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

Follicular Lymphoma Clinical Trial

— FLE09  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01523860
• Other study ID #: IIL_FLE09
• Status: Completed
• Phase: Phase 2
• First received: June 23, 2011
• Last updated: February 29, 2016
• Start date: June 2009
• Est. completion date: January 2015

Study information

• Verified date: February 2016
• Source: Fondazione Italiana Linfomi ONLUS
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years to 80 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

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

Locations

Country	Name	City	State
Italy	Divisione di Ematologia Ospedale SS. Antonio e Biagio	Alessandria
Italy	SOS Ematologia Ospedale C. Massaia	Asti
Italy	Divisione di Oncologia Medica A, Centro di Riferimento Oncologico	Aviano	Pordenone
Italy	Ematologia con Trapianto, Università di Bari	Bari
Italy	Medicina Interna, Ospedale degli Infermi	Biella
Italy	Istituto di Ematologia ed Oncologia Medica A. Seragnoli Policlinico S. Orsola	Bologna
Italy	Divisione di Ematologia e TMO, Ospedale di Bolzano	Bolzano
Italy	S.C. di Ematologia, Spedali Civili	Brescia
Italy	Divisione di Ematologia, Ospedale Businco	Cagliari
Italy	Divisione di Ematologia, Ospedale di Catania	Catania
Italy	Azienda Ospedaliera Santa Croce e Carle	Cuneo
Italy	Clinica Ematologica Policlinico Carreggi	Firenze
Italy	Divisione di Ematologia, Policlinico Careggi	Firenze
Italy	Ematologia I, A.O.U. San Martino	Genova
Italy	S.C. Medicina Trasfusionale ed Ematologia , P.O. Ivrea	Ivrea
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)	Meldola	Forlì-Cesena
Italy	S.C. Ematologia, Azienda Ospedaliera Papardo	Messina
Italy	Divisione di Ematologia, Ospedale Niguarda	Milano
Italy	Ematologia e Trapianto IRCCS, Istituto Nazionale dei Tumori	Milano
Italy	Policlinico La Marcora	Milano
Italy	Ematologia, A.O. San Gerardo	Monza	Milano
Italy	UO Ematologia, II Facoltà di Medicina e Chirurgia Università Federico II	Napoli
Italy	SCDU Ematologia, AOU Maggiore della Carità	Novara
Italy	UO Ematologia, Università - Policlinico San Matteo	Pavia
Italy	Ematologia Ospedale Santa Maria delle Croci	Ravenna
Italy	Div. Ematologia A.O. "Bianchi Melacrino Morelli"	Reggio Calabria
Italy	UO Oncologia ed Onco-Ematologia, Ospedale di Rimini	Rimini	Rn
Italy	Dipartimento di biotecnologie cellulari ed ematologia Ospedale Umberto I, Università La Sapienza	Roma
Italy	Università Cattolica del Sacro Cuore	Roma
Italy	Oncologia Medica ed Ematologia, Istituto Clinica Humanitas	Rozzano	Milano
Italy	Ospedale Santa Maria di Terni	Terni
Italy	Osp. San Giovanni Battista - Biologia Molecolare	Torino
Italy	Osp. San Giovanni Battista - Ematologia 2	Torino
Italy	Ospedale S. Chiara	Trento
Italy	Ematologia Ospedale Santa Maria Di Ca' Foncello	Treviso
Italy	Ematologia e Trapianto Ospedale Card.Panico	Tricase	Lecce
Italy	Clinica di Ematologia, A.O.U. di Udine	Udine

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione Italiana Linfomi ONLUS	Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response (CR) Rate at the end of the consolidation phase	Proportion of CR according to the Cheson 2007 response criteria	6 months	No
Secondary	Progression-free survival (PFS)	PFS will be measured from the day of enrolment to the date of disease progression, relapse or death due to any cause.	24 months	No
Secondary	Molecular response rate (Bcl2/IgH rearrangement)	Rate of conversion to molecular remission by qualitative and quantitative PCR only in patients with a positive marker at baseline	24 months	No
Secondary	Molecular relapse rate	Rate of conversion to molecular relapse measured by PCR only in patients with a positive marker at baseline	24 moths	No
Secondary	Incidence of grade 3 or greater overall toxicities measured by CTCAE v.3.0		24 months	Yes
Secondary	Overall survival (OS)	OS will be measured from the day of enrolment to the date of death due to any cause.	24 moths	No