Actively Recruiting
A Phase 2 Study Evaluating the Bispecific CD3xCD20 Antibody Glofitamab in Combination With Rituximab or Obinutuzumab Plus Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP) in Patients With Richter Syndrome as Frontline Therapy
Led by French Innovative Leukemia Organisation · Updated on 2025-12-10
40
Participants Needed
23
Research Sites
52 weeks
Total Duration
On this page
Sponsors
F
French Innovative Leukemia Organisation
Lead Sponsor
H
Hoffmann-La Roche
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating a treatment for patients with previously untreated Richter's syndrome (RS), a condition where an aggressive lymphoma develops in someone with chronic lymphocytic leukemia (CLL). This national, multicenter, non-randomized phase 2 trial aims to assess the response to a combination of therapies including R/G-CHOP plus glofitamab. The study also monitors safety, toxicity, and patient outcomes over time. Participants receive treatment in cycles lasting 21 days each. The first cycle involves standard R-CHOP chemotherapy drugs: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. In the second cycle, obinutuzumab replaces rituximab to reduce the risk of cytokine release syndrome, and glofitamab is introduced with step-up dosing. Cycles 3 to 6 combine R-CHOP with glofitamab at a fixed dose. Patients who respond well after 6 cycles receive two additional glofitamab infusions during cycles 7 and 8. Participants undergo thorough assessments before starting treatment, including medical history, physical exams, blood tests, imaging scans (CT and PET), and heart function evaluation. During treatment, safety and health are monitored regularly through exams, lab tests, and imaging after cycles 4 and 6. Follow-up visits occur every 3 months for a year after treatment ends or if treatment stops early. The main measure of success is the percentage of participants with a complete response after 6 cycles, evaluated using standardized lymphoma response criteria.
CONDITIONS
Brief Title
Evaluation of Treatment by Glofitamab in Combination With Rituximab or Obinutuzumab Plus CHOP in Patients With RIchter Syndrome
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma with biopsy-proven transformation to CD20 positive diffuse large B-cell lymphoma (Richter's syndrome) according to the 2016 WHO classification
- Fresh or archival tissue biopsy available
- Previous therapy for CLL allowed, but no prior therapy for Richter's syndrome
- Age between 18 and 80 years
- ECOG performance status of 0 to 2
- At least one measurable target lesion (≥1.5 cm) by CT scan or PET-CT with hypermetabolic lesion; patients without measurable disease but with bone marrow infiltration by Richter's syndrome are eligible
- Hematologic criteria met at screening unless significant bone marrow involvement: neutrophils ≥1.5 G/L, hemoglobin >10 g/dL, platelets ≥75 G/L
- Adequate coagulation: prothrombin time >50%, fibrinogen >1 g/L
- Adequate liver function: total bilirubin ≤1.5 x ULN; AST/ALT ≤3 x ULN
- Left ventricular ejection fraction >50%
- Adequate renal function: creatinine clearance ≥40 mL/min
- Negative serology or PCR for acute/chronic HBV, HCV, HIV
- Prior SARS-CoV-2 vaccination and negative SARS-CoV-2 PCR before each treatment cycle
- Negative pregnancy test for women of childbearing potential
- Agreement to use effective contraception or abstinence as specified
- Ability and willingness to provide informed consent and comply with study procedures including mandated hospitalization for first glofitamab dose
- Covered by a social security system
You will not qualify if you...
- Hodgkin variant of Richter's syndrome
- Prior treatment for Richter's syndrome
- Clinically relevant central nervous system disorder
- Ineligibility for full-dose CHOP
- Previous bispecific antibody treatment
- History or presence of diffuse large B-cell lymphoma in CNS
- Steroid treatment >1 mg/kg/day for one week before inclusion
- History of anaphylactic reactions to monoclonal antibodies or product components
- Prior allogeneic hematopoietic stem cell transplantation
- Active or recent infection requiring hospitalization or IV antibiotics within 4 weeks
- History of other malignancies except certain treated cancers without recurrence
- Prior solid organ transplantation
- History of severe immune-related adverse events from immunotherapy
- Uncontrolled autoimmune disease
- HIV infection
- Hepatitis B or C seropositivity unless due to vaccination
- Pregnant or breastfeeding women
- Unable or unwilling to comply with study evaluations
- Unable to provide informed consent
- Legal or psychiatric restrictions affecting participation
- Fertile males unwilling to use contraception during and 12 months after treatment
- History of macrophage activation syndrome or hemophagocytic lymphohistiocytosis
- Left ventricular ejection fraction <50% or significant cardiovascular disease
- Abnormal liver or kidney function as defined
- History of progressive multifocal leukoencephalopathy
- Severe allergic reactions to monoclonal antibody therapy
- Any condition contraindicating investigational drug use
- Recent major surgery or trauma within 28 days
- Live attenuated vaccine within 4 weeks before obinutuzumab infusion
- Participation in another investigational trial within 30 days
- Clinically significant liver disease or cirrhosis
- No social security coverage
- Inability to comply with mandated hospitalization and restrictions
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - Up to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 to 2 visits for clinical assessments, imaging, laboratory tests, and medical history review
Duration - Approximately 6 months (24 weeks)
Participants receive up to 8 cycles of combined drug treatment including R-CHOP, G-CHOP with glofitamab, and glofitamab alone.
Up to 8 treatment cycles with visits every 3 weeks; dosing includes infusions on specified days within each cycle
Duration - 12 months
Participants are monitored for safety and treatment outcomes after completing treatment.
Follow-up visits every 3 months for 1 year after last treatment or early discontinuation
Trial Site Locations
Total: 23 locations
1
Amiens-Picardie Chu
Amiens, France, 80054
Not Yet Recruiting
2
Angers Chu
Angers, France, 49933
Not Yet Recruiting
3
BAYONNE - CH de la Côte Basque - Hématologie
Bayonne, France, 64109
Not Yet Recruiting
4
Clermont-Ferrand - Chu Estaing
Clermont-Ferrand, France, 63000
Actively Recruiting
5
Grenoble - CHUGA - Hématologie Clinique
Grenoble, France, 38043
Not Yet Recruiting
6
LILLE GHICL - Hôpital Saint Vincent de Paul
Lille, France, 59000
Not Yet Recruiting
7
LILLE CHU - Hôpital Claude Huriez
Lille, France, 59037
Not Yet Recruiting
8
LIMOGES - CHU Dupuytren 1
Limoges, France, 87042
Not Yet Recruiting
9
LYON-Centre Léon Bérard
Lyon, France, 69008
Not Yet Recruiting
10
MONTPELLIER - Hôpital Saint-Eloi - Hématologie Clinique
Montpellier, France, 34295
Not Yet Recruiting
11
APHP - Hôpital Saint-Louis - Hématologie adultes
Paris, France, 75010
Not Yet Recruiting
12
APHP - Hôpital Saint-Antoine - Hématologie et thérapie cellulaire
Paris, France, 75012
Not Yet Recruiting
13
APHP - Hôpital Pitié Salpêtrière - Hématologie
Paris, France, 75651
Actively Recruiting
14
Bordeaux Pessac
Pessac, France, 33604
Not Yet Recruiting
15
LYON HCL - CH Lyon Sud
Pierre-Bénite, France, 69036
Actively Recruiting
16
Reims Chu
Reims, France, 51092
Not Yet Recruiting
17
RENNES - CHU Pontchaillou - Hématologie Clinique
Rennes, France, 35033
Not Yet Recruiting
18
ROUEN - Centre Henri Becquerel - Service Hématologie Clinique
Rouen, France, 76038
Actively Recruiting
19
Strasbourg - Icans
Strasbourg, France, 67033
Not Yet Recruiting
20
Toulouse - IUCT Oncopole - Service d'Hématologie
Toulouse, France, 31059
Actively Recruiting
21
TOURS - Hôpital Bretonneau
Tours, France, 37000
Not Yet Recruiting
22
NANCY - CHU Brabois
Vandœuvre-lès-Nancy, France, 54500
Not Yet Recruiting
23
VERSAILLES - Hôpital André Mignot
Versailles, France
Actively Recruiting
Research Team
D
David Schwartz
V
Valérie Rouillé
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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