Clinical trial NCT01523860: Brief Chemoimmunotherapy With R+B+M Followed by R in Elderly Patients Advanced Stage Untreated Follicular Lymphoma
Official title: Brief Induction Chemoimmunotherapy With Rituximab + Bendamustine + Mitoxantrone Followed by Rituximab in Elderly Patients With Advanced Stage Previously Untreated Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Follicular Lymphoma
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
Collaborators: name: Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte
First posted: 2012-02-01
Enrollment: 76
Sex: ALL
Minimum age (years): 65
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Complete Response (CR) Rate at the end of the consolidation phase
timeFrame: 6 months
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 24 months
measure: Molecular response rate (Bcl2/IgH rearrangement)
timeFrame: 24 months
measure: Molecular relapse rate
timeFrame: 24 moths
measure: Incidence of grade 3 or greater overall toxicities measured by CTCAE v.3.0
timeFrame: 24 months
measure: Overall survival (OS)
timeFrame: 24 moths
Other outcomes:
Locations:
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)
state: Forlì-Cesena
city: Tricase
country: Italy
facility: Ematologia e Trapianto Ospedale Card.Panico
state: Lecce
city: Monza
country: Italy
facility: Ematologia, A.O. San Gerardo
state: Milano
city: Rozzano
country: Italy
facility: Oncologia Medica ed Ematologia, Istituto Clinica Humanitas
state: Milano
city: Aviano
country: Italy
facility: Divisione di Oncologia Medica A, Centro di Riferimento Oncologico
state: Pordenone
city: Rimini
country: Italy
facility: UO Oncologia ed Onco-Ematologia, Ospedale di Rimini
state: Rn
city: Alessandria
country: Italy
facility: Divisione di Ematologia Ospedale SS. Antonio e Biagio
city: Asti
country: Italy
facility: SOS Ematologia Ospedale C. Massaia
city: Bari
country: Italy
facility: Ematologia con Trapianto, Università di Bari
city: Biella
country: Italy
facility: Medicina Interna, Ospedale degli Infermi
city: Bologna
country: Italy
facility: Istituto di Ematologia ed Oncologia Medica A. Seragnoli Policlinico S. Orsola
city: Bolzano
country: Italy
facility: Divisione di Ematologia e TMO, Ospedale di Bolzano
city: Brescia
country: Italy
facility: S.C. di Ematologia, Spedali Civili
city: Cagliari
country: Italy
facility: Divisione di Ematologia, Ospedale Businco
city: Catania
country: Italy
facility: Divisione di Ematologia, Ospedale di Catania
city: Cuneo
country: Italy
facility: Azienda Ospedaliera Santa Croce e Carle
city: Firenze
country: Italy
facility: Clinica Ematologica Policlinico Carreggi
city: Firenze
country: Italy
facility: Divisione di Ematologia, Policlinico Careggi
city: Genova
country: Italy
facility: Ematologia I, A.O.U. San Martino
city: Ivrea
country: Italy
facility: S.C. Medicina Trasfusionale ed Ematologia , P.O. Ivrea
city: Messina
country: Italy
facility: S.C. Ematologia, Azienda Ospedaliera Papardo
city: Milano
country: Italy
facility: Divisione di Ematologia, Ospedale Niguarda
city: Milano
country: Italy
facility: Ematologia e Trapianto IRCCS, Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Policlinico La Marcora
city: Napoli
country: Italy
facility: UO Ematologia, II Facoltà di Medicina e Chirurgia Università Federico II
city: Novara
country: Italy
facility: SCDU Ematologia, AOU Maggiore della Carità
city: Pavia
country: Italy
facility: UO Ematologia, Università - Policlinico San Matteo
city: Ravenna
country: Italy
facility: Ematologia Ospedale Santa Maria delle Croci
city: Reggio Calabria
country: Italy
facility: Div. Ematologia A.O. "Bianchi Melacrino Morelli"
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore
city: Roma
country: Italy
facility: Dipartimento di biotecnologie cellulari ed ematologia Ospedale Umberto I, Università La Sapienza
city: Terni
country: Italy
facility: Ospedale Santa Maria di Terni
city: Torino
country: Italy
facility: Osp. San Giovanni Battista - Biologia Molecolare
city: Torino
country: Italy
facility: Osp. San Giovanni Battista - Ematologia 2
city: Trento
country: Italy
facility: Ospedale S. Chiara
city: Treviso
country: Italy
facility: Ematologia Ospedale Santa Maria Di Ca' Foncello
city: Udine
country: Italy
facility: Clinica di Ematologia, A.O.U. di Udine
Study officials:
affiliation: Azienda Sanitaria Ospedaliera-Universitaria S. Giovanni Battista - TORINO
name: Umberto Vitolo, MD
role: STUDY_DIRECTOR
References:
citation: Boccomini C, Ladetto M, Rigacci L, Puccini B, Rattotti S, Volpetti S, Ferrero S, Chiarenza A, Freilone R, Novo M, Corradini P, Nassi L, Rusconi C, Stelitano C, Bolis S, Marina Liberati A, Tucci A, Baldini L, Balzarotti M, Evangelista A, Ciccone G, Vitolo U. A brief rituximab, bendamustine, mitoxantrone (R-BM) induction followed by rituximab consolidation in elderly patients with advanced follicular lymphoma: a phase II study by the Fondazione Italiana Linfomi (FIL). Br J Haematol. 2021 Apr;193(2):280-289. doi: 10.1111/bjh.17283. Epub 2021 Jan 21.