Shortened vs Standard Chemotherapy Combined With Immunotherapy for the Initial Treatment of Patients With High Tumor Burden Follicular Lymphoma

Summary

FIL\_FOLL19 is an open-label, multicenter, randomized phase III trial. The sponsor of this clinical trial is Fondazione Italiana Linfomi (FIL).

The Primary Objective of the study is to demonstrate that, in patients with newly diagnosed, advanced stage Follicular Lymphoma (FL) with high tumor burden according to the Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria, a treatment strategy that reduces the number of chemotherapy cycles in case of early response to immunochemotherapy is not inferior compared to standard therapy at full dose in terms of Progression-Free Survival (PFS).

Conditions

• Follicular Lymphoma

Interventions

DRUG

Immunochemotherapy regimen: Rituximab-bendamustine (Arm A)

Arm A (Standard arm): 4 cycles of Rituximab-bendamustine Q28 (28-days cycles); Patients will undergo an early restaging after cycle 4: those with at least a stable disease will complete the induction treatment with 2 cycles of R-bendamustine Q28 + 2 cycles Q28 of rituximab; Both Arms: Whichever the regimen, in responding patients (Complete Remission CR, Partial Remission PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 Monoclonal Antibody (MoAb) used for induction. Patients in both arms with progressive disease at any time and patients in stable disease (SD) at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

DRUG

Immunochemotherapy regimen: Rituximab-bendamustine (Arm B)

Arm B (Experimental arm): 4 cycles of Rituximab-bendamustine Q28 (28-days cycles); After cycle 4 patients will undergo an early restaging. Induction therapy shall be completed based on the response achieved and on the treatment chosen as below specified: * if in CR: patients will receive no more chemotherapy but will complete induction with the MoAb only, in this case: 4 cycles of rituximab; * if less than CR (PR, SD): the immunochemotherapy program will be completed as outlined for Arm A: 2 cycles of R-bendamustine Q28 + 2 cycles Q28 of rituximab; Both Arms: Whichever the regimen, in responding patients (CR, PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 Monoclonal Antibody (MoAb) used for induction. Patients in both arms with progressive disease at any time and patients in SD at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

DRUG

Immunochemotherapy regimen: R-CHOP (Arm A)

Arm A (Standard arm): 4 cycles of R-CHOP Q21 (21-days cycles); R-CHOP = Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone Patients will undergo an early restaging after cycle 4: those with at least a stable disease will complete the induction treatment with 2 cycles of R-CHOP Q21 + 2 cycles Q21 of rituximab; Both Arms: Whichever the regimen, in responding patients (Complete Remission CR, Partial Remission PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 Monoclonal Antibody (MoAb) used for induction. Patients in both arms with progressive disease at any time and patients in stable disease (SD) at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion: these patients will be included in the analysis planned by the study.

DRUG

Immunochemotherapy regimen: R-CHOP (Arm B)

Arm B (Experimental arm): 4 cycles of R-CHOP Q21 (21-days cycles); R-CHOP = Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone After cycle 4 patients will undergo an early restaging: induction therapy shall be completed based on the response achieved and on the treatment chosen: * if in CR: patients will receive no more chemotherapy but will complete induction with the MoAb only, in this case: 4 cycles of rituximab; * if less than CR (PR, SD): the immunochemotherapy program will be completed as outlined for Arm A: 2 cycles of R-CHOP Q21+ 2 cycles Q21of rituximab Both Arms: in responding patients (CR, PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 MoAb used for induction. Patients in both arms with progressive disease at any time and patients in SD at the EOI shall be considered for salvage therapy at clinician discretion: these patients will be included in the analysis.

DRUG

Immunochemotherapy regimen: G-bendamustine (Arm A)

Arm A (Standard arm): 4 cycles of G-bendamustine Q28 (28-days cycles); G-Bendamustine = Obinutuzumab and Bendamustine Patients will undergo an early restaging after cycle 4: those with at least a stable disease will complete the induction treatment with 2 cycles of G-bendamustine Q28 (28-days cycles); Both Arms: Whichever the regimen, in responding patients (Complete Remission CR, Partial Remission) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 Monoclonal Antibody (MoAb) used for induction. Patients in both arms with progressive disease at any time and patients in Stable Disease SD at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

DRUG

Immunochemotherapy regimen: G-bendamustine (Arm B)

Arm B (Experimental arm): 4 cycles of G-bendamustine Q28 (28-days cycles); G-Bendamustine = Obinutuzumab and Bendamustine After cycle 4 patients will undergo an early restaging. Induction therapy shall be completed based on the response achieved and on the treatment chosen as below specified: * if in CR: patients will receive no more chemotherapy but will complete induction with the Monoclonal Antibody (MoAb) only, in this case 2 cycles of obinutuzumab; * if less than CR (PR, SD): the immunochemotherapy program will be completed as outlined for Arm A: 2 cycles of G-bendamustine Q28; Both Arms: in responding patients (CR, PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 (MoAb) used for induction. Patients in both arms with progressive disease at any time and patients in SD at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

DRUG

Immunochemotherapy regimen: G-CHOP (Arm A)

Arm A (Standard arm): 4 cycles of G-CHOP Q21 (21-days cycles) G-CHOP = Obinutuzumab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone Patients will undergo an early restaging after cycle 4: those with at least a stable disease will complete the induction treatment with 2 cycles of G-CHOP Q21 + 2 cycles Q21 of obinutuzumab; Both Arms: Whichever the regimen, in responding patients (Complete Remission CR, Partial Remission PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 Monoclonal Antibody (MoAb) used for induction. Patients in both arms with progressive disease at any time and patients in stable disease (SD) at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

DRUG

Immunochemotherapy regimen: G-CHOP (Arm B)

4 cycles of G-CHOP Q21 (21-days cycles) G-CHOP = Obinutuzumab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone After cycle 4 patients will undergo an early restaging. Induction therapy shall be completed based on the response achieved and on the treatment chosen as below specified: * if in CR: patients will receive no more chemotherapy but will complete induction with the Monoclonal Antibody (MoAb) only, in this case: 4 cycles of obinutuzumab; * if less than CR (PR, SD): the immunochemotherapy program will be completed as outlined for Arm A: 2 cycles of G-CHOP Q21 + 2 cycles Q21 of obinutuzumab; Both Arms: in responding patients (CR, PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 MoAb used for induction. Patients in both arms with progressive disease at any time and patients in SD at the EOI shall be considered for salvage therapy at clinician discretion.

DRUG

Immunochemotherapy regimen: G-CVP (Arm A)

Arm A (Standard arm): 4 cycles of G-CVP Q21 (21-days cycles) G-CVP = Obinutuzumab, Cyclophosphamide, Vincristine, Prednisone. Patients will undergo an early restaging after cycle 4: those with at least a stable disease will complete the induction treatment with 4 cycles of G-CVP Q21; Both Arms: Whichever the regimen, in responding patients (Complete Remission CR, Partial Remission PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 Monoclonal Antibody (MoAb) used for induction. Patients in both arms with progressive disease at any time and patients in stable disease SD at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

DRUG

Immunochemotherapy regimen: G-CVP (Arm B)

Arm B (Experimental arm): 4 cycles of G-CVP Q21 (21-days cycles) G-CVP = Obinutuzumab, Cyclophosphamide, Vincristine, Prednisone. After cycle 4 patients will undergo an early restaging. Induction therapy shall be completed based on the response achieved and on the treatment chosen as below specified: * if in CR: patients will receive no more chemotherapy but will complete induction with the Monoclonal Antibody (MoAb) only, in this case: 4 cycles of obinutuzumab; * if less than CR (PR, SD): the immunochemotherapy program will be completed as outlined for Arm A: 4 cycles of G-CVP Q21 Both Arms: in responding patients (CR, PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 MoAb used for induction. Patients in both arms with progressive disease at any time and patients in SD at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS

  lead OTHER

Principal Investigators

• Stefano Luminari, MD · Reggio Emilia - Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-12-01

Primary Completion

2028-07-31

Completion

2030-07-31

Countries

• Italy

Study Locations