Clinical trial NCT01250223: Study of Prognosis of Follicular Lymphoma Through a Prospective Collection of Data (F2-study)
Official title: F2-PROTOCOL: Prospective Collection of Data of Possible Prognostic Relevance in Patients With Follicular Lymphoma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lymphoma, Follicular
Keywords: Lymphoma, Follicular
Prognosis
Progression-Free Survival
Outcome
International Cooperation
Data Collection
Prospective studies
Rare Diseases
Lead sponsor: Associazione Angela Serra per la ricerca sul cancro
Sponsor class: OTHER
Collaborators: name: Fondazione Italiana Linfomi - ETS
name: The International Non-Hodgkin Lymphoma Prognostic Factor Project
First posted: 2010-11-30
Enrollment: 1093
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Previously-untreated patients with de novo diagnosis of Follicular Lymphoma according to World Health Organization (WHO) classification (grade 1,2,3a,3b)

Brief summary: The F2-study is a complement of the previous studies of the Follicular Lymphoma Prognostic Factors Project which permitted the development of the Follicular Lymphoma International Prognostic Index (FLIPI).

The F2-study is designed as a prospective collection of information potentially useful to predict the prognosis of newly diagnosed Follicular Lymphoma patients, and its purposes are to validate the FLIPI and to verify whether a prognostic collection of data would allow the development of a more accurate prognostic index.

Detailed description: So far, in patients with lymphoma a variety of studies aimed at the evaluation of prognosis have been conducted. In particular, different demographic, clinical and biological factors have shown a prognostic role in univariate and multivariate analysis, including age, gender, stage, tumor burden, bone marrow involvement, systemic symptoms, Performance status, serum lactate dehydrogenase (LDH) level, anemia, erythrocyte sedimentation rate (ESR) and beta-2 microglobulin.

The combination of those parameters has allowed the identification of several prognostic scores.

Attempts to define prognosis in follicular lymphomas begun in the late '70s. Then, when in 1993 the International Prognostic Index (IPI) was defined for aggressive lymphomas it was also applied to low-grade lymphomas leading to conflicting results, and the need for a prognostic index specifically designed for follicular lymphomas emerged.

A large study on prognosis in patients with follicular lymphoma was performed by the Italian Lymphoma Intergroup that leaded to the definition of the Italian Lymphoma Intergroup (ILI) score, based on 987 patients (Federico M et al. Blood 2000; 95(3):783-789). In 2004 the Follicular Lymphoma International Prognostic Project allowed the definition of a new score on 4167 pts with follicular lymphoma, the Follicular Lymphoma International Prognostic Index (FLIPI) (Solal-Céligny P et al. Blood 2004;104(5):1258-1265). This score is based on the evaluation of age (younger than 60 years vs 60 years or older), Ann Arbor stage (I-II vs III-IV), number of nodal sites (0-4 vs \> 5 or more), Hemoglobin (Hb)level (greater than or equal 12g/dL vs lower than 12g/dL), serum Lactate Dehydrogenase (LDH) (normal vs elevated) and identifies three main groups of patients with different survival:low risk (0-1 factors); intermediate risk (2 factors); high risk (3-5 factors).

Notwithstanding the huge number of patients considered in these studies, all mentioned prognostic scores (IPI, ILI and FLIPI) are based on a retrospective analysis of archive data. This approach can introduce biases that can hamper final results. A first problem is the selection of patients that can be influenced by single institution policy and patient's or physician's related factors. Furthermore, some important variables, such as beta2-microglobulin or Erythrocyte Sedimentation Rate (ESR), that have frequently shown a high prognostic significance in univariate analysis, are hardly included in the final indexes because they are available only in a small number of patients thus loosing their value in multivariate analysis. Then, lacking homogeneous and prospectively defined criteria, retrospective evaluation of some study parameter as for example clinical response cannot be easily defined and all derived endpoints such as Failure Free Survival (FFS)or Progression Free Survival (PFS) may be biased.

Finally the results of a retrospective analysis aiming at the evaluation of survival are dependent on the type of administered treatment and with the recent advent of new drugs such as monoclonal antibodies and purine analogs that can be used also in the elderly patients the role of some established prognostic factor may have changed.

These are the reasons why we thought it would be useful to start a new study based on the prospective registration in a short period of time of patients with follicular lymphoma for whom it would be possible collect an exhaustive set of clinical data and biological information.

Eligibility criteria: Inclusion Criteria:

* Patients with newly diagnosed follicular lymphoma
* Patients with histologically confirmed diagnosis of follicular lymphoma according to WHO classification (any grade)
* Age over 18
* Written informed consent

Exclusion Criteria:

* None

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 5-year
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 5-year
measure: Event Free Survival (EFS)
timeFrame: 5-year
measure: Treatment Free Survival
timeFrame: 5-year
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine - Department of Hematology/Oncology
state: Illinois
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Buenos Aires
country: Argentina
facility: Academia Nacional de Medicina - Oncohematology Department, Instituto de Investigaciones Hematologicas
city: Buenos Aires
country: Argentina
facility: Centro de Internacion e Investigacion Clinica "Angelica Ocampo" - Hematologia
city: Praha
country: Czechia
facility: Charles University General Hospital - Ist Dept Medicine
city: Besancon
country: France
facility: Centre Hospitalier Universitaire - Hématologie
city: Bordeaux
country: France
facility: Institut Bergonié Comprehensive Cancer Center
city: Le Mans
country: France
facility: Centre Jean Bernard, Clinique Victor Hugo
city: Nantes
country: France
facility: Centre Hospitalier Univeristaire - Hématologie clinique
city: Nimes
country: France
facility: Hopital caremeau - Service de Medecine Interne B
city: Tours
country: France
facility: CHRU Bretonneau - Oncologie medicale
city: Brescia
country: Italy
facility: Presidio Spedali Civili
state: BS
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S. Croce e Carle
state: CN
city: Catania
country: Italy
facility: Azienda O.U. Vittorio Emanuele-Ferrarotto-S. Bambino
state: CT
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Pugliese-Ciaccio
state: CZ
city: San Giovanni Rotondo
country: Italy
facility: Ospedale Casa Sollievo della Sofferenza IRCCS
state: FG
city: Lido di Camaiore
country: Italy
facility: Ospedale unico Versilia USL 12 - Divisione di Medicina II, DH Oncoematologico
state: Lucca
city: Taormina
country: Italy
facility: Ospedale San Vincenzo - Ematologia e Immunologia
state: Messina
city: Messina
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Papardo-Piemonte
state: ME
city: Milano
country: Italy
facility: Istituto Clinico Humanitas
state: MI
city: Milano
country: Italy
facility: Istituto Scientifico Universitario San Raffaele
state: MI
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: MI
city: Matera
country: Italy
facility: Ospedale Madonna delle Grazie
state: Mount
city: Modena
country: Italy
facility: Dipartimento di Oncologia, Ematologia e Patologie dell'Apparato Respiratorio, Univ. di Modena e Reggio Emilia - Ematologia
state: MO
city: Modena
country: Italy
facility: Dipartimento di Oncologia, Ematologia e Patologie dell'Apparato Respiratorio, Univ. di Modena e Reggio Emilia - Medicina Interna
state: MO
city: Modena
country: Italy
facility: Dipartimento di Oncologia, Ematologia e Patologie dell'Apparato Respiratorio, Univ. di Modena e Reggio Emilia - Oncologia II
state: MO
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena
state: Pa
city: Piacenza
country: Italy
facility: Ospedale civile Guglielmo da Saliceto - Medicina Oncologica ed Ematologica
state: PC
city: Pescara
country: Italy
facility: Ospedale Santo Spirito, USL di Pescara - Dipartimento di Oncologia
state: PE
city: Perugia
country: Italy
facility: Policlinico Monteluce - Divisione di Clinica Medica
state: PG
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana - UO di Ematologia
state: PI
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo - Clinica Ematologica
state: PV
city: Potenza
country: Italy
facility: Azienda Ospedaliera S. Carlo - Oncologia Medica
state: PZ
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera Bianchi-Melacrino-Morelli
state: RC
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova
state: RE
city: Sondalo
country: Italy
facility: Ospedale E. Morelli - Divisione di Medicina Generale, Ematologia
state: Sondrio
city: Torino
country: Italy
facility: Azienda Ospedaliera Universitaria San Giovanni Battista
state: TO
city: Udine
country: Italy
facility: Policlinico Universitario a gestione diretta - Divisione di Ematologia
state: UD
city: Venezia
country: Italy
facility: Ospedale Civile SS. Giovanni e Paolo - UO di Ematologia
state: VE
city: Novara
country: Italy
facility: Azienda Ospedaliera Maggiore della Carità
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea - UOC Ematologia
city: Roma
country: Italy
facility: Ospedale Sant'Eugenio - Ematologia
city: Roma
country: Italy
facility: Università la Sapienza, Dip. di Biotecnologie Cellulari ed Ematologia, Sez. Ematologia
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol - Institut Català d'Oncologia
city: Barcelona
country: Spain
facility: Hospital Clinic - Institut d'Hematologia i Oncologia
city: Barcelona
country: Spain
facility: Hospital Universitario Vall de Hebron - Servei d'Hematologia Clinica
city: Girona
country: Spain
facility: Institu Catala d'Oncologia - Servei d'Hematologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario
city: Bellinzona
country: Switzerland
facility: Ospedale S. Giovanni
state: TI
city: London
country: United Kingdom
facility: Barths and The London NHS Trust
Study officials:
affiliation: Dip. Oncologia, Ematologia e Patologie dell'Apparato Respiratorio - Università di Modena e Reggio Emilia, Modena, Italy
name: Massimo Federico, MD
role: STUDY_CHAIR
affiliation: Centre Jean Bernard, Le Mans, France
name: Philippe Solal-Céligny, MD
role: STUDY_CHAIR
affiliation: Institut d'Hematologia i Oncologia, Hospital Clinic, Barcelona, Spain
name: Armando Lopez-Guillermo, MD
role: STUDY_CHAIR
affiliation: UT MD Anderson Cancer Ctr, Houston, TX, USA
name: Peter McLaughlin, MD
role: STUDY_CHAIR
affiliation: Azienda Universitaria Ospedaliera San Giovanni Battista, Torino, Italy
name: Umberto Vitolo, MD
role: STUDY_CHAIR
affiliation: Instituto Seragnoli, Unità Operativa di Emolinfopatologia, Università di Bologna, Bologna, Italy
name: Stefano A. Pileri, MD
role: STUDY_CHAIR
References:
citation: Federico M, Bellei M, Pro B, Lopez-Guillermo A, Marcheselli L, Trneny M, Soubeyran P, MCLaughlin P, Pileri S, Solal-Céligny P on behalf of the F2 study. Revalidation of FLIPI in patients with Follicular Lymphoma (FL) registered in the F2 study and treated upfront with immunochemotherapy. J Clin Oncol 25(18s), 2007. Abstr 8008.
citation: Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, Pro B, Martelli M, Soubeyran P, Cortelazzo S, Martinelli G, Pileri S, McLaughlin P, Solal-Céligny P on behalf of International Follicular Lymphoma Prognostic factor Project (IFLPFP) F2-study group. F2 prognostic index. Ann Oncol 19(suppl 4):101-102, 2008. Abstr 058.
citation: Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, Pro B, Pileri S, Pulsoni A, Soubeyran P, Cortelazzo S, Martinelli G, Martelli M, Rigacci L, Arcaini L, Di Raimondo F, Merli F, Sabattini E, McLaughlin P, Solal-Celigny P. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol. 2009 Sep 20;27(27):4555-62. doi: 10.1200/JCO.2008.21.3991. Epub 2009 Aug 3.
citation: Solal-Celigny P, Bellei M, Marcheselli L, Pesce EA, Pileri S, McLaughlin P, Luminari S, Pro B, Montoto S, Ferreri AJ, Deconinck E, Milpied N, Gordon LI, Federico M. Watchful waiting in low-tumor burden follicular lymphoma in the rituximab era: results of an F2-study database. J Clin Oncol. 2012 Nov 1;30(31):3848-53. doi: 10.1200/JCO.2010.33.4474. Epub 2012 Sep 24.