M-CHOP in Richter´s Syndrome
NCT Number: NCT06521996
Acronym: GELLC-9Richter
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Richter Syndrome|Chronic Lymphocytic Leukemia
Interventions: BIOLOGICAL: Mosunetuzumab|DRUG: CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
Sponsor: GELLC (Grupo Español de Leucemia Linfocítica Crónica)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 34
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-04-26
Completion Date: 2029-10-01
Locations: H. Clínic i Provincial, Barcelona, Spain|H. Vall d'Hebrón, Barcelona, Spain|ICO Duran i Reynals, Barcelona, Spain|C. H. U. de Gran Canaria Dr. Negrín, Las Palmas De Gran Canaria, Spain|H. U. 12 de Octubre, Madrid, Spain|H. U. La Princesa, Madrid, Spain|H. Costa del Sol, Marbella, Spain|H. G. U. Morales Meseguer, Murcia, Spain|H. U. Central de Asturias, Oviedo, Spain|H. U. de Salamanca, Salamanca, 37007, Spain|H. U. de Donostia, San Sebastián, Spain|H. U. Marqués de Valdecilla, Santander, Spain|C. H. U. de Santiago, Santiago De Compostela, Spain|H. U. Virgen del Rocío, Sevilla, Spain|H. C. U. de Valencia, Valencia, Spain|H. Lozano Blesa, Zaragoza, Spain

Summary:
The purpose of the study is to assess the efficacy, safety and tolerability of mosunetuzumab combined with CHOP in patients with untreated DLBCL-RS syndrome, identifying biological factors to address the probability of response.

In addition, efficacy and tolerability of maintenance with mosunetuzumab in patients not receiving an allo-SCT will be ascertained.

Primary Outcome Measures: Complete remission (CR), The number and percentage of patients with CR will be analyzed at 8-12 weeks after the end of induction (as primary endpoint by Lugano criteria) and at the end of maintenance (as secondary endpoint by Lugano and iwCLL criteria).

CR is defined as a score of 1, 2 or 3 (no uptake above background) for lymph nodes and extra-lymphatic sites at PET/CT without new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. In addition, to evaluate CR as per iwCLL criteria at the end of maintenance, patients need to have a normal blood count with normal/immunohistochemistry (IHC)-negative bone marrow morphology., 8-12 weeks after the end of induction|Overall Response Rate (ORR), The number and percentage of patients with a CR or PR will be analyzed 3 weeks after the end of induction (EoI) and 8-12 weeks the end of maintenance (EoM). The analysis will be performed in the ITT population, 8-12 weeks after the end of induction|Minimal-residual disease (MRD), The number and percentage of patients with MRD-negativity (defined as \< 1 CLL cell in 10,000 leukocytes), assessed by flow cytometry in responders (CR/PR) in PB and/or BM at 3 weeks after the EoI and 8-12 weeks after the EoM.

Response endpoints will be summarized using descriptive statistics along with 2-sided 95% CIs for proportions (CR, ORR, MRD) using the Clopper-Pearson exact method, 8-12 weeks after the end of induction
Secondary Outcome Measures: Progression-free survival (PFS), The time from the first dose of study treatment to the first occurrence of disease progression (assessed by the local investigator per Lugano criteria (PET) or death from any cause, whichever occurs first)., Up to 10 months|Overall Survival (OS), OS is defined as the time from first dose to death from any cause. Participants who do not die during the study will be censored at the last follow-up. This analysis will be performed in the ITT population, Up to 21 months|Duration of Response (DoR), DOR, defined as the time from best overall response (the first occurrence of a documented objective response) to disease progression (by Lugano) or death from any cause, whichever occurs first. Participants who do not experience disease progression, relapse, or die during the study will be censored at the date of their last tumor assessment. Only patients with a CR or PR will be included in the analysis., Up to 4 years