Title
Overall Survival (OS)
Description
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.
Time Frame
2 years
Title
Toxicity
Description
Toxicity: severe, life- threatening, fatal (grade 3, 4 and 5)
Time Frame
2 years
Title
Number of serious adverse events
Description
Number of serious adverse events are defined according to "Common Terminology Criteria for Adverse Events" (CTCAE), version 4.0
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lorella Orsucci, MD
Organizational Affiliation
SC EMATOLOGIA - AO CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Giulia Benevolo, MD
Organizational Affiliation
SC EMATOLOGIA - AO CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO
Official's Role
Principal Investigator
Facility Information:
Facility Name
AO Riuniti Papardo Piemonte
City
Messina
State/Province
ME
ZIP/Postal Code
98158
Country
Italy
Facility Name
Centro di Riferimento Oncologico della Basilicata
City
Rionero in Vulture
State/Province
PZ
ZIP/Postal Code
85028
Country
Italy
Facility Name
AUSL di Ravenna
City
Ravenna
State/Province
RA
ZIP/Postal Code
48100
Country
Italy
Facility Name
A.O. Bianchi - Melacrino - Morelli
City
Reggio Calabria
State/Province
RC
ZIP/Postal Code
89125
Country
Italy
Facility Name
Nuovo Regina Margherita
City
Roma
State/Province
RM
ZIP/Postal Code
00153
Country
Italy
Facility Name
Uo Oncoematologia, Po "A.Tortora"
City
Pagani
State/Province
Salerno
ZIP/Postal Code
84016
Country
Italy
Facility Name
Ospedale S. Giacomo di Castelfranco Veneto
City
Castelfranco Veneto
State/Province
Treviso
ZIP/Postal Code
31033
Country
Italy
Facility Name
A.O. SS. Antonio e Biagio e C. Arrigo
City
Alessandria
ZIP/Postal Code
15121
Country
Italy
Facility Name
A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
City
Ancona
ZIP/Postal Code
60126
Country
Italy
Facility Name
Centro di riferimento Oncologico - Oncologia Medica A
City
Aviano (PN)
Country
Italy
Facility Name
A.O. Ospedale Degli Infermi
City
Biella
ZIP/Postal Code
13900
Country
Italy
Facility Name
Ospedale Businco, Divisione di Ematologia
City
Cagliari
Country
Italy
Facility Name
Area Vasta Romagna e IRST
City
Meldola (FC)
Country
Italy
Facility Name
Irccs Ospedale Maggiore Policlinico Di Milano
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
A.O. Universitaria Policlinico Di Modena
City
Modena
ZIP/Postal Code
41124
Country
Italy
Facility Name
Ospedale Maggiore Della Carita' - Scdu Ematologia
City
Novara
ZIP/Postal Code
28100
Country
Italy
Facility Name
Ospedale San Martino, Asl Oristano- Ematologia
City
Oristano
ZIP/Postal Code
09170
Country
Italy
Facility Name
Ematologia Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Ausl Di Piacenza
City
Piacenza
ZIP/Postal Code
29121
Country
Italy
Facility Name
Ausl Di Rimini
City
Rimini
ZIP/Postal Code
47924
Country
Italy
Facility Name
Ematologia 1 - A.O. Citta' Della Salute E Della Scienza Di Torino
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Città della Salute e della Scienza SC Ematologia
City
Torino
Country
Italy
Facility Name
Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI
City
Varese
ZIP/Postal Code
21100
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Fase II Study With BRB for Non-Hodgkin Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia's
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