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Phase II Study of Age-Adjusted Rituximab, Bendamustine, Cytarabine as Induction Therapy in Older Patients With MCL (FIL-RBAC500)

Primary Purpose

Mantle Cell Lymphoma

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Rituximab, Bendamustine, Cytarabine.
Sponsored by
Fondazione Italiana Linfomi - ETS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mantle Cell Lymphoma focused on measuring MCL, Mantle Cell Lymphoma, Older

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Previously untreated patients with MCL aged > 65 years if they are FIT according to the geriatric CGA assessment.
  • age 60-65 years not eligible to high-dose chemotherapy plus transplantation, FIT or UNFIT according to the geriatric CGA assessment.
  • ECOG performance status ≤ 2.
  • Positivity for cyclin D1 and SOX11 [the latter being mandatory in cases lacking cyclin D1- or t(11;14)-negative], CD20 and CD5.
  • Adequate renal function (Creatinine clearance > 40 mL/min), with preserved diuresis.
  • Adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN) value, total bilirubin < 2 mg/dL, unless directly attributable to the patient's tumor.
  • Hepatitis B core antibody (HBcAb) positive/HBsAg negative/HBV-DNA negative patients may be enrolled if correct antiviral prophylaxis is administered at least 2 weeks before initiating protocol treatment.
  • Written informed consent.

Exclusion Criteria:

  • Human immunodeficiency virus (HIV) positive.
  • Previous treatment for lymphoma
  • Medical conditions or organ injuries that could interfere with administration of therapy.
  • Active bacterial, viral, or fungal infection requiring systemic therapy.
  • Seizure disorders requiring anticonvulsant therapy.
  • Severe chronic obstructive pulmonary disease with hypoxemia.
  • History of severe cardiac disease: New York Heart Association (NYHA) functional class III-IV, myocardial infarction within 6 months, ventricular tachyarrhythmias, dilatative cardiomyopathy, or unstable angina.
  • Uncontrolled diabetes mellitus.
  • Active secondary malignancy.
  • Known hypersensitivity or anaphylactic reactions to murine antibodies and proteins, to Bendamustine or mannitol.
  • Major surgery within 4 weeks of study Day 1.
  • HBsAg+
  • HCVAb+ patients with active viral replication (HCV-RNA+ with AST > 2 x normal limit)
  • Any co-existing medical or psychological condition that would preclude participation in the study or compromise the patient's ability to give informed consent, or that may affect the interpretation of the results, or render the patient at high risk from treatment complications.
  • CNS involvement (a diagnostic lumbar puncture will be performed in patients with the blastoid variant of MCL)

Sites / Locations

  • A.O. Policlinico Consorziale
  • IRCCS Ospedale Oncologico
  • A.O. Spedali Civili
  • U.O.C. Ematologia Ospedale "San Nicola Pellegrino" ASL BAT
  • Ospedale Businco
  • AO Valduce
  • U.O.C. Garibaldi Nesima
  • AOU Careggi
  • A.O.U. San Martino
  • PO Vito Fazzi
  • Ospedale Cardinale G. Panico
  • Asur - Zona Territoriale 8
  • U.O.C. Ematologia - Policlinico Universitario
  • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
  • A.O. S. Carlo Borromeo di Milano Unità Semplice di Trapianto Midollo - A.O.S.Carlo Borromeo
  • A.O. Niguarda
  • Osp. San Gerardo
  • Istituto Clinico Humanitas
  • Centro Oncologico Modenese (COM)
  • "La Maddalena"
  • Ospedali Riuniti Villa Sofia - Cervello
  • Ospedale Civile Guglielmo da Saliceto
  • Università di Padova
  • Presidio ospedaliero di Pescara
  • CRO Aviano
  • Fondazione IRCCS Policlinico San Matteo,
  • Osp. S. Maria delle Croci
  • Azienda Ospedaliera "Bianchi Melacrino Morelli"
  • Azienda Ospedaliera Arcispedale "S.Maria Nuova"
  • A.O. San Camillo Forlanini
  • Nuovo Regina Margherita
  • Università "La Sapienza"
  • A.O. S. Giovanni Addolorata
  • Ospedale degli Infermi di Rimini
  • Azienda ULSS 18
  • Osp. Umberto I
  • A.O.U. San Giovanni di Dio e Ruggi d'Aragona
  • Az. Ospedaliera Univ. Senese
  • ASL TO4
  • Ospedale S. Luigi Gonzaga,
  • A.O.U. S. Giovanni Battista -Ematologia 2
  • AOU San Giovanni Battista-Ematologia 1
  • A.O. S. Maria di Terni
  • Azienda Ospedaliero - Universitaria di Udine
  • Ospedale di Circolo e Fondazione Macchi - Ematologia
  • Ospedale di Circolo e Fondazione Macchi - Oncologia
  • Osp. S. Andrea Vercelli
  • Ospedale Civile di Mirano
  • Ospedale San Bortolo
  • Ospedale Policlinico G.B. Rossi (Borgo Roma) Di Verona
  • A.O. SS. Antonio e Biagio e C. Arrigo
  • Comprensorio sanitario di Bolzano
  • Ospedale Cardarelli
  • A.O. Pugliese-Ciacci
  • IRST
  • Università del Piemonte Orientale - Novara

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

One arm for all patients.

Arm Description

Rituximab, Bendamustine, Cytarabine

Outcomes

Primary Outcome Measures

complete remission rate at the end of treatment
The primary objective is to determine the activity [complete remission rate (CR) according to Cheson 2007 criteria]
Toxicity will be represented by the occurrence of any of the stop treatment criteria or of any episode of relevant toxicity
Relevant toxicity: Grade 4 cytopenia lasting for more than 6 days or Grade 3-4 non-hematologic toxicity or Febrile neutropenia lasting for more than 3 consecutive days. Stop treatment criteria: Occurrence of relevant toxicity for two subsequent or consecutive cycles. Grade 3-4 hematological or non-hematological toxicity on day +28 of a cycle not resolving within two weeks. Grade 3-4 hematological or non-hematological toxicity on day +28 of a cycle after 25% dose reduction. Patient refusal to procede with further cycles due to perceived excessive toxicity. Any unpredictable drug related event that suggests against study continuation

Secondary Outcome Measures

the rate of molecular response
the rate of molecular response (characterized by labs of the FIL)
the progression-free survival (PFS)
the progression-free survival (PFS)is defined as the time from enrollment to complete remission with disappearance of all evidence of disease, disease progression or relapse or death from any cause.
the overall survival (OS)
the overall survival (OS) is defined as the time from enrollment to death from any cause
the duration of responses (DOR)
the duration of responses (DOR)
the rate of completion of treatment
the rate of patients that complete the expected treatment schedule (6 courses)
the rate of dose reductions or delays
the rate of patients that are subject to dose reductions or delays

Full Information

First Posted
June 26, 2012
Last Updated
August 8, 2022
Sponsor
Fondazione Italiana Linfomi - ETS
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1. Study Identification

Unique Protocol Identification Number
NCT01662050
Brief Title
Phase II Study of Age-Adjusted Rituximab, Bendamustine, Cytarabine as Induction Therapy in Older Patients With MCL
Acronym
FIL-RBAC500
Official Title
Phase II Study of Age-Adjusted R-BAC (Rituximab, Bendamustine, Cytarabine) as Induction Therapy in Older Patients With Mantle Cell Lymphoma (MCL)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
March 20, 2012 (Actual)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
September 11, 2017 (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
A phase 2 study of standard R-BAC (rituximab 375 mg/m2, bendamustine 70 mg/m2, ara-c 800 mg/m2) has been recently ultimated at the Vicenza Hematology Department involving several regional centers on both untreated and previously treated patients with Mantle Cell Lymphoma (MCL). An interim analysis conducted on 30 patients showed that rituximab + bendamustine + ara-c combination had very good clinical activity, but a quite relevant hematological toxicity, especially in previously treated and older patients (Visco C, ICML 2011 Lugano Conference, Poster 236). Objectives: The primary objective is to determine the activity (complete remission rate according to Cheson 2007 criteria) and safety of age-adjusted Rituximab-Bendamustine-Cytarabine (RBAC500) regimen at the end of treatment in older untreated patients with MCL. The secondary objectives are to determine: The rate of molecular response (characterized by labs of the FIL) The progression-free survival (PFS) The overall survival (OS) The duration of responses (DOR) The rate of patients that complete the expected treatment schedule (6 courses) The rate of patients that are subject to dose reductions or delays
Detailed Description
Study End points Primary efficacy end point of the study is the proportion of CR defined according to Cheson criteria (2007) at the end of treatment (6 or 4 cycles). Primary safety end point is the occurrence of any of the stop treatment criteria or of any episode of relevant toxicity, as above defined. Secondary end points are MRD defined response, OS, PFS and DOR (Cheson 2007). Molecular response is the proportion of patients with molecular rearrangements at baseline that become negative during treatment, measured by qualitative and quantitative PCR. OS is measured from enrollment until death from any cause. PFS is measured from the time of enrollment until disease progression, relapse or death from any cause. DOR is measured from the first assessment that documents response (CR or PR) to the date of disease relapse or progression. Minimum follow up required for all patients will be 24 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mantle Cell Lymphoma
Keywords
MCL, Mantle Cell Lymphoma, Older

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
One arm for all patients.
Arm Type
Experimental
Arm Description
Rituximab, Bendamustine, Cytarabine
Intervention Type
Drug
Intervention Name(s)
Rituximab, Bendamustine, Cytarabine.
Intervention Description
6 cycles of 28 days with Rituximab, Bendamustine and Cytarabine (R-BAC). Rituximab 375mg/mq; Bendamustine 70mg/mq; Cytarabine 500mg/mq.
Primary Outcome Measure Information:
Title
complete remission rate at the end of treatment
Description
The primary objective is to determine the activity [complete remission rate (CR) according to Cheson 2007 criteria]
Time Frame
6 months
Title
Toxicity will be represented by the occurrence of any of the stop treatment criteria or of any episode of relevant toxicity
Description
Relevant toxicity: Grade 4 cytopenia lasting for more than 6 days or Grade 3-4 non-hematologic toxicity or Febrile neutropenia lasting for more than 3 consecutive days. Stop treatment criteria: Occurrence of relevant toxicity for two subsequent or consecutive cycles. Grade 3-4 hematological or non-hematological toxicity on day +28 of a cycle not resolving within two weeks. Grade 3-4 hematological or non-hematological toxicity on day +28 of a cycle after 25% dose reduction. Patient refusal to procede with further cycles due to perceived excessive toxicity. Any unpredictable drug related event that suggests against study continuation
Time Frame
6 months
Secondary Outcome Measure Information:
Title
the rate of molecular response
Description
the rate of molecular response (characterized by labs of the FIL)
Time Frame
6 months
Title
the progression-free survival (PFS)
Description
the progression-free survival (PFS)is defined as the time from enrollment to complete remission with disappearance of all evidence of disease, disease progression or relapse or death from any cause.
Time Frame
30 months
Title
the overall survival (OS)
Description
the overall survival (OS) is defined as the time from enrollment to death from any cause
Time Frame
30 months
Title
the duration of responses (DOR)
Description
the duration of responses (DOR)
Time Frame
30 months
Title
the rate of completion of treatment
Description
the rate of patients that complete the expected treatment schedule (6 courses)
Time Frame
6 months
Title
the rate of dose reductions or delays
Description
the rate of patients that are subject to dose reductions or delays
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Previously untreated patients with MCL aged > 65 years if they are FIT according to the geriatric CGA assessment. age 60-65 years not eligible to high-dose chemotherapy plus transplantation, FIT or UNFIT according to the geriatric CGA assessment. ECOG performance status ≤ 2. Positivity for cyclin D1 and SOX11 [the latter being mandatory in cases lacking cyclin D1- or t(11;14)-negative], CD20 and CD5. Adequate renal function (Creatinine clearance > 40 mL/min), with preserved diuresis. Adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN) value, total bilirubin < 2 mg/dL, unless directly attributable to the patient's tumor. Hepatitis B core antibody (HBcAb) positive/HBsAg negative/HBV-DNA negative patients may be enrolled if correct antiviral prophylaxis is administered at least 2 weeks before initiating protocol treatment. Written informed consent. Exclusion Criteria: Human immunodeficiency virus (HIV) positive. Previous treatment for lymphoma Medical conditions or organ injuries that could interfere with administration of therapy. Active bacterial, viral, or fungal infection requiring systemic therapy. Seizure disorders requiring anticonvulsant therapy. Severe chronic obstructive pulmonary disease with hypoxemia. History of severe cardiac disease: New York Heart Association (NYHA) functional class III-IV, myocardial infarction within 6 months, ventricular tachyarrhythmias, dilatative cardiomyopathy, or unstable angina. Uncontrolled diabetes mellitus. Active secondary malignancy. Known hypersensitivity or anaphylactic reactions to murine antibodies and proteins, to Bendamustine or mannitol. Major surgery within 4 weeks of study Day 1. HBsAg+ HCVAb+ patients with active viral replication (HCV-RNA+ with AST > 2 x normal limit) Any co-existing medical or psychological condition that would preclude participation in the study or compromise the patient's ability to give informed consent, or that may affect the interpretation of the results, or render the patient at high risk from treatment complications. CNS involvement (a diagnostic lumbar puncture will be performed in patients with the blastoid variant of MCL)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlo Visco, MD
Organizational Affiliation
Ospedale ULSS 6 di Vicenza - Ematologia
Official's Role
Principal Investigator
Facility Information:
Facility Name
A.O. Policlinico Consorziale
City
Bari
State/Province
BA
ZIP/Postal Code
70124
Country
Italy
Facility Name
IRCCS Ospedale Oncologico
City
Bari
State/Province
BA
ZIP/Postal Code
70124
Country
Italy
Facility Name
A.O. Spedali Civili
City
Brescia
State/Province
BS
ZIP/Postal Code
25100
Country
Italy
Facility Name
U.O.C. Ematologia Ospedale "San Nicola Pellegrino" ASL BAT
City
Trani
State/Province
BT
ZIP/Postal Code
70031
Country
Italy
Facility Name
Ospedale Businco
City
Cagliari
State/Province
CA
ZIP/Postal Code
09121
Country
Italy
Facility Name
AO Valduce
City
Como
State/Province
CO
ZIP/Postal Code
22100
Country
Italy
Facility Name
U.O.C. Garibaldi Nesima
City
Catania
State/Province
CT
ZIP/Postal Code
95125
Country
Italy
Facility Name
AOU Careggi
City
Firenze
State/Province
FI
ZIP/Postal Code
50134
Country
Italy
Facility Name
A.O.U. San Martino
City
Genova
State/Province
GE
ZIP/Postal Code
16132
Country
Italy
Facility Name
PO Vito Fazzi
City
Lecce
State/Province
LE
ZIP/Postal Code
73100
Country
Italy
Facility Name
Ospedale Cardinale G. Panico
City
Tricase
State/Province
LE
ZIP/Postal Code
73039
Country
Italy
Facility Name
Asur - Zona Territoriale 8
City
Civitanova Marche
State/Province
MC
ZIP/Postal Code
62012
Country
Italy
Facility Name
U.O.C. Ematologia - Policlinico Universitario
City
Messina
State/Province
ME
ZIP/Postal Code
98100
Country
Italy
Facility Name
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
City
Milano
State/Province
MI
ZIP/Postal Code
20122
Country
Italy
Facility Name
A.O. S. Carlo Borromeo di Milano Unità Semplice di Trapianto Midollo - A.O.S.Carlo Borromeo
City
Milano
State/Province
MI
ZIP/Postal Code
20153
Country
Italy
Facility Name
A.O. Niguarda
City
Milano
State/Province
MI
ZIP/Postal Code
20162
Country
Italy
Facility Name
Osp. San Gerardo
City
Monza
State/Province
MI
ZIP/Postal Code
20052
Country
Italy
Facility Name
Istituto Clinico Humanitas
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Facility Name
Centro Oncologico Modenese (COM)
City
Modena
State/Province
MO
ZIP/Postal Code
41100
Country
Italy
Facility Name
"La Maddalena"
City
Palermo
State/Province
PA
ZIP/Postal Code
90146
Country
Italy
Facility Name
Ospedali Riuniti Villa Sofia - Cervello
City
Palermo
State/Province
PA
ZIP/Postal Code
90146
Country
Italy
Facility Name
Ospedale Civile Guglielmo da Saliceto
City
Piacenza
State/Province
PC
ZIP/Postal Code
29121
Country
Italy
Facility Name
Università di Padova
City
Padova
State/Province
PD
ZIP/Postal Code
35128
Country
Italy
Facility Name
Presidio ospedaliero di Pescara
City
Pescara
State/Province
PE
ZIP/Postal Code
65124
Country
Italy
Facility Name
CRO Aviano
City
Aviano
State/Province
PN
ZIP/Postal Code
33081
Country
Italy
Facility Name
Fondazione IRCCS Policlinico San Matteo,
City
Pavia
State/Province
PV
ZIP/Postal Code
27100
Country
Italy
Facility Name
Osp. S. Maria delle Croci
City
Ravenna
State/Province
RA
ZIP/Postal Code
48121
Country
Italy
Facility Name
Azienda Ospedaliera "Bianchi Melacrino Morelli"
City
Reggio Calabria
State/Province
RC
ZIP/Postal Code
89125
Country
Italy
Facility Name
Azienda Ospedaliera Arcispedale "S.Maria Nuova"
City
Reggio Emilia
State/Province
RE
ZIP/Postal Code
42100
Country
Italy
Facility Name
A.O. San Camillo Forlanini
City
Roma
State/Province
RM
ZIP/Postal Code
00152
Country
Italy
Facility Name
Nuovo Regina Margherita
City
Roma
State/Province
RM
ZIP/Postal Code
00153
Country
Italy
Facility Name
Università "La Sapienza"
City
Roma
State/Province
RM
ZIP/Postal Code
00161
Country
Italy
Facility Name
A.O. S. Giovanni Addolorata
City
Roma
State/Province
RM
ZIP/Postal Code
00184
Country
Italy
Facility Name
Ospedale degli Infermi di Rimini
City
Rimini
State/Province
RN
ZIP/Postal Code
47900
Country
Italy
Facility Name
Azienda ULSS 18
City
Rovigo
State/Province
RO
ZIP/Postal Code
45100
Country
Italy
Facility Name
Osp. Umberto I
City
Nocera Inferiore
State/Province
SA
ZIP/Postal Code
84014
Country
Italy
Facility Name
A.O.U. San Giovanni di Dio e Ruggi d'Aragona
City
Salerno
State/Province
SA
ZIP/Postal Code
84131
Country
Italy
Facility Name
Az. Ospedaliera Univ. Senese
City
Siena
State/Province
SI
ZIP/Postal Code
53100
Country
Italy
Facility Name
ASL TO4
City
Ciriè-Ivrea-Chivasso
State/Province
TO
ZIP/Postal Code
10043
Country
Italy
Facility Name
Ospedale S. Luigi Gonzaga,
City
Orbassano
State/Province
TO
ZIP/Postal Code
10043
Country
Italy
Facility Name
A.O.U. S. Giovanni Battista -Ematologia 2
City
Torino
State/Province
TO
ZIP/Postal Code
10126
Country
Italy
Facility Name
AOU San Giovanni Battista-Ematologia 1
City
Torino
State/Province
TO
ZIP/Postal Code
10126
Country
Italy
Facility Name
A.O. S. Maria di Terni
City
Terni
State/Province
TR
ZIP/Postal Code
05100
Country
Italy
Facility Name
Azienda Ospedaliero - Universitaria di Udine
City
Udine
State/Province
UD
ZIP/Postal Code
33100
Country
Italy
Facility Name
Ospedale di Circolo e Fondazione Macchi - Ematologia
City
Varese
State/Province
VA
ZIP/Postal Code
21100
Country
Italy
Facility Name
Ospedale di Circolo e Fondazione Macchi - Oncologia
City
Varese
State/Province
VA
ZIP/Postal Code
21100
Country
Italy
Facility Name
Osp. S. Andrea Vercelli
City
Vercelli
State/Province
VC
ZIP/Postal Code
13100
Country
Italy
Facility Name
Ospedale Civile di Mirano
City
Mirano
State/Province
VE
ZIP/Postal Code
30035
Country
Italy
Facility Name
Ospedale San Bortolo
City
Vicenza
State/Province
VI
ZIP/Postal Code
36100
Country
Italy
Facility Name
Ospedale Policlinico G.B. Rossi (Borgo Roma) Di Verona
City
Verona
State/Province
VR
ZIP/Postal Code
37126
Country
Italy
Facility Name
A.O. SS. Antonio e Biagio e C. Arrigo
City
Alessandria
ZIP/Postal Code
15121
Country
Italy
Facility Name
Comprensorio sanitario di Bolzano
City
Bolzano
ZIP/Postal Code
39100
Country
Italy
Facility Name
Ospedale Cardarelli
City
Campobasso
ZIP/Postal Code
86100
Country
Italy
Facility Name
A.O. Pugliese-Ciacci
City
Catanzaro
ZIP/Postal Code
88100
Country
Italy
Facility Name
IRST
City
Meldola
ZIP/Postal Code
47014
Country
Italy
Facility Name
Università del Piemonte Orientale - Novara
City
Novara
ZIP/Postal Code
28100
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
27927586
Citation
Visco C, Chiappella A, Nassi L, Patti C, Ferrero S, Barbero D, Evangelista A, Spina M, Molinari A, Rigacci L, Tani M, Rocco AD, Pinotti G, Fabbri A, Zambello R, Finotto S, Gotti M, Carella AM, Salvi F, Pileri SA, Ladetto M, Ciccone G, Gaidano G, Ruggeri M, Martelli M, Vitolo U. Rituximab, bendamustine, and low-dose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi. Lancet Haematol. 2017 Jan;4(1):e15-e23. doi: 10.1016/S2352-3026(16)30185-5. Epub 2016 Dec 5.
Results Reference
derived

Learn more about this trial

Phase II Study of Age-Adjusted Rituximab, Bendamustine, Cytarabine as Induction Therapy in Older Patients With MCL

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