Study to Evaluate the Efficacy of Response-adapted Strategy in Follicular Lymphoma
A Multicenter, Phase III, Randomized Study to Evaluate the Efficacy of Response-adapted Strategy to Define Maintenance After Standard Chemoimmunotherapy in Patients With Advanced-stage Follicular Lymphoma.
1 other identifier
interventional
807
1 country
48
Brief Summary
Recently, the availability of R has substantially changed therapeutic approach to FL patients, since its combination with chemotherapy has improved response rates, progression free survival (PFS) and overall survival (OS). Based on the results of recently completed randomized studies the standard treatment for patients with FL should consist of an initial therapy with R-CHOP combination followed by two-year maintenance with R. Although results of randomized trials confirmed that this approach results in an improved patients' outcome and made a step forward in the management of patients with FL, one important question that can be raised is if this approach is really needed for all patients with FL or if some of them could benefit from a reduced intensity treatment achieving the same results in terms of outcome and survival . This question is of particular interest for newly diagnosed patients for whom maintenance does not affect OS. More recent data demonstrated that the outcome of patients with FL can be further predicted by evaluating the quality of response to therapy studying minimal residual disease (MRD). This project addresses the objective of evaluating if combining clinical response assessed on FDG-PET scan and molecular response measured through MRD detection could permit to single out groups of patients at different risk of progression and to consequently modulate maintenance therapies, with the aim to provide clinicians a more rational use of the available diagnostic and therapeutic resources.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2012
Longer than P75 for phase_3
48 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2012
CompletedFirst Submitted
Initial submission to the registry
November 21, 2013
CompletedFirst Posted
Study publicly available on registry
February 14, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2021
CompletedJune 21, 2022
June 1, 2022
9.4 years
November 21, 2013
June 16, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
PFS
To evaluate whether a FDG-PET and MRD response-based maintenance therapy is more effective in terms of Progression-Free Survival (PFS) than a standard maintenance therapy with Rituximab in patients with untreated, advanced, follicular lymphoma. Progression Free Survival (PFS) PFS will be measured from the date of randomization to the date of documented first occurrence of disease progression or relapse or to the date of death from any cause. Responding patients and patients who are lost to follow up will be censored at their last assessment date.
12/31/2019
Secondary Outcomes (6)
CRR
12/31/2019
ORR
12/31/2019
DR
12/31/2019
EFS
12/31/2019
OS
12/31/2019
- +1 more secondary outcomes
Study Arms (4)
GROUP 1 - STANDARD
OTHERR-CHOP or R-bendamustine + Standard Maintenance
GROUP 2
EXPERIMENTALFDG-PET POSITIVE (score 4-5) patients (High risk) R-CHOP or R-bendamustine + Ibritumomab Tiuxetan + Maintenance
GROUP 1a
EXPERIMENTALFDG-PET NEGATIVE (score 1-3) AND MRD NEGATIVE R-CHOP or R-bendamustine + Observation
GROUP 1b
EXPERIMENTALFDG-PET NEGATIVE (score 1-3) AND MRD POSITIVE R-CHOP or R-bendamustine + Maintenance weekly x4
Interventions
As induction therapy all patients will receive 6 courses of: Rituximab: 375 mg/m² day 1 iv Cyclophosphamide: 750 mg/m² day 1 iv Doxorubicin: 50 mg/m² day 1 iv Vincristine: 1.4 mg/m² day 1 iv (max dose 2mg) Prednisone: 100 mg day 1-5 os To allow administration of all drugs on the same day, Rituximab rapid infusion is permitted starting from cycle 2. Cycles are to be repeated every 21 days. or 6 courses of: Rituximab: 375 mg/m² day 1 iv Bendamustine: 90 mg/m² day 1 and 2 iv. To allow administration of all drugs on the same day, Rituximab rapid infusion is permitted starting from cycle 2. Cycles are to be repeated every 28 days.
Four weekly doses of Rituximab (375 mg/m²). Rituximab could be repeated for MRD positive for a maximum of three courses
single dose of (90)Y Ibritumomab Tiuxetan (0.4 mCi/kg). Following RIT patients will continue maintenance with Rituximab (375 mg/m² every 2 months) for a total of 11 infusions.
Rituximab 375 mg/m² every 2 months for 2 years. Maintenance will have to be started no more than 12 weeks after the last induction chemoimmunotherapy infusion.
Eligibility Criteria
You may qualify if:
- Histological diagnosis of B-Cell CD20+ Follicular Lymphoma (FL), grade I, II, IIIa according to the WHO 2008 classification
- ECOG performance status 0-2
- Age ≥ 18 years
- Ann Arbor stage II-IV
- FLIPI2\>0
- Presence of evaluable/measurable disease after diagnostic biopsy
- At least one of the following criteria for defining active disease:
- systemic symptoms
- cytopenia due to bone marrow involvement
- LDH\> upper normal value
- any nodal or extranodal tumor mass with a diameter \>7cm
- involvement of ≥ 3 nodal sites, each with a diameter of ≥ 3cm
- extranodal disease
- rapidly progressive disease
- Life expectancy \> 6 months
- +9 more criteria
You may not qualify if:
- Histological diagnosis of :
- any lymphoma other than follicular lymphoma and all CD20 negative B-cell lymphomas
- grade III b follicular lymphoma
- evidence of transformation to high grade lymphoma
- Ann Arbor stage I
- Suspect or clinical evidence of CNS involvement by lymphoma
- History of other malignancies within 5 years prior to study entry except for adequately treated carcinoma in situ of the cervix or 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
- Evidence of any severe active acute or chronic infection
- Concurrent co-morbid medical condition which might exclude administration of full dose chemotherapy
- Severe chronic obstructive pulmonary disease with hypoxemia
- Severe diabetes mellitus difficult to control with adequate insulin therapy
- Myocardial infarction within 6 months before study entry
- Clinically significant secondary cardiovascular disease e.g. uncontrolled hypertension, (resting diastolic blood pressure \>115 mmHg), uncontrolled multifocal cardiac arrhythmias, symptomatic angina pectoris or congestive cardiac failure NYHA class III-IV
- HbsAg-positive, HIV-positive, or HCVAb-positive patients
- Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (48)
Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Sede Di Meldola (Fc)
Meldola, Forlì Cesena, 47014, Italy
ASUR 8
Civitanova Marche, Macerata, 62012, Italy
Irccs Istituto Clinico Humanitas
Rozzano, Milano, 20089, Italy
Fondazione IRCCS Milano INT
Milan, MI, 20133, Italy
Azienda Ospedaliera S. Gerardo Di Monza
Monza, Monza Brianza, 20900, Italy
Irccs Centro Di Riferimento Oncologico Di Basilicata (Crob)
Rionero in Vulture, Potenza, 85028, Italy
P.O. Umberto I
Nocera Inferiore, Salerno, 84014, Italy
Fondazione Del Piemonte Per L'Oncologia Ircc Di Candiolo
Candiolo, Torino, 10060, Italy
A.O. S. Maria di Terni
Terni, TR, 05100, Italy
Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al)
Alessandria, 15121, Italy
A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona _
Ancona, 60126, Italy
A.O. Universitaria Ospedale Consorziale Policlinico Di Bari
Bari, 70124, Italy
A.O. Ospedale Degli Infermi
Biella, 13900, Italy
A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
Bologna, 40138, Italy
Pres.Ospedal.Spedali Civili Brescia
Brescia, 25125, Italy
Stabilimento "Perrino" - Brindisi -
Brindisi, 72100, Italy
Ospedale Armando Businco - Cagliari
Cagliari, 09121, Italy
A.O. Universitaria Ospedale Vittorio Emanuele Di Catania
Catania, 95124, Italy
Azienda Ospedaliera S. Croce E Carle Di Cuneo
Cuneo, 12100, Italy
A.O. Universitaria Careggi Di Firenze
Florence, 50139, Italy
A.O. Universitaria S. Martino Di Genova
Genova, 16132, Italy
Ematologia Ospedale Vito Fazzi
Lecce, Italy
Presidio Ospedaliero - Matera -
Matera, 75100, Italy
Azienda Ospedaliera Papardo
Messina, 98158, Italy
Irccs Ospedale Maggiore Policlinico Di Milano
Milan, 20122, Italy
Ospedale Ca' Granda-Niguarda
Milan, 20162, Italy
A.O. Universitaria Policlinico Di Modena
Modena, 41124, Italy
Irccs Istituto Nazionale Tumori Fondazione Pascale
Napoli, Italy
A.O. Universitaria Maggiore Della Carita' Di Novara
Novara, 28100, Italy
Ospedale San Francesco
Nuoro, 08100, Italy
A.O. Universitaria Policlinico Giaccone Di Palermo
Palermo, 90127, Italy
A.O. "V. Cervello"
Palermo, 90146, Italy
A O Universitaria di Parma
Parma, Italy
IRCCS Policlinico S. Matteo
Pavia, 27100, Italy
Azienda Ospedaliera Di Perugia - Ospedale S. Maria Della Misericordia -
Perugia, 06134, Italy
Ospedale Civile Spirito Santo
Pescara, 65124, Italy
Ausl Di Piacenza
Piacenza, 29121, Italy
A.O. Universitaria Pisana
Pisa, 56126, Italy
Ospedale Bianchi - Melacrino - Morelli
Reggio Calabria, 89123, Italy
Ausl Di Rimini
Rimini, 47924, Italy
Universita' Degli Studi Di Roma 'La Sapienza'
Roma, 00185, Italy
Casa sollievo della Sofferenza
San Giovanni Rotondo, Italy
A.O. Universitaria Senese
Siena, 53100, Italy
A.O. Universitaria S. Giovanni Battista-Molinette Di Torino
Torino, 10126, Italy
Ospedale Ca Foncello
Treviso, Italy
A.O.Cardinale Panico Ematologia e centro trapianti
Tricase (LE), Italy
A.O. Universitaria S. Maria Della Misericordia Di Udine
Udine, 33100, Italy
Ospedale Di Circolo E Fondazione Macchi
Varese, 21100, Italy
Related Publications (2)
Durmo R, Chauvie S, Fallanca F, Bergesio F, Pinto A, Del Giudice I, Coscia M, Corradini P, Angelucci E, Tosi P, Freilone R, Ballerini F, Bari A, Pastore D, Zinzani PL, Bolis S, Flenghi L, Liso A, Olivieri J, Marcheselli L, Merli M, Versari A, Guerra L, Luminari S. Prognostic role of interim PET in follicular lymphoma: a post hoc study of FOLL12 trial by Fondazione Italiana Linfomi. Blood Adv. 2025 Jun 24;9(12):2927-2934. doi: 10.1182/bloodadvances.2024014790.
PMID: 40106688DERIVEDLuminari S, Manni M, Galimberti S, Versari A, Tucci A, Boccomini C, Farina L, Olivieri J, Marcheselli L, Guerra L, Ferrero S, Arcaini L, Cavallo F, Kovalchuk S, Skrypets T, Del Giudice I, Chauvie S, Patti C, Stelitano C, Ricci F, Pinto A, Margiotta Casaluci G, Zilioli VR, Merli A, Ladetto M, Bolis S, Pavone V, Chiarenza A, Arcari A, Anastasia A, Dondi A, Mannina D, Federico M; Fondazione Italiana Linfomi. Response-Adapted Postinduction Strategy in Patients With Advanced-Stage Follicular Lymphoma: The FOLL12 Study. J Clin Oncol. 2022 Mar 1;40(7):729-739. doi: 10.1200/JCO.21.01234. Epub 2021 Oct 28.
PMID: 34709880DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Donato Mannina, MD
Hematology, Azienda Ospedali Riuniti Papardo-Piemonte, Messina, Italy.
- PRINCIPAL INVESTIGATOR
Massimo Federico, MD
Department of Diagnostic Medicine, Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Modena , Italy
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 21, 2013
First Posted
February 14, 2014
Study Start
July 1, 2012
Primary Completion
December 1, 2021
Study Completion
December 1, 2021
Last Updated
June 21, 2022
Record last verified: 2022-06