Comparison Between Local Radiotherapy Alone or Combined With Obinutuzumab in Early Stage Follicular Lymphoma: the GAZEBO Trial From the Fondazione Italiana Linfomi

NCT05929222 | Recruiting Phase 3

• 1 other identifier: FIL_GAZEBO
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 48

Brief Summary

Prospective, multicenter, open label, phase III randomized clinical trial in previously untreated Follicular Lymphoma in early stage. Patients will be randomized to receive Radiotherapy or Radiotherapy plus Obinutuzumab.

Conditions

Follicular Lymphoma

Keywords

Lymphoma; Follicular; Immunotherapy; FL; Radiotherapy; Early; Localized; Obinutuzumab; MRD; Minimal residual disease; PET

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Time between the randomization to first documentation of recurrence, progression or death from any cause at 2 years

  From treatment start up to 33 months (9 months treatment period and 24 months of follow-up)

Secondary Outcomes (14)

• Complete response rate (CRR)

  From therapy start up to end of treatment (9 months)

• Overall response rate (ORR)

  From therapy start up to end of treatment (9 months)

• Disease Free Survival (DFS)

  From post radiotherapy assessment up to 45 months (9 months treatment phase plus 36 months of follow-up)

• Event Free Survival (EFS)

  From therapy start up to 45 months (9 months treatment phase plus 36 months of follow-up)

• Number of patients with Molecular Response at end of treatment

  From therapy start up to end of treatment (9 months)

Study Arms (2)

Standard Arm

ACTIVE COMPARATOR

Radiotherapy alone

Radiation: Radiotherapy

Experimental Arm

EXPERIMENTAL

Radiotherapy plus Obinutuzumab

Other: Radiotherapy plus Obinutuzumab

Interventions

Radiotherapy RADIATION

Involved-Site Radiation Therapy 24Gy

Standard Arm

Radiotherapy plus Obinutuzumab OTHER

Involved-Site Radiation Therapy 24Gy followed by Obinutuzumab 1000mg flat dose 4 doses weekly plus addition 4 doses every 3 weeks

Experimental Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological documented diagnosis of Follicular Lymphoma grade I-IIIA as defined in the 2017 edition of World Health Organization (WHO)
• Ann Arbor Stage IA or IIA (includible in one radiation field), or IE, non-bulky (\<7 cm). Stage must be determined by PET/CT scan (Appendix 2)
• Patients performing PET before surgery can also be enrolled without repeating PET after surgery
• No previous treatment except for steroid pre-treatment
• FLIPI \< 2, FLIPI2 ≤ 2
• Age ≥ 18 years
• Negative bone marrow biopsy
• Qualitative/quantitative PCR centralized assessment of BCL2/IGH positive cells in peripheral blood (PB), bone marrow (BM).
• Centralized revision of the lymph node biopsy with FISH for t(14;18)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
• At least one site of measurable nodal disease pre-biopsy ≥ 2.0 cm in the longest transverse diameter as determined by CT scan or ultrasonography
• Adequate renal function defined as follows:
• Creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula)
• Adequate hepatic function per local laboratory reference range as follows:
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x UNL

You may not qualify if:

• Histological diagnosis of Follicular lymphoma grade IIIb
• Staging \>II or B symptoms or bulky disease (\> 7 cm)
• Stage II with distant involved sites, not includible in a single radiation field
• Primary cutaneous follicular lymphoma
• Known HIV positivity
• Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RNA on the same sample to confirm the result, if negative, the patient is eligible.
• Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a quantitative HBVDNA test will be performed and if positive the subject will be excluded. Patients with HBcAb positivity and negative HBV DNA should be prophylactically treated with oral Lamivudine (100 mg /day). Note: subjects with serologic evidence of prior vaccination to HBV (i.e., hepatitis B surface (HBs) antigen negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate
• Central Nervous System (CNS) involvement with lymphoma
• Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent
• Any history of other active malignancies within 3 years prior to study entry, except for adequately treated in situ carcinoma of the cervix uterine, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, previous malignancy confined and surgically resected with curative intent
• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
• Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
• Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment.
• If female, the patient is pregnant or breast-feeding
• Patients participating in other clinical studies.

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (48)

Azienda Ospedaliera Nazionale Ss Antonio E Biagio E C Arrigo, SCDU Ematologia

Alessandria, Italy

RECRUITING

AORN San Giuseppe Moscati Avellino, U.O.C. Ematologia e Trapianto Emopoietico

Avellino, Italy

RECRUITING

Centro Di Riferimento Oncologico Di Aviano, S.O.C. Oncologia Medica e dei Tumori Immunocorrelati

Aviano, Italy

RECRUITING

Istituto Tumori Bari Giovanni Paolo II, U.O. di Ematologia e Terapia Cellulare

Bari, Italy

RECRUITING

Ospedale degli Infermi di Biella, SSD Ematologia

Biella, Italy

RECRUITING

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia, U.O. Ematologia

Brescia, Italy

RECRUITING

ARNAS G. Brotzu, SC Ematologia e CTMO

Cagliari, Italy

NOT YET RECRUITING

Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS, Oncologia Medica

Candiolo, Italy

RECRUITING

Istituto Oncologico Veneto, U.O.C. Oncoematologia

Castelfranco Veneto, Italy

RECRUITING

Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco Di Catania, UOC Ematologia

Catania, Italy

NOT YET RECRUITING

Azienda Ospedaliera Santa Croce E Carle, S.C. di Ematologia

Cuneo, Italy

RECRUITING

Careggi University Hospital, SOD Ematologia

Florence, Italy

RECRUITING

Ssd Ematologia ASLTO4, S.S.D. Ematologia

Ivrea, Italy

NOT YET RECRUITING

Ospedale Santa Maria Goretti, SOD Ematologia

Latina, Italy

RECRUITING

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l., Oncoematologia

Meldola, Italy

RECRUITING

Azienda Ospedali Riuniti Papardo-Piemonte, U.O. Ematologia

Messina, Italy

RECRUITING

ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia

Milan, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale Dei Tumori, S.C. Ematologia e Trapianto Midollo Osseo Allogenico

Milan, Italy

RECRUITING

Ospedale San Raffaele S.r.l., Unitа Linfomi - Dipartimento Oncoematologia

Milan, Italy

RECRUITING

Azienda Ospedaliero Universitaria Di Modena, S.C. Ematologia

Modena, Italy

RECRUITING

Azienda Ospedaliera S Gerardo Di Monza, Ematologia

Monza, Italy

RECRUITING

Azienda Ospedaliera Universitaria Federico II Di Napoli, U.O.C. di Ematologia e Trapianti di Midollo

Naples, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Maggiore Della Carita, SCDU Ematologia

Novara, Italy

RECRUITING

Istituto Oncologico Veneto, UOC Oncologia 1

Padua, Italy

RECRUITING

Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello, Oncoematologia

Palermo, Italy

RECRUITING

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone, U.O.C. Ematologia

Palermo, Italy

NOT YET RECRUITING

Fondazione IRCCS Policlinico San Matteo, U.O.C. Ematologia I

Pavia, Italy

NOT YET RECRUITING

Hospital Santa Maria Della Misericordia, S.C. di Ematologia con TMO

Perugia, Italy

NOT YET RECRUITING

Azienda Unità Sanitaria Locale Di Piacenza, U.O.Ematologia

Piacenza, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana, U.O. Ematologia

Pisa, Italy

RECRUITING

Azienda Unita Sanitaria Locale Della Romagna, U.O.C. Ematologia

Ravenna, Italy

RECRUITING

Azienda USL IRCCS Di Reggio Emilia, S.C. Ematologia

Reggio Emilia, Italy

RECRUITING

Azienda Unita Sanitaria Locale Della Romagna, U.O. di Ematologia

Rimini, Italy

RECRUITING

ASL Roma 1, UOSD Ematologia

Roma, Italy

RECRUITING

Azienda Ospealiero Universitaria Policlinico Umberto I, Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione

Roma, Italy

RECRUITING

Azienda Ospedaliera S Giovanni Addolorata, UOC Ematologia

Roma, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Sant Andrea, UOC Ematologia

Roma, Italy

RECRUITING

Catholic University Of Sacred Heart, UOC Ematologia e Trapianto di cellule staminali emopoietiche

Roma, Italy

RECRUITING

Fondazione Policlinico Universitario Campus Bio-Medico, UOC di Ematologia e Trapianto di Cellule Staminali

Roma, Italy

RECRUITING

I.F.O. Istituti Fisioterapici Ospitalieri, UOSD Ematologia e Trapianto

Roma, Italy

RECRUITING

Ospedale Di Sassuolo S.p.A., U.O.S.D. di Oncologia

Sassuolo, Italy

RECRUITING

Azienda Ospedaliera Universitaria Senese, U.O.C. Ematologia

Siena, Italy

RECRUITING

Azienda Socio Sanitaria Territoriale Della Valtellina E Dell Alto Lario, Medicina Interna

Sondrio, Italy

RECRUITING

Azienda Ospedaliera S Maria Di Terni, S.C. Oncoematologia

Terni, Italy

NOT YET RECRUITING

Azienda Unita' Locale Socio Sanitaria N. 2 Marca Trevigiana, S.C di Ematologia

Treviso, Italy

RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale, SOC Clinica Ematologica

Udine, Italy

RECRUITING

Azienda Ospedaliera Ospedale Di Circolo E Fondazione Macchi, U.O.C Ematologia

Varese, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Integrata Verona, U.O.C. Ematologia

Verona, Italy

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma; Neoplasm, Residual

Interventions

Radiotherapy; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Alessandro Pulsoni, MD

  Ospedale Santa Maria Goretti Latina

  PRINCIPAL INVESTIGATOR

• Andrea Filippi, MD

  Università di Pavia-Fondazione IRCCS Policlinico San Matteo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Uffici Studi FIL

CONTACT

+390131033153; startup@filinf.it

Uffici Studi FIL

CONTACT

+390599769913; gestionestudi@filinf.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2023
• First Posted: July 3, 2023
• Study Start: December 14, 2023
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): April 1, 2031
• Last Updated: December 24, 2025

Record last verified: 2025-12

Locations

IT (48)