CHOP Plus Mosunetuzumab as First Line in Patients With Richter´s Syndrome: a Phase II Study of the Spanish Group of CLL

NCT06926205 | Recruiting Phase 2 DMC

• 2 other identifiers: GELLC-9-RICHTER/M0438802023-505621-13-00
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 16

Brief Summary

The goal of this clinical trial is to learn if drug Mosunetuzumab works to treat Richter´syndrome . It will also learn about the safety of drug Mosunetuzumab. The main questions it aims to evaluate the efficacy of mosunetuzumab combined with CHOP (M-CHOP) after the end of induction in patients with Richter´s Syndrome who have never received thearapy What medical problems do participants have when taking drug Mosunetuzumab? Patients with Richter´s Syndrome Participants will: Take drug Mosunetuzumab+CHOP during 6 cycle and they if they are not candidate to Alothasplant continuing 11 cycles more with mosunetuzumab on monoterapy Visit the clinic once every 23weeks for checkups and tests

Conditions

Richter Syndrome

Keywords

Richter Syndrome

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy of mosunetuzumab combined with CHOP (M-CHOP) after the end of induction (EoI) in patients with RS who have never received therapy.

  Primary endpoint will be complete remission (CR) evaluated by an independent review committee according to modified Lugano classification using PET/CT scan (Cheson et al. 2016) after the EoI visit. CR is defined as a score of 1, 2 or 3 for lymph nodes and extra-lymphatic sites at PET without new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. All PET evaluable in patients with at least one dose of mosunetuzumab will be included in the efficacy population.

  During 6 cycles (up to 6 months)

Secondary Outcomes (6)

• To evaluate the efficacy of mosunetuzumab combined with CHOP (M-CHOP) after the end of induction (EoI) and maintenance (EoM) in patients with therapy naive RS

  During induction ( 6 Cycles- up to 6 months) and manteinace ( 11 cycles more-up to 11 months)

• To evaluate the efficacy of mosunetuzumab combined with CHOP (M-CHOP) after the end of induction (EoI) and maintenance (EoM) in patients with therapy naive RS

  During induction ( 6 Cycles- up to 6 months) and manteinace ( 11 cycles more-up to 11 months)

• To evaluate the efficacy of mosunetuzumab combined with CHOP (M-CHOP) after the end of induction (EoI) and maintenance (EoM) in patients with therapy naive RS

  During induction ( 6 Cycles- up to 6 months) and manteinace ( 11 cycles more-up to 11 months)

• To evaluate the efficacy of mosunetuzumab combined with CHOP (M-CHOP) after the end of induction (EoI) and maintenance (EoM) in patients with therapy naive RS

  During induction ( 6 Cycles- up to 6 months) and manteinace ( 11 cycles more-up to 11 months)

• To determine the incidence and severity of adverse events.

  During induction ( 6 Cycles- up to 6 months) and manteinace ( 11 cycles more-up to11 months)

Other Outcomes (4)

• Biomarkers Objetive: To evaluate the relationship between various screening prognostic markers (clinical and biological) and clinical outcomes

  during induction (6 Cycles- up to 6 months) and maintenace ( 11 cycles more- up to 11 months)

• Biomarkers Objetive: To evaluate the relationship between various screening prognostic markers (clinical and biological) and clinical outcomes

  during induction (6 Cycles- up to 6 months) and maintenace ( 11 cycles more- up to 11 months)

• Biomarkers Objetives: To assess MRD using several technologies, including ctDNA

  During induction ( 6 Cycles- up to 6 months) and manteinace ( 11 cycles more- up to11 months)

Study Arms (1)

Mosunetuzumab

EXPERIMENTAL

6 cycle of mosunetuzumab+CHOP and then 11 cycles more of Mosunetuzumab on monotherapy.

Drug: Mosunetuzumab (IV)

Interventions

Mosunetuzumab (IV) DRUG

6 cycle of Mosunetuzumab+CHOP and then 11 cycles more of mosunetuzumab on mnotherapy

Mosunetuzumab

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent as described in Section 13.2, which includes compliance with the requirements and restrictions listed in the Informed Consent Form and this protocol.
• Aged between 18 and 79 years at the time of signing the Informed Consent Form
• Ability to comply with the study protocol and procedures and required hospitalizations, in the investigator's judgement.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.
• Adult patients with previously untreated, histologically proven Richter's syndrome, diffuse large B cell variants, following WHO 2008 criteria (Swerdlow SH, 2008).
• Screening flow cytometry or immunohistochemistry (IHC) evidence of CD20 positive disease as per central review (dim expression of CD20 is acceptable)
• Adequate BM function independent of growth factor or transfusion at screening as follows unless cytopenia is clearly due to marrow involvement of CLL:
• Platelet count ≥75 x 109/L; in cases of thrombocytopenia clearly due to marrow involvement of CLL (per the discretion of the investigator), platelet count should be ≥ 30 x 109/L.
• ANC ≥1 x 109/L unless neutropenia is clearly due to marrow involvement of CLL (per the discretion of the investigator)
• Total hemoglobin ≥ 9 g/dL unless anemia is due to marrow involvement of CLL (per the discretion of the investigator)
• Measured or estimated creatinine clearance ≥ 45 mL/min by institutional standard method.
• Life expectancy \> 3 months
• For women of childbearing potential (WOCBP): agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year, and agreement to refrain from donating eggs, during the treatment period and for at least 3 months after the last dose of mosunetuzumab and 3 months after the last dose of tocilizumab (if applicable).
• It is recommended to remain abstinent or use contraception for 12 months after the final dose of cyclophosphamide, doxorubicin, or vincristine.
• A woman is considered to be of childbearing potential (WOCBP) if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.

You may not qualify if:

• Pregnant or breastfeeding or intending to become pregnant during the study or within 3 months after the final dose of mosunetuzumab.
• a) WOCBP must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment. If a serum pregnancy test has not been performed within 14 days prior to receiving first study treatment, a negative urine pregnancy test result (performed within 7 days prior to study treatment) must be available.
• Participants who have received any of the following treatments prior to study entry:
• a) Treatment with mosunetuzumab or other CD20/CD3-directed bispecific antibodies.
• Participants who have received any of the following treatments, whether investigational or approved, given to treat RS, within the respective time periods prior to initiation of study treatment:
• Autologous SCT within 100 days prior to first mosunetuzumab administration.
• Allogeneic stem cell transplant for CLL
• CAR T-cell therapy for CLL within 100 days before first study treatment
• Systemic corticosteroid treatment ≤ 20 mg/day prednisone or equivalent to control symptoms related to disease progression for a maximum of 5 days before starting C1D1 and inhaled corticosteroids are permitted.
• Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging.
• Transformation of CLL to prolymphocytic leukemia.
• History of prior malignancy, except for conditions as listed below if patients have recovered from the acute side effects incurred as a result of previous therapy:
• Malignancies treated with curative intent and with no known active disease present for ≥ 2 years before enrollment.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated cervical carcinoma in situ without evidence of disease.

Sponsors & Collaborators

• GELLC (Grupo Español de Leucemia Linfocítica Crónica): lead
• Evidenze Health España (CRO): collaborator

Study Sites (16)

Hospital Vall Hebron

Barcelona, Barcelona, 08035, Spain

RECRUITING

Hospital Clínic y Porvincial de Barcelona

Barcelona, Barcelona, 08036, Spain

RECRUITING

ICO Hospitalet Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

H Marqués de Valdecilla

Santander, Cantabria, 39011, Spain

RECRUITING

Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, 35010, Spain

ACTIVE NOT RECRUITING

Hospital Universitario La Princesa

Madrid, Madrid, 28006, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

RECRUITING

Hospital General Universitario Morales Meseguer

Murcia, Murcia, 30008, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Costa del Sol

Marbella, Málaga, 29603, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

RECRUITING

Hospital Universitario de Salamanca

Salamanca, Salamanca, 37007, Spain

ACTIVE NOT RECRUITING

Hospital de Donostia

Donostia / San Sebastian, San Sebastian, 20014, Spain

RECRUITING

Centro Hospitalario Universitario de Santiago

Santiago de Compostela, Santiago de Compostela, 15706, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, Sevilla, 41013, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Clínico de Valencia

Valencia, Valencia, 46010, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Lozano Blesa

Zaragoza, Zaragoza, 50009, Spain

ACTIVE NOT RECRUITING

Central Study Contacts

Ana Méndez, Sponsor representative

CONTACT

+34 942 203450; administracion@gellc.es

Teresa Pascual Tome, CRO representative

CONTACT

+34 91 456 11 05; t.pascual@evidenze.com

Study Design

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

Model Details: 6 cycle of Mosunetuzumab+CHOP and den 11 cycle more of mosunetuzumab on monotherapy to first line of patients with Richter Syndrome

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: April 13, 2025
• Study Start: May 15, 2024
• Primary Completion (Estimated): May 15, 2028
• Study Completion (Estimated): May 15, 2028
• Last Updated: April 13, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (16)