FLE09: Brief Chemoimmunotherapy With R+B+M Followed by R in Elderly Patients Advanced Stage Untreated Follicular Lymphoma

Sponsor

Fondazione Italiana Linfomi ONLUS (Other)

Overall Status

Completed

CT.gov ID

NCT01523860

Collaborator

Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte (Other)

Enrollment

Locations

Arm

Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective, multicenter phase II trial designed to determine efficacy and safety of a brief chemoimmunotherapy with the combination of Rituximab + Bendamustine + Mitoxantrone in elderly patients with advanced stage Follicular Lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma	Drug: Rituximab, Mitoxantrone, Bendamustine	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

76 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Brief Induction Chemoimmunotherapy With Rituximab + Bendamustine + Mitoxantrone Followed by Rituximab in Elderly Patients With Advanced Stage Previously Untreated Follicular Lymphoma

Study Start Date :

Jun 1, 2009

Actual Primary Completion Date :

Jan 1, 2015

Actual Study Completion Date :

Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Rituximab will be supplied as 375 mg/sqm for i.v.administration.Mitoxantrone will be supplied as 8 mg/sqm for i.v.administration.Bendamustine will be supplied as 90 mg/sqm for i.v.administration.	Drug: Rituximab, Mitoxantrone, Bendamustine Rituximab will be supplied as 375 mg/sqm for i.v.administration.Mitoxantrone will be supplied as 8 mg/sqm for i.v.administration.Bendamustine will be supplied as 90 mg/sqm for i.v.administration

Arm

Intervention/Treatment

Experimental: 1

Rituximab will be supplied as 375 mg/sqm for i.v.administration.Mitoxantrone will be supplied as 8 mg/sqm for i.v.administration.Bendamustine will be supplied as 90 mg/sqm for i.v.administration.

Drug: Rituximab, Mitoxantrone, Bendamustine

Rituximab will be supplied as 375 mg/sqm for i.v.administration.Mitoxantrone will be supplied as 8 mg/sqm for i.v.administration.Bendamustine will be supplied as 90 mg/sqm for i.v.administration

Outcome Measures

Primary Outcome Measures

Complete Response (CR) Rate at the end of the consolidation phase [6 months]
Proportion of CR according to the Cheson 2007 response criteria

Secondary Outcome Measures

Progression-free survival (PFS) [24 months]
PFS will be measured from the day of enrolment to the date of disease progression, relapse or death due to any cause.
Molecular response rate (Bcl2/IgH rearrangement) [24 months]
Rate of conversion to molecular remission by qualitative and quantitative PCR only in patients with a positive marker at baseline
Molecular relapse rate [24 moths]
Rate of conversion to molecular relapse measured by PCR only in patients with a positive marker at baseline
Incidence of grade 3 or greater overall toxicities measured by CTCAE v.3.0 [24 months]
Overall survival (OS) [24 moths]
OS will be measured from the day of enrolment to the date of death due to any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histological proven diagnosis of B-cell CD20+ follicular NHL, grade I, II and IIIa of WHO Classification
Untreated patients with the exception of prior limited radiotherapy
Stage III or IV who require therapy according to SIE and GELF criteria
Stage II with at least one of the following:
Bulky disease (>7 cm)
LDH >normal
Systemic symptoms
Beta2-Microglobulin >3 mg/l
Extra-nodal involvement
Active disease with rapid progression 5.Age from 65 to 80 years, geriatric score "FIT" (see Appendix B) 6.Life expectancy >6 months 7.ECOG performance status 0-2 (see Appendix C) 8.LVEF ≥45% or FS ≥37% 9.ANC ≥1 x 109/l and Platelets count ≥75 x 109/l, unless due to bone marrow involvement by follicular lymphoma 10.Creatinine up to 1.5 x ULN 11.Conjugated bilirubin up to 2 x ULN 12.Alkaline phosphatase and transaminases up to 2 x ULN 13.Sending of bone marrow sample for Bcl-2/IgH rearrangement evaluation 14.Written informed content

Exclusion Criteria:

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 5. Concurrent medical condition which might exclude administration of therapy
Cardiac insufficiency (NYHA grade III/IV; see Appendix D)
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 (see Appendix E)
HIV positivity
HBV positivity with the exception of patients HbsAg negative and Ab anti-Hbcore positive (these patients need to receive prophylaxis with Lamivudine)
HCV positivity with the exception of patients with no laboratory signs of active chronic hepatitis and HCV-RNA negativity
CNS involvement by lymphoma 16. Participation at the same time in another study in which 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)	Meldola	Forlì-Cesena	Italy	47014
2	Ematologia e Trapianto Ospedale Card.Panico	Tricase	Lecce	Italy
3	Ematologia, A.O. San Gerardo	Monza	Milano	Italy	20052
4	Oncologia Medica ed Ematologia, Istituto Clinica Humanitas	Rozzano	Milano	Italy	20089
5	Divisione di Oncologia Medica A, Centro di Riferimento Oncologico	Aviano	Pordenone	Italy	33081
6	UO Oncologia ed Onco-Ematologia, Ospedale di Rimini	Rimini	Rn	Italy
7	Divisione di Ematologia Ospedale SS. Antonio e Biagio	Alessandria		Italy	15100
8	SOS Ematologia Ospedale C. Massaia	Asti		Italy	14100
9	Ematologia con Trapianto, Università di Bari	Bari		Italy	70124
10	Medicina Interna, Ospedale degli Infermi	Biella		Italy	13800
11	Istituto di Ematologia ed Oncologia Medica A. Seragnoli Policlinico S. Orsola	Bologna		Italy	40138
12	Divisione di Ematologia e TMO, Ospedale di Bolzano	Bolzano		Italy	39100
13	S.C. di Ematologia, Spedali Civili	Brescia		Italy	25123
14	Divisione di Ematologia, Ospedale Businco	Cagliari		Italy	09121
15	Divisione di Ematologia, Ospedale di Catania	Catania		Italy
16	Azienda Ospedaliera Santa Croce e Carle	Cuneo		Italy	12100
17	Clinica Ematologica Policlinico Carreggi	Firenze		Italy	50134
18	Divisione di Ematologia, Policlinico Careggi	Firenze		Italy
19	Ematologia I, A.O.U. San Martino	Genova		Italy	16132
20	S.C. Medicina Trasfusionale ed Ematologia , P.O. Ivrea	Ivrea		Italy	10015
21	S.C. Ematologia, Azienda Ospedaliera Papardo	Messina		Italy	98158
22	Divisione di Ematologia, Ospedale Niguarda	Milano		Italy	20162
23	Ematologia e Trapianto IRCCS, Istituto Nazionale dei Tumori	Milano		Italy
24	Policlinico La Marcora	Milano		Italy
25	UO Ematologia, II Facoltà di Medicina e Chirurgia Università Federico II	Napoli		Italy	80131
26	SCDU Ematologia, AOU Maggiore della Carità	Novara		Italy	28100
27	UO Ematologia, Università - Policlinico San Matteo	Pavia		Italy	27100
28	Ematologia Ospedale Santa Maria delle Croci	Ravenna		Italy	48100
29	Div. Ematologia A.O. "Bianchi Melacrino Morelli"	Reggio Calabria		Italy	89100
30	Università Cattolica del Sacro Cuore	Roma		Italy	00168
31	Dipartimento di biotecnologie cellulari ed ematologia Ospedale Umberto I, Università La Sapienza	Roma		Italy
32	Ospedale Santa Maria di Terni	Terni		Italy	05100
33	Osp. San Giovanni Battista - Biologia Molecolare	Torino		Italy	10126
34	Osp. San Giovanni Battista - Ematologia 2	Torino		Italy	10126
35	Ospedale S. Chiara	Trento		Italy
36	Ematologia Ospedale Santa Maria Di Ca' Foncello	Treviso		Italy	31100
37	Clinica di Ematologia, A.O.U. di Udine	Udine		Italy	33100