Rituximab Plus Bendamustine as Front Line Treatment in Frail Elderly (>70 Years) Patients With DLBCL: a Phase II Multicenter Study of the FIL

Sponsor

Fondazione Italiana Linfomi ONLUS (Other)

Overall Status

Unknown status

CT.gov ID

NCT01990144

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

0.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate feasibility and efficacy of rituximab-bendamustine (R-B)combination in elderly patients affected by diffuse large B-cell lymphoma and defined as frail according to CGA.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-cell Lymphoma	Drug: Bendamustine+Rituximab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

49 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Rituximab Plus Bendamustine as Front Line Treatment in Frail Elderly (>70 Years) Patients With Diffuse Large B-cell Non-Hodgkin's Lymphoma: a Phase II Multicenter Study of the Fondazione Italiana Linfomi (FIL)

Study Start Date :

Nov 1, 2011

Anticipated Primary Completion Date :

Feb 1, 2014

Anticipated Study Completion Date :

Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bendamustine Bendamustine is a novel chemotherapeutic agent, a hybrid of a purine analogue and an alkylator. It shows only partial in vitro cross-resistance with other alkylating agents and it is clinically well tolerated. In fact it has shown to be active in vitro against cell lines which are resistant to other alkylating agents. Preclinical data demonstrate that bendamustine acts in two distinct ways to kill cancer cells: it damages the DNA in cancer cells, which leads to cell death by a process known as apoptosis (programmed cell death) as well as by an alternate cell death pathway known as mitotic catastrophe (a disruption of normal cell division). This dual-effect may be attributable to its unique chemical structure.Bendamustine has demonstrated clinical activity in patients with chronic lymphocytic leukaemia, patients with relapsed indolent NHL, mantle cell lymphoma, multiple myeloma and several solid tumors.	Drug: Bendamustine+Rituximab Patients will receive : Rituximab 375 mg/m2 intravenously on day 1* Bendamustine 90 mg/m2 intravenously on days 2 and 3** Treatment will be administered on a 28-day cycle basis. Administration of rituximab during cycle 1 is postponed to day 8, thereafter on day 1. After the first cycle, bendamustine can be administered on days 1-2 or days 2-3 according to Institutional/patient/physician choice.

Arm

Intervention/Treatment

Experimental: Bendamustine

Bendamustine is a novel chemotherapeutic agent, a hybrid of a purine analogue and an alkylator. It shows only partial in vitro cross-resistance with other alkylating agents and it is clinically well tolerated. In fact it has shown to be active in vitro against cell lines which are resistant to other alkylating agents. Preclinical data demonstrate that bendamustine acts in two distinct ways to kill cancer cells: it damages the DNA in cancer cells, which leads to cell death by a process known as apoptosis (programmed cell death) as well as by an alternate cell death pathway known as mitotic catastrophe (a disruption of normal cell division). This dual-effect may be attributable to its unique chemical structure.Bendamustine has demonstrated clinical activity in patients with chronic lymphocytic leukaemia, patients with relapsed indolent NHL, mantle cell lymphoma, multiple myeloma and several solid tumors.

Drug: Bendamustine+Rituximab

Patients will receive : Rituximab 375 mg/m2 intravenously on day 1* Bendamustine 90 mg/m2 intravenously on days 2 and 3** Treatment will be administered on a 28-day cycle basis. Administration of rituximab during cycle 1 is postponed to day 8, thereafter on day 1. After the first cycle, bendamustine can be administered on days 1-2 or days 2-3 according to Institutional/patient/physician choice.

Outcome Measures

Primary Outcome Measures

To evaluate the activity of R-B combination in terms of complete response rate (CRR). [4 years]
To evaluate the safety and tolerability of R-B combination in terms of rate of adverse events occurrence. [4 years]

Secondary Outcome Measures

To evaluate progression free survival (PFS) [4 years]
To evaluate overall survival (OS) [4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Histologically proven CD20 positive diffuse large B-cell non-Hodgkin's lymphoma
Age > 70 years
No previous treatment
FRAIL patients defined as follows (see Appendices B-E) Age > 80 years with UNFIT profile, i.e.
ADL > 5 residual functions
IADL > 6 residual functions
CIRS 5-8 co-morbidities of grade 2

or Age < 80 years with

ADL < 4 residual functions, or
IADL < 5 residual functions, or
CIRS : 1 co-morbidity of grade 3-4, or > 8 co-morbidities of grade 2
Life expectancy > 6 months
Written informed consent
Accessibility of patient for treatment and follow up

Exclusion Criteria:

History of other malignancies within 5 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer
Previous exposure to cytotoxic agents
Suspect or clinical evidence of CNS involvement by lymphoma
HBsAg, HCV or HIV positivity; HBcAb positivity is accepted only with concomitant treatment with Lamivudine
AST /ALT > twice upper the normal range; bilirubin > twice upper the normal range; serum creatinine > 2.5 mg /dl
Evidence of any severe active acute or chronic infection
Concurrent co-morbid medical condition which might exclude administration of full dose chemotherapy
Senile dementia
Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ente Eccl.Osp.Gen.Reg.'Miulli'	Acquaviva Delle Fonti	Bari	Italy	70124
2	Ospedale S. Nicola Pellegrino Di Trani	Trani	Barletta	Italy	76125
3	Irccs Ospedale Casa Sollievo Della Sofferenza	San Giovanni Rotondo	Foggia	Italy	71013
4	Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori	Meldola	Forlì-Cesena	Italy	47014
5	Ospedale Generale Di Zona	Civitanova Marche	Macerata	Italy	62012
6	Nuovo Ospedale Di Sassuolo S.P.A.	Sassuolo	Modena	Italy	41049
7	Irccs Centro Di Riferimento Oncologico (Cro)	Aviano	Pordenone	Italy	33081
8	Irccs Centro Di Riferimento Oncologico Di Basilicata (Crob)	Rionero in Vulture	Potenza	Italy	85128
9	Ospedale Bianchi - Melacrino - Morelli	Reggio Di Calabria	Reggio Calabria	Italy	89124
10	P.O. Umberto I	Nocera Inferiore	Salerno	Italy	84014
11	Ospedale Civile Di Ivrea	Ivrea	Torino	Italy	10015
12	Ospedale Civile Ss. Antonio E Biagio Di Alessandria	Alessandria		Italy	15121
13	Asp Di Bolzano - Comprensorio Sanitario Di Bolzano	Bolzano		Italy	39100
14	Pres.Ospedal.Spedali Civili Brescia	Brescia		Italy	25123
15	Stabilimento "Perrino"	Brindisi		Italy	72100
16	Ospedale Armando Businco -	Cagliari		Italy	09123
17	A.O. Universitaria Ospedale Vittorio Emanuele E Ferrarotto Di Catania	Catania		Italy	95124
18	Nuovo Ospedale Garibaldi - Nesima	Catania		Italy	95124
19	Osp.Generale Di Zona Valduce	Como		Italy	22100
20	Presidio Ospedaliero Annunziata	Cosenza		Italy	87100
21	A.O. Universitaria S. Martino Di Genova	Genova		Italy	16132
22	Presidio Ospedaliero Matera	Matera		Italy	75100
23	A.O. Universitaria Policlinico Martino Di Messina	Messina		Italy	98125
24	Azienda Ospedaliera Papardo	Messina		Italy	98158
25	Irccs Istituto Nazionale Dei Tumori (Int)	Milano		Italy	20133
26	Ospedale S. Carlo Borromeo	Milano		Italy	20153
27	Ospedale Ca' Granda-Niguarda	Milano		Italy	20162
28	A.O. Universitaria Policlinico Di Modena	Modena		Italy	41124
29	Azienda Ospedaliera S. Gerardo Di Monza	Monza		Italy	20900
30	Irccs Istituto Oncologico Veneto (Iov)	Padova		Italy	35128
31	A.O. Universitaria Policlinico Giaccone Di Palermo	Palermo		Italy	90127
32	A.O. "V. Cervello"	Palermo		Italy	90146
33	Casa Di Cura La Maddalena Di Palermo	Palermo		Italy	90146
34	A.O. Universitaria Di Parma	Parma		Italy	43126
35	Ospedale Civile Spirito Santo	Pescara		Italy	65100
36	Ausl Di Piacenza	Piacenza		Italy	29121
37	A.O. Universitaria Pisana	Pisa		Italy	56126
38	Ospedale S. Maria Delle Croci Di Di Ravenna	Ravenna		Italy	48121
39	Ospedale Di S. Maria Nuova	Reggio Emilia		Italy	42100
40	Ospedale Di Rimini	Rimini		Italy	47900
41	Irccs Istituto Regina Elena (Ifo)	Roma		Italy	00144
42	Ospedale S. Eugenio	Roma		Italy	00144
43	Azienda Osp. S.Giovanni/Addolorata Roma	Roma		Italy	00184
44	A.O.Oo.Rr.S.Giovanni Di Dio E Ruggi D'Ar	Salerno		Italy	84100
45	A.O. Universitaria Policlinico Di Sassari	Sassari		Italy	07100
46	A.O. Universitaria Senese	Siena		Italy	53100
47	Stabilimento Ss. Annunziata	Taranto		Italy	74100
48	Azienda Ospedaliera "S. Maria"	Terni		Italy	05100
49	Ematologia 1 - A.O. UNIVERSITARIA S. GIOVANNI BATTISTA-MOLINETTE DI TORINO	Torino		Italy	10126
50	Ematologia 2 - A.O. UNIVERSITARIA S. GIOVANNI BATTISTA-MOLINETTE DI TORINO	Torino		Italy	10126
51	Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI	Varese		Italy	21100
52	Oncologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI	Varese		Italy	21100

Sponsors and Collaborators

Fondazione Italiana Linfomi ONLUS

Investigators

Principal Investigator: Michele Spina, MD, IRCCS CENTRO DI RIFERIMENTO ONCOLOGICO (CRO) - AVIANO (PN)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Fondazione Italiana Linfomi ONLUS

ClinicalTrials.gov Identifier:

NCT01990144

Other Study ID Numbers:

FIL_R-BENDA FRAIL

First Posted:

Nov 21, 2013

Last Update Posted:

Nov 21, 2013

Last Verified:

Nov 1, 2013

Additional relevant MeSH terms:

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Rituximab

Bendamustine Hydrochloride

Study Results

No Results Posted as of Nov 21, 2013