Evaluation of Treatment by Glofitamab in Combination With Rituximab or Obinutuzumab Plus CHOP in Patients With RIchter Syndrome

NCT06186648 | Recruiting Phase 2 DMC

• 1 other identifier: FILOCLL015 - GLORIFY
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 23

Brief Summary

This is a national clinical trial, multicentric (28 centers), non-randomized phase 2 study. Population: Patients with previously untreated Richter's syndrome (RS), defined as the occurrence of an aggressive lymphoma (of diffuse large B-cell lymphoma histology) in a patient with chronic lymphocytic leukemia (CLL). Study treatment: The duration of each cycle is 21 days. Cycle 1: Participants will receive standard of care doses of R-CHOP in cycle 1 as follows:

• Rituximab 375 mg/m² IV Day 1
• Cyclophosphamide 750 mg/m² IV Day 1
• Doxorubicin 50 mg/m² IV Day 1
• Vincristine 1.4 mg/m² \[capped at 2.0 mg\] IV Day 1
• Prednisone 60 mg/m2 per day PO Day 1-5 Cycle 2: In order to minimize cytokine release syndrome (CRS), participants will then receive G-CHOP as cycle 2 (with obinutuzumab) and glofitamab:
• Obinutuzumab 1000 mg single dose IV Day 1
• Cyclophosphamide 750 mg/m² IV Day 1
• Doxorubicin 50 mg/m² IV Day 1
• Vincristine 1.4 mg/m² \[capped at 2.0 mg\] IV Day 1
• Prednisone 60 mg/m2 per day PO Day 1-5
• Glofitamab : administered intravenously (IV) as a step-up dose on Days 8 (2.5 mg) and 15 (10 mg) Cycle 3-6: Participants will receive standard of care doses of R-CHOP and Glofitamab as follows:
• Rituximab 375 mg/m² IV Day 1
• Cyclophosphamide 750 mg/m² IV Day 1
• Doxorubicin 50 mg/m² IV Day 1
• Vincristine 1.4 mg/m² \[capped at 2.0 mg\] IV Day 1
• Prednisone 60 mg/m2 per day PO Day 1-5
• Glofitamab : 30 mg IV Day 8 Cycle 7 and 8 (only for patient in Complete Response or Partial response after Cycle 6): Cycle 7 and 8 consist of 2 infusions of glofitamab only at D8C7 and D8C8: ● Glofitamab : 30 mg IV Day 8 Primary endpoint Percentage of participants with a complete response as assessed by the investigator using the Cheson IWG 2014 Lugano Classification (i.e. Deauville scale 1-3) after 6 cycles of R/G-CHOP + glofitamab or at permanent treatment discontinuation. End of treatment is defined as after 6 cycles of R/G-CHOP + glofitamab. Permanent treatment discontinuation is defined as the discontinuation of all treatments (R/G-CHOP, glofitamab).

Conditions

Richter Syndrome

Outcome Measures

Primary Outcomes (1)

• Objective response regarding Richter Syndrome to R/G-CHOP + glofitamab combination.

  Percentage of patients with a complete response (CR) assessed using the Cheson IWG 2014 Lugano Classification (i.e. Deauville scale 1-3)

  6 cycles (each cycle is 21 days)

Secondary Outcomes (1)

• Safety and toxicity of the R/G-CHOP + glofitamab combination

  Through treatment completion, an average of 8 months

Study Arms (1)

Glofitamab + Obinutuzumab

EXPERIMENTAL

cf Intervention

Drug: Glofitamab + Obinutuzumab

Interventions

Glofitamab + Obinutuzumab DRUG

Duration of each cycle is 21 days. Cycle 1: R-CHOP Cycle 2: G-CHOP + glofitamab (at this cycle onnly, Obinutuzumab will be injected instead of Rituximab in order to decreased the risk of cytokine released syndrome) Cycle 3-6: R-CHOP + glofitamab Cycle 7-8: glofitamab alone

Glofitamab + Obinutuzumab

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma according to the revised iwCLL criteria with biopsy proven transformation to CD20 positive diffuse large B-cell lymphoma, consistent with RS according to the 2016 WHO classification
• A fresh or archival tissue biopsy is mandatory
• Previous therapy for CLL is allowed (but no prior therapy for RS)
• Age greater than or equal to 18 years and less or equal to 80 years
• ECOG performance status 0-2
• Participants must have at least one measurable target lesion (≥ 1.5 cm) in its largest dimension by computed tomography (CT) scan. Measurable disease, defined as at least one bi-dimensionally measurable nodal or tumor lesion, defined as \> 1.5 cm in its longest dimension or PET-CT with at least one hypermetabolic lesion. Patients without measurable disease but with proven bone marrow infiltration by the RS are eligible.
• Patients must meet the following hematologic criteria at screening, unless they have significant bone marrow involvement of either CLL or RS cells confirmed on biopsy: absolute neutrophil count ≥ 1.5 G/L, hemoglobin \>10 g/dL, and platelet count ≥75 G/L independent of transfusion within 7 days of screening
• Subject must have adequate coagulation tests: Prothrombin Time \> 50%, Fibrinogen \> 1 g/L
• Adequate liver function: Total bilirubin ≤ 1.5 x ULN; Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x ULN
• Adequate left ventricular ejection function (\> 50 %)
• Adequate renal function: creatinine clearance calculated by MDRD/Cockcroft-Gault formula of ≥ 40 mL/min
• Negative serologic or PCR test results for acute or chronic HBV infection
• Negative test results for HCV and HIV (Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation)
• Prior vaccination to the SARS-Cov-2 virus and and SARS-CoV-2 PCR testing and negative result before study treatment administration at each treatment cycle
• Negative serum or urinary pregnancy test within 7 days prior to study treatment in women of childbearing potential. Patients must agree to either remain completely abstinent or to use two effective contraceptive methods\* until:

You may not qualify if:

• Patients with the Hodgkin variant of RS
• Patients with previously treated for RS
• Current or past history or presence of clinically relevant disorder affecting the central nervous system (CNS)
• Ineligible to CHOP full dose for any reason
• Previous treatment with a bispecific antibody
• Current or past history of DLBCL in the CNS (confirmed by CSF analysis)
• History of anaphylactic reactions to human, chimeric, or mouse monoclonal antibodies or to any components of the product.
• Prior allogeneic HSCT
• Patients with known acute infection or reactivation of a latent infection, whether bacterial, viral (including, but not limited to, EBV, cytomegalovirus (CMV), hepatitis B, hepatitis C, HIV and SARS-CoV-2), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 4 weeks prior to the first study treatment.
• History of other malignancies, except: i) malignancy treated with curative intent and with no recurrence over the last 3 years ii) adequately treated non-melanoma skin cancer without evidence of disease iii) adequately treated carcinoma in situ without evidence of disease
• Prior solid organ transplantation
• History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows:
• Grade ≥ 3 adverse events with the exception of Grade 3 endocrinopathy managed with replacement therapy
• Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation
• Current uncontrolled autoimmune disease\*

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead
• Hoffmann-La Roche: collaborator

Study Sites (23)

Amiens-Picardie Chu

Amiens, 80054, France

NOT YET RECRUITING

Angers Chu

Angers, 49933, France

NOT YET RECRUITING

BAYONNE - CH de la Côte Basque - Hématologie

Bayonne, 64109, France

NOT YET RECRUITING

Clermont-Ferrand - Chu Estaing

Clermont-Ferrand, 63000, France

RECRUITING

Grenoble - CHUGA - Hématologie Clinique

Grenoble, 38043, France

NOT YET RECRUITING

LILLE GHICL - Hôpital Saint Vincent de Paul

Lille, 59000, France

NOT YET RECRUITING

LILLE CHU - Hôpital Claude Huriez

Lille, 59037, France

NOT YET RECRUITING

LIMOGES - CHU Dupuytren 1

Limoges, 87042, France

NOT YET RECRUITING

LYON-Centre Léon Bérard

Lyon, 69008, France

NOT YET RECRUITING

MONTPELLIER - Hôpital Saint-Eloi - Hématologie Clinique

Montpellier, 34295, France

NOT YET RECRUITING

APHP - Hôpital Saint-Louis - Hématologie adultes

Paris, 75010, France

NOT YET RECRUITING

APHP - Hôpital Saint-Antoine - Hématologie et thérapie cellulaire

Paris, 75012, France

NOT YET RECRUITING

APHP - Hôpital Pitié Salpêtrière - Hématologie

Paris, 75651, France

RECRUITING

Bordeaux Pessac

Pessac, 33604, France

NOT YET RECRUITING

LYON HCL - CH Lyon Sud

Pierre-Bénite, 69036, France

RECRUITING

Reims Chu

Reims, 51092, France

NOT YET RECRUITING

RENNES - CHU Pontchaillou - Hématologie Clinique

Rennes, 35033, France

NOT YET RECRUITING

ROUEN - Centre Henri Becquerel - Service Hématologie Clinique

Rouen, 76038, France

RECRUITING

Strasbourg - Icans

Strasbourg, 67033, France

NOT YET RECRUITING

Toulouse - IUCT Oncopole - Service d'Hématologie

Toulouse, 31059, France

RECRUITING

TOURS - Hôpital Bretonneau

Tours, 37000, France

NOT YET RECRUITING

NANCY - CHU Brabois

Vandœuvre-lès-Nancy, 54500, France

NOT YET RECRUITING

VERSAILLES - Hôpital André Mignot

Versailles, France

RECRUITING

MeSH Terms

Interventions

glofitamab; obinutuzumab

Study Officials

• Romain guièze, MD

  Service d'hématologie clinique adulte et de thérapie cellulaire Etablissement : CHU Estaing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Schwartz

CONTACT

+33247473798; d.schwartz@filo-leucemie.org

Valérie Rouillé

CONTACT

+33247473798; v.rouille@filo-leucemie.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2023
• First Posted: January 2, 2024
• Study Start: March 21, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (23)