Clinical trial NCT00774826: Multicentric Study, Three Randomized Arms (R-CVP vs R-CHOP vs R-FM),for Patients With Stage II-IV Follicular Lymphoma
Official title: Phase III Multicentric IIL Study, Three Randomized Arms (R-CVP vs R-CHOP vs R-FM),for Treatment of Patients With Stage II-IV Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Follicular Lymphoma
Keywords: Follicular lymphoma
Rituximab
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2008-10-17
Enrollment: 534
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to define an improvement and theassessment of the Time to Treatment Failure in patients randomized in three different arms:

R-CVP vs R-CHOP vs R-FM.

Detailed description: Assessment of Overall Survival (OS)in patients treated with R-CVP, R-CHOP and R-FM. -Assessment of Progression Free Survival (PFS)in patients treated with R-CVP, R-CHOP - Assessment of Duration of Response (DR)in patients treated with R-CVP, R-CHOP and R-FM. - Assessment of Response Rate(RR) in patients treated with R-CVP, R-CHOP and R-FM. - Assessment of molecular Response Rate in patients treated with R-CVP, R-CHOP and R-FM. - Assessment of toxicity of R-CVP, R-CHOP, R-FM treatments.

Eligibility criteria: Inclusion Criteria:

1. Histological DIAGNOSIS of B cell follicular lymphoma
2. ECOG performance status 0-2
3. Age range 18-75
4. Ann Arbor Stage: II-IV
5. Assessment of pathology with diagnostics biopsy
6. Presence of one of these criteria:

   * B Sistemic symptoms B
   * Extranodale pathology
   * Cytopenia
   * Splenomegaly
   * Leukemia
   * Serous effusion
   * Ves \> 20 mm/h
   * Ldh \> normal value
   * Nodale or extranodal mass \> 7 cm
   * 3 or more nodal sites \> 3 cm
   * Adenopatic syndrome
7. LVEF \> 50%
8. Normal hepatic (bilirubin \< 1.5 mg/dl) and renal functionality (creatinin \< 2 mg/dl). If there is a lymphoma it's allow values of bilirubin \> 1.5 mg/dl and of creatinin \> 2mg/dl
9. No previous treatment for follicolar lymphoma unless RT-IF
10. Lifetime \> 6 mounth
11. Absence of HbsAg, HCV e HIV
12. Negative Coombs Test
13. Negative pregnant test
14. Cotracceptive method during the treatment and the follow three months
15. Formal written consent
16. Ability to follow the patients after the treatment for follow up

Exclusion Criteria:

1. Histological Diagnosis of all type of lymphoma unless Follicularlymphoma, CD20 lymphoma, stage IIIb of follicular lymphoma and high degree lymphoma
2. Stage I of Ann Arbor scale
3. Central Nervous system involvement
4. HIV, HBV OR HCV Positivity
5. Cardiac Pathology
6. Positive Coombs Test
7. Previous chemotherapeutic treatment
8. Hypersensitivity to antibodyes or other murine proteins
9. Previous cancer pathology unless in situ cervix and epithelial carcinomas
10. Other type of infections
11. Pregnant and nursing woman

Primary outcomes:
measure: Assessment of the Time to Treatment Failure (TTF)in patients treated with R-CVP, R-CHOP and R-FM.
timeFrame: 2 years
Secondary outcomes:
measure: Assessment of Overall Survival (OS)in patients treated with R-CVP, R-CHOP and R-FM. -
timeFrame: 3 years
measure: Assessment of Progression Free Survival (PFS)in patients treated with R-CVP, R-CHOP
timeFrame: 2 years
measure: Assessment of Duration of Response (DR)in patients treated with R-CVP, R-CHOP and R-FM.
timeFrame: 2 years
measure: Assessment of Response Rate(RR) in patients treated with R-CVP, R-CHOP and R-FM.
timeFrame: 2 years
measure: Assessment of molecular Response Rate in patients treated with R-CVP, R-CHOP and R-FM.
timeFrame: 2 years
measure: Assessment of toxicity of R-CVP, R-CHOP, R-FM treatments.
timeFrame: 2 years
Other outcomes:
Locations:
city: Acquaviva delle fonti (BA)
country: Italy
facility: Ente ecclesiastico Ospedale generale regionale Miulli
city: Alessandria
country: Italy
facility: Az.Ospedaliera SS.Antonio, Biagio e Cesare Arrigo-U.O.A.Ematologia
city: Asti
country: Italy
facility: Presidio Ospedaliero C.Massaia di Asti
city: Aviano
country: Italy
facility: Istituto Nazionale Tumori
city: Bari
country: Italy
facility: IRCCS Istituto tumori Giovanni Paolo II
city: Biella
country: Italy
facility: Divisione Medicina B Ospedale degli Infermi
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola - Istituto di Ematologia e Oncologia medica L.e A. Seragnoli
city: Bolzano
country: Italy
facility: Ospedale di Bolzano Divisione di Ematologia e Centro Trapianti di Midollo Osseo
city: Brescia
country: Italy
facility: A.O.Spedali civili di Brescia
city: Brindisi
country: Italy
facility: Presidio Ospedaliero A.Perrino
city: Cagliari
country: Italy
facility: Ospedale Businco, Divisione di Ematologia
city: Camposanpiero (PD)
country: Italy
facility: Ospedale Civile
city: Candiolo (TO)
country: Italy
facility: Istituto per la ricerca e la cura del cancro
city: Carpi (MO)
country: Italy
facility: A.O. dell'Annunziata Unita' Operativa di Ematologia
city: Carpi (Mo)
country: Italy
facility: Ospedale Ramazzini Day Hospital Oncologico
city: Catania
country: Italy
facility: Ospedale Garibaldi-Nesima
city: Catania
country: Italy
facility: Universita' degli studi di Catania
city: Catanzaro
country: Italy
facility: A.O. Pugliese A. Ciaccio
city: Catanzaro
country: Italy
facility: A.O.Pugliese Ciaccio Diviisone di Ematologia
city: Chivasso (TO)
country: Italy
facility: Ospedale civico di Chivasso
city: Ciriè (TO)
country: Italy
facility: Ospedale di Ciriè U.O.N.A. Oncologia servizio di Ematologia
city: Civitanova Marche (MC)
country: Italy
facility: Ospedale civile Divisione di Ematologia
city: Correggio (RE)
country: Italy
facility: Ospedale San Sebastiano
city: Cosenza
country: Italy
facility: Presidio Ospedaliero Annunziata
city: Cremona
country: Italy
facility: Azienda istituti ospedalieri di Cremona
city: Firenze
country: Italy
facility: Policlinico Careggi, cattedra e diviisone di Ematologia
city: Genova
country: Italy
facility: E.O.Ospedali Galliera U.O.Ematologia
city: Genova
country: Italy
facility: Ospedale San Martino - Divisione di Ematologia
city: La Spezia
country: Italy
facility: Ospedale Felettino reparto di Oncologia
city: Lecce
country: Italy
facility: Ospedale Vito Fazzi
city: Lecco
country: Italy
facility: Ospedale A.Manzoni Oncologia medica
city: Matera
country: Italy
facility: Ospedale Madonna delle grazie U.O. Ematologia
city: Messina
country: Italy
facility: Azienda Ospedaliera Papardo
city: Messina
country: Italy
facility: Policlinico universitario U.O. Ematologia
city: Milano
country: Italy
facility: Azienda Ospedaliera Fatebenefratelli e Oftalmico
city: Milano
country: Italy
facility: IRCCS San Raffaele Unità di Chemioterapia
city: Milano
country: Italy
facility: Osp. San Carlo Borromeo Divisione di Oncologia Medica
city: Milano
country: Italy
facility: Ospedale Maggiore IRCCS-Dipartimento di Ematologia
city: Milano
country: Italy
facility: Ospedale Niguarda CA' Granda
city: Milano
country: Italy
facility: Ospedale San Paolo U.O. Oncologia Medica
city: Modena
country: Italy
facility: Policlinico di Modena - Università degli studi
city: Monza (MI)
country: Italy
facility: Ospedale S. Gerardo Divisione di ematologia
city: Napoli
country: Italy
facility: AORN Cardarelli U.O.Ematologia
city: Noale
country: Italy
facility: Ospedale P.F.Calvi dipartimento id Oncologia ed Ematologia
city: Nocera Inferiore
country: Italy
facility: Presidio Ospedaliero Umberto I Medicina ed Onco-Ematologia
city: Novara
country: Italy
facility: A.O. Maggiore della Carità S.C.D.U. Ematologia
city: Padova
country: Italy
facility: A.O. di Padova Divisione di Oncologia Medica
city: Palermo
country: Italy
facility: Casa di cura La Maddalena Unita' di Ematologia
city: Palermo
country: Italy
facility: Policlinico P.Giaccone
city: Parma
country: Italy
facility: Universita' degli studi di Parma
city: Pavia
country: Italy
facility: Policlinico San Matteo - Medicina generale
city: Pavia
country: Italy
facility: Policlinico San Matteo
city: Perugia
country: Italy
facility: Policlinico Monteluce Divisione di Ematologia
city: Pescara
country: Italy
facility: Ospedale Santo Spirito Dipartimento di Ematologia
city: Pescara
country: Italy
facility: Ospedale Santo Spirito-Dipartimento di Oncologia
city: Piacenza
country: Italy
facility: Ospedale Civile, Sezione di Ematologia
city: Pisa
country: Italy
facility: Ospedale S. Chiara Azienda ospedaliera pisana
city: Reggio Calabria
country: Italy
facility: Presidio Ospedali riuniti "Bianchi, Melacrino, Morelli" Divisione di ematologia
city: Reggio Emilia
country: Italy
facility: Azienda ospedaliera Arcispedale S.Maria Nuova
city: Rionero in Vulture (PZ)
country: Italy
facility: Ospedale Oncologico regionale CROB
city: Roma
country: Italy
facility: A.O.S.Andrea Reparto di Ematologia e Immunoematologia
city: Roma
country: Italy
facility: Azienda Policlinico Umberto I - La Sapienza
city: Roma
country: Italy
facility: Istituto Regina Elena
city: Roma
country: Italy
facility: Ospedale San Giacomo U.O. Ematologia
city: Roma
country: Italy
facility: Policlinico A. Gemelli Università Cattolica del Sacro Cuore
city: Roma
country: Italy
facility: Policlinico Universitario Campus biomedico
city: Roma
country: Italy
facility: Policlinico Universitario Tor Vergata
city: Roma
country: Italy
facility: Universita' La Sapienza
city: Ronciglione (VT)
country: Italy
facility: P.O. Roncilgione U.O. Ematologia
city: Rozzano (MI)
country: Italy
facility: Istituto clinco Humanitas
city: San Giovanni Rotondo (FG)
country: Italy
facility: IRCCS Casa Sollievo della Sofferenza
city: Sassari
country: Italy
facility: Istituto di Ematologia Università degli studi di Sassari
city: Sassuolo (MO)
country: Italy
facility: Ospedale civile DH oncologico
city: Savona
country: Italy
facility: Ospedale San Paolo
city: Sondalo
country: Italy
facility: A.O. della Valtellina e della Valchiavenna Presidio Ospedaliero di Sondalo
city: Terni
country: Italy
facility: Azienda Ospedaliera S. Maria
city: Terni
country: Italy
facility: Ospedale S. Maria Clinica Medica Servizio Oncologico
city: Torino
country: Italy
facility: A.O.San Giovanni Battista
city: Tricase (LE)
country: Italy
facility: A.O.Cardinale Panico Ematologia e centro trapianti
city: Trieste
country: Italy
facility: Azienda Ospedaliera Ospedali riuniti di Trieste
city: Varese
country: Italy
facility: Ospedale di circolo e Fondazione Macchi
city: Venezia
country: Italy
facility: O.C.SS. Giovanni e Paolo - U.O. Ematologia
Study officials:
affiliation: Azienda Ospedaliero-Universitaria di Modena
name: Massimo Federico, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-Term Results of the FOLL05 Trial Comparing R-CVP Versus R-CHOP Versus R-FM for the Initial Treatment of Patients With Advanced-Stage Symptomatic Follicular Lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. doi: 10.1200/JCO.2017.74.1652. Epub 2017 Nov 2.
citation: Rossi D, Bruscaggin A, La Cava P, Galimberti S, Ciabatti E, Luminari S, Rigacci L, Tucci A, Pulsoni A, Bertoldero G, Vallisa D, Rusconi C, Spina M, Arcaini L, Angrilli F, Stelitano C, Merli F, Gaidano G, Federico M, Palumbo GA. The genotype of MLH1 identifies a subgroup of follicular lymphoma patients who do not benefit from doxorubicin: FIL-FOLL study. Haematologica. 2015 Apr;100(4):517-24. doi: 10.3324/haematol.2014.108183. Epub 2015 Jan 16.