A Phase II Study for Patients With Indolent Non-follicular Non-Hodgkin's Lymphoma (IIL INFL09)
Primary Purpose
Indolent Non-follicular, Non-Hodgkin's Lymphoma
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Bendamustine
Sponsored by
About this trial
This is an interventional treatment trial for Indolent Non-follicular focused on measuring INFL, Indolent non-follicular, untreated INFL
Eligibility Criteria
Inclusion Criteria:
- Understand and voluntarily sign an informed consent form
Histological (bone marrow or lymph nodes biopsy) proven diagnosis of B-cell CD20- positive non-follicular NHL according to REAL/WHO Classification:
i. small lymphocytic lymphoma-SLL (bone marrow or lymph nodes biopsy ii. lymphoplasmacytic/citoid lymphoma/ Waldenstrom macroglobulinemia(bone marrow or lymph nodes biopsy) iii. nodal marginal zone lymphoma (lymph nodes biopsy)
- Untreated patients
- Stage III or IV or stage II with more than three involved sites
Presence of at least one of the following criteria for the definition of active disease:
- Systemic symptoms
- Hemoglobin less than 10 g/dL (due to lymphoma)
- Platelets less than 100 x 10 9/L (due to lymphoma)
- Diffuse bone marrow infiltrate
- Lymphocyte doubling time less than 12 months (in leukemic cases)
- Bulky disease (>7 cm)
- Aged 18 - 75 Life expectancy >6 months
- ECOG performance status 0-2
- LVEF ≥45% or FS ≥37%
- ANC ≥1 x 10 9/l and Platelets count ≥75 x 10 9/l, unless due to bone marrow involvement by follicular lymphoma
- Creatinine up to 1.5 x ULN
- Conjugated bilirubin up to 2 x ULN
- Alkaline phosphatase and transaminases up to 2 x ULN
- Written informed content
Exclusion Criteria:
- Patients with diagnosis of marginal zone lymphoma of splenic or MALT origin
- Patients with diagnosis of typical Chronic Lymphocytic Leukemia (CLL)
- Men 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 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
- 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 negative and Ab anti-Hbcore positive(these patientes need to receive prophylaxis with Lamivudine)
- HCV positivity with the exception of patients with HCV RNA negative.
- CNS involvement by lymphoma
- Participation at the same time in another study in with investiogational 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
- SC Ematologia - AO SS. Antonio e Biagio e C. Arrigo
- SC Ematologia Spedali Civili
- Divisione di Ematologia e Trapianti, Ospedale San Maurizio
- Divisione di Ematologia, Centro Trapianto di Cellule Staminali
- Divisione Ematologia I , Ospedale San Martino
- S.C. Ematologia Azienda Ospedaliera Papardo
- Divisione di Oncologia Medica ed Ematologia, Istituto Clinico Humanitas
- Divisione di Ematologia Ospedale Niguarda
- Centro Oncologico Modenese
- Ematologia Azienda Ospedaliero Universitaria Paolo Giaccone
- Div. Oncologia Medica - CRO, Centro di Riferimento Oncologico
- UOC Ematologia 1/CTMO, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
- Oncoematologia Istituto Pascale
- S.C.D.U Ematologia Azienda Ospedaliero Universitaria Maggiore
- UO Ematologia Università - Policlinico San Matteo
- Ematologia Ospedale Santo Spirito
- UOA Ematologia, Ospedale Civile Ospedale G. da Saliceto
- Div. Ematologia AO Bianchi Melacrino Morelli
- Ematologia, Azienda Ospedaliera Arcispedale "S.Maria Nuova"
- Ematologia, Università "La Sapienza"
- Clinica Ematologia Policlino Le Scotte
- Struttura Complessa di Onco-Ematologia Azienda Ospedaliera S.Maria
- SC Ematologia - Città della Salute e della Scienza
- SC Ematologia U - Città della Salute e della Scienza
- Clinica Ematologica e Unità di Terapie Cellulari 'Carlo Melzi' AOU S. Maria della Misericordia
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rituximab - Bendamustine (RB)
Arm Description
1 arm: Rituximab - Bendamustine (RB) 1 arm for all patients
Outcomes
Primary Outcome Measures
Complete remission rate (CR)
Evaluated at the end of treatment
Secondary Outcome Measures
Safety analysis
Evaluated during and at the end of treatment. Percentage of patients with adverse, hematological and non-hematological toxic events
Overall response rate (ORR)
Evaluated at the end of treatment. Complete plus partial remission.
Overall survival (OS)
Dead for any causes after diagnosis. Evaluated by means of Kaplan-Meier method.
Progression free survival (PFS)
Progression, relapse or dead for any causes after diagnosis. Evaluated by means of Kaplan-Meier method.
Disease free survival (PFS)
Relapse or dead for any causes from the end of treatment, for patients in CR after B+R. Evaluated by means of Kaplan-Meier method.
Full Information
NCT ID
NCT01929265
First Posted
August 22, 2013
Last Updated
October 12, 2017
Sponsor
Fondazione Italiana Linfomi - ETS
1. Study Identification
Unique Protocol Identification Number
NCT01929265
Brief Title
A Phase II Study for Patients With Indolent Non-follicular Non-Hodgkin's Lymphoma
Acronym
IIL INFL09
Official Title
A Phase II Study of Bendamustine in Combination With Rituximab as Initial Treatment for Patients With Indolent Non-follicular Non-Hodgkin's Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
May 2015 (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 a chemoimmunotherapy with the combination of Bendamustine + Rituximab in patients with advanced untreated Indolent non Follicular non-Hodgkin Lymphomas (INFL).
Detailed Description
This is a prospective, multicenter phase II trial designed to determine efficacy and safety of a chemoimmunotherapy with the combination of Bendamustine + Rituximab in patients with advanced untreated Indolent non Follicular non-Hodgkin Lymphomas (INFL).
The study includes and induction phase and a consolidation phase.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Indolent Non-follicular, Non-Hodgkin's Lymphoma
Keywords
INFL, Indolent non-follicular, untreated INFL
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
73 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab - Bendamustine (RB)
Arm Type
Experimental
Arm Description
1 arm: Rituximab - Bendamustine (RB)
1 arm for all patients
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
RIBOMUSTIN
Intervention Description
INDUCTION PHASE
Rituximab - Bendamustine (RB): cycles 1 to 4 (0, 4, 8, 12 week):
Rituximab: 375 mg/sqm iv, day 1*
Bendamustine: 90 mg/sqm iv, days 1-2 or days 2-3 according to istitutional/patient/physician choice
Repeat cycles every 28 days for a total of 4 cycles
*In cycle 1, in order to avoid tumor lysis syndrome, Rituximab will be given on day 8.
CONSOLIDATION PHASE
Rituximab - Bendamustine (RB): cycles 5 to 6 (16, 20 week):
Rituximab: 375 mg/sqm iv day 1
Bendamustine: 90 mg/sqm iv days 1-2 or days 2-3 according to istitutional/patient/physician choice
Rituximab two monthly doses
Rituximab: 375 mg/sqm iv week 24 and 28
Primary Outcome Measure Information:
Title
Complete remission rate (CR)
Description
Evaluated at the end of treatment
Time Frame
5 months
Secondary Outcome Measure Information:
Title
Safety analysis
Description
Evaluated during and at the end of treatment. Percentage of patients with adverse, hematological and non-hematological toxic events
Time Frame
5 months
Title
Overall response rate (ORR)
Description
Evaluated at the end of treatment. Complete plus partial remission.
Time Frame
5 months
Title
Overall survival (OS)
Description
Dead for any causes after diagnosis. Evaluated by means of Kaplan-Meier method.
Time Frame
at 2 years
Title
Progression free survival (PFS)
Description
Progression, relapse or dead for any causes after diagnosis. Evaluated by means of Kaplan-Meier method.
Time Frame
at 2 years
Title
Disease free survival (PFS)
Description
Relapse or dead for any causes from the end of treatment, for patients in CR after B+R. Evaluated by means of Kaplan-Meier method.
Time Frame
at 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Understand and voluntarily sign an informed consent form
Histological (bone marrow or lymph nodes biopsy) proven diagnosis of B-cell CD20- positive non-follicular NHL according to REAL/WHO Classification:
i. small lymphocytic lymphoma-SLL (bone marrow or lymph nodes biopsy ii. lymphoplasmacytic/citoid lymphoma/ Waldenstrom macroglobulinemia(bone marrow or lymph nodes biopsy) iii. nodal marginal zone lymphoma (lymph nodes biopsy)
Untreated patients
Stage III or IV or stage II with more than three involved sites
Presence of at least one of the following criteria for the definition of active disease:
Systemic symptoms
Hemoglobin less than 10 g/dL (due to lymphoma)
Platelets less than 100 x 10 9/L (due to lymphoma)
Diffuse bone marrow infiltrate
Lymphocyte doubling time less than 12 months (in leukemic cases)
Bulky disease (>7 cm)
Aged 18 - 75 Life expectancy >6 months
ECOG performance status 0-2
LVEF ≥45% or FS ≥37%
ANC ≥1 x 10 9/l and Platelets count ≥75 x 10 9/l, unless due to bone marrow involvement by follicular lymphoma
Creatinine up to 1.5 x ULN
Conjugated bilirubin up to 2 x ULN
Alkaline phosphatase and transaminases up to 2 x ULN
Written informed content
Exclusion Criteria:
Patients with diagnosis of marginal zone lymphoma of splenic or MALT origin
Patients with diagnosis of typical Chronic Lymphocytic Leukemia (CLL)
Men 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 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
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 negative and Ab anti-Hbcore positive(these patientes need to receive prophylaxis with Lamivudine)
HCV positivity with the exception of patients with HCV RNA negative.
CNS involvement by lymphoma
Participation at the same time in another study in with investiogational 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
Luca Baldini, Prof.
Organizational Affiliation
UOC Ematologia 1/CTMO, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Official's Role
Principal Investigator
Facility Information:
Facility Name
SC Ematologia - AO SS. Antonio e Biagio e C. Arrigo
City
Alessandria
State/Province
AL
ZIP/Postal Code
15121
Country
Italy
Facility Name
SC Ematologia Spedali Civili
City
Brescia
State/Province
BS
Country
Italy
Facility Name
Divisione di Ematologia e Trapianti, Ospedale San Maurizio
City
Bolzano
State/Province
BZ
Country
Italy
Facility Name
Divisione di Ematologia, Centro Trapianto di Cellule Staminali
City
San Giovanni Rotondo
State/Province
Foggia
Country
Italy
Facility Name
Divisione Ematologia I , Ospedale San Martino
City
Genova
State/Province
GE
Country
Italy
Facility Name
S.C. Ematologia Azienda Ospedaliera Papardo
City
Messina
State/Province
ME
Country
Italy
Facility Name
Divisione di Oncologia Medica ed Ematologia, Istituto Clinico Humanitas
City
Rozzano
State/Province
Milano
Country
Italy
Facility Name
Divisione di Ematologia Ospedale Niguarda
City
Milano
State/Province
MI
Country
Italy
Facility Name
Centro Oncologico Modenese
City
Modena
State/Province
MO
Country
Italy
Facility Name
Ematologia Azienda Ospedaliero Universitaria Paolo Giaccone
City
Palermo
State/Province
PA
Country
Italy
Facility Name
Div. Oncologia Medica - CRO, Centro di Riferimento Oncologico
City
Aviano
State/Province
PN
Country
Italy
Facility Name
UOC Ematologia 1/CTMO, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
City
Milano
Country
Italy
Facility Name
Oncoematologia Istituto Pascale
City
Napoli
Country
Italy
Facility Name
S.C.D.U Ematologia Azienda Ospedaliero Universitaria Maggiore
City
Novara
Country
Italy
Facility Name
UO Ematologia Università - Policlinico San Matteo
City
Pavia
Country
Italy
Facility Name
Ematologia Ospedale Santo Spirito
City
Pescara
Country
Italy
Facility Name
UOA Ematologia, Ospedale Civile Ospedale G. da Saliceto
City
Piacenza
Country
Italy
Facility Name
Div. Ematologia AO Bianchi Melacrino Morelli
City
Reggio Calabria
Country
Italy
Facility Name
Ematologia, Azienda Ospedaliera Arcispedale "S.Maria Nuova"
City
Reggio Emilia
Country
Italy
Facility Name
Ematologia, Università "La Sapienza"
City
Roma
Country
Italy
Facility Name
Clinica Ematologia Policlino Le Scotte
City
Siena
Country
Italy
Facility Name
Struttura Complessa di Onco-Ematologia Azienda Ospedaliera S.Maria
City
Terni
Country
Italy
Facility Name
SC Ematologia - Città della Salute e della Scienza
City
Torino
Country
Italy
Facility Name
SC Ematologia U - Città della Salute e della Scienza
City
Torino
Country
Italy
Facility Name
Clinica Ematologica e Unità di Terapie Cellulari 'Carlo Melzi' AOU S. Maria della Misericordia
City
Udine
Country
Italy
12. IPD Sharing Statement
Learn more about this trial
A Phase II Study for Patients With Indolent Non-follicular Non-Hodgkin's Lymphoma
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