Mosunetuzumab-Lenalidomide Versus Investigator Choices in Patients With Relapsed or Refractory Marginal Zone Lymphoma

NCT06006117 | Recruiting Phase 3

• 1 other identifier: MARSUN
• Study Type: interventional
• Target: 260
• Locations: 5 countries
• Sites: 48

Brief Summary

This is an open label, multi-center, international, randomized phase III trial to compare the efficacy of Mosunetuzumab-Lenalidomide with investigator choices exclusively in R/R MZL patients. Patients with a proven diagnosis of EMZL, SMZL or NMZL subtypes and previously treated with at least one prior systemic treatment and not more than three prior lines are eligible. Previous treatment line must include at least one systemic line with a drug targeting CD20 (monoclonal antibody at least 2 cycles) with or without chemotherapy (R-CHOP, R-Bendamustine, R-CVP, R-Chlorambucil at least 2 cycles) or targeted treatment such as Ibrutinib. The patients will be Randomized as follows: Arm A - Experimental arm:

• Mosunetuzumab-Lenalidomide Arm B - Comparator arms ( Investigator Choices):
• Rituximab-Lenalidomide
• Rituximab-Bendamustine
• Rituximab-CHOP

Conditions

Marginal Zone Lymphoma

Keywords

Bispecific antibodies, Subcutaneous; Step-up dosing; Marginal Zone Lymphoma; Investigator choices; R/R MZL

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) as determined by investigator

  according to Lugano criteria 2014

  After 122 events = approximately 4.5 years and after 163 events = approximately 6.5 years (event = progression or death)

Secondary Outcomes (35)

• Complete Response rate (CR) as determined by investigator (CR24)

  2 years

• Complete response rate (CR) by blinded central review (CR24)

  2 years

• Overall response rate (ORR) as determined by investigator

  6 months for patients with Mosunetuzumab-Lenalidomide, Rituximab-Lenalidomide or R-CHOP, 3 months for patients with Rituximab-bendamustine

• Overall response rate (ORR) as determined by investigator

  12 months

• Overall response rate (ORR) as determined by investigator

  24 months

Study Arms (4)

Arm 1: Mosunetuzumab and Lenalidomide

EXPERIMENTAL

* Mosunetuzumab will be administered SC (21 days first cycle, then 28 days next cycles) * C1 (21-days cycle): step-up dosing schedule 5 mg Day 1, 45 mg on Day 8 and 45 mg Day 15 * C2 to C12: 45 mg D1 28-days cycles * Lenalidomide PO starting dose is based on patient's creatinine clearance from Day 1 to Day 21 from cycles C2 to C6 (cycles of 28 days)

Drug: Mosunetuzumab (SC); Drug: Lenalidomide

Arm 2: Rituximab-Lenalidomide (28-days cycles)

ACTIVE COMPARATOR

* Rituximab\* 375 mg/m2 intravenously at Day 1 cycle 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2-12 * Lenalidomide PO starting dose is based on patient's creatinine clearance, D1-21 from cycle 1 to cycle 6

Drug: Rituximab (R); Drug: Lenalidomide

Arm 3: Rituximab-Bendamustine (28-days cycles)

ACTIVE COMPARATOR

* Rituximab\* 375 mg/m2 intravenously at cycle 1 Day 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2 to 6\*\* (28-days cycles) and then at D1 of three additional 56-days cycles (C7 to C9). \*\*For patients in complete response (CR) at 3 cycles, if Bendamustine is stopped, then Rituximab should also be omitted for C5 and C6. * Bendamustine IV 70 or 90 mg/m² (according to the investigator's judgment) D1 and D2/28 days x 6 cycles 28 days cycles). For patients in complete response (CR) at 3 cycles, Bendamustine and Rituximab could be stopped after 4 cycles at investigator discretion

Drug: Rituximab (R); Drug: Bendamustine

Arm 4: Rituximab-CHOP (21-days cycles)

ACTIVE COMPARATOR

* Rituximab\* 375 mg/m2 intravenously at Day 1 cycle 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2 to 6 (21-days cycles), and then at D1 of three additional 56-days cycles (C7 to C9) * CHOP, IV standard dose from cycle 1 to 6

Drug: Rituximab (R); Drug: CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone)

Interventions

Mosunetuzumab (SC) DRUG

○ Mosunetuzumab will be administered SC (21 days first cycle, then 28 days next cycles) * C1 (21-days cycle): step-up dosing schedule 5 mg Day 1, 45 mg on Day 8 and 45 mg Day 15 * C2 to C12: 45 mg D1 28-days cycles

Also known as: Mosunetuzumab

Arm 1: Mosunetuzumab and Lenalidomide

Rituximab (R) DRUG

Rituximab\* 375 mg/m2 intravenously at Day 1 cycle 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2-12

Also known as: Rituximab

Arm 2: Rituximab-Lenalidomide (28-days cycles); Arm 3: Rituximab-Bendamustine (28-days cycles); Arm 4: Rituximab-CHOP (21-days cycles)

Bendamustine DRUG

○ Bendamustine IV 70 or 90 mg/m² (according to the investigator's judgment) D1 and D2/28 days x 6 cycles 28 days cycles). For patients in complete response (CR) at 3 cycles, Bendamustine and Rituximab could be stopped after 4 cycles at investigator discretion

Arm 3: Rituximab-Bendamustine (28-days cycles)

Lenalidomide DRUG

Cycles 2 to 6 (28-day cycles): starting dose is based on patient's creatinine clearance, from day 1 to day 21, once a day, rest period from day 22 to day 28

Arm 1: Mosunetuzumab and Lenalidomide; Arm 2: Rituximab-Lenalidomide (28-days cycles)

CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone) DRUG

CHOP, IV standard dose from cycle 1 to 6

Also known as: CHOP

Arm 4: Rituximab-CHOP (21-days cycles)

Eligibility Criteria

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

You may qualify if:

• Have a diagnosis of MZL, of extranodal (EMZL) or splenic (SMZL based on the Matutes score and CD20 + CD11c + CD180 + CD43 + CD200 expression and validated by a centralized review) or nodals (NMZL) subtypes. In case of large dissemination, disseminated MZL (as evaluated by investigator; please contact the Sponsor to discuss any doubt) will be included as DMZL and included in NMZL subtype.
• Have been treated with at least one prior systemic treatment and not more than three prior lines. Previous line must include at least one systemic line with a drug targeting CD20 (monoclonal antibody at least 2 cycles; patient treated with monoclonal antibody monotherapy should have received at least 4 weekly injections) with or without chemotherapy (R-CHOP, R-Bendamustine, R-CVP, R-Chlorambucil at least 2 cycles) or targeted treatment such as Ibrutinib (at least 1 month). Patients previously treated by lenalidomide are eligible if the last administration of lenalidomide is superior to 12 months before C1D1. When randomized in comparator arm, those patients should require R-chemo. Prior local therapy (including surgery, radiotherapy antibiotics for H. pylori-positive gastric lymphoma, and antiviral for hepatitis C virus) is not considered as one line of treatment
• Signed Informed Consent Form
• Age ≥ 18 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 score (PS) of ≤ 2
• Have a symptomatic disease requiring a systemic treatment
• Not eligible for a local treatment including radiotherapy or surgery
• Stage I disease of EMZL, SMZL or NMZL may be eligible only if not candidate to local therapy (surgery or radiotherapy).
• Measurable disease in at least two perpendicular dimensions on an imaging scan is defined as: lymph node or nodal mass bi-dimensional measurement with ≥ 15 mm in longest transverse diameter or the short diameter must measure ≥ 10 mm regardless of the longest transverse diameter.
• Spleen is considered as a measurable disease if vertical axis is higher than 13 cm.
• Adequate hematopoietic function at screening as follows unless cytopenia is clearly due to marrow involvement of MZL or hypersplenism or autoimmune thrombocytopenia:
• Platelet count ≥ 75 G/L; in cases of thrombocytopenia clearly due to marrow involvement of MZL or hypersplenism or auto-immune thrombocytopenia, platelet count should be ≥ 30 G/L Washout platelet transfusion is 7 days between transfusion and D1 of starting treatment
• ANC ≥ 1 G/L unless neutropenia is clearly due to marrow involvement of MZL or hypersplenism. G-CSF is not allowed within 7 days before starting treatment
• Total hemoglobin ≥ 8 g/dL unless anemia is clearly due to marrow involvement of MZL or hypersplenism or autoimmune hemolytic anemia. Washout erythrocyte transfusion is 7 days between transfusion and D1 of starting treatment

You may not qualify if:

• MZL with histologic transformation to high-grade lymphoma
• Participants who have received any of the following treatments prior to study entry:
• Treatment with mosunetuzumab or other CD20/CD3-directed bispecific antibodies
• Allogeneic stem cell transplant
• Participants who have received any of the following treatments, whether investigational or approved, within the respective time periods prior to initiation of study treatment:
• Radiotherapy within 2 weeks prior to the first dose of study treatment
• Autologous stem cell transplant within 100 days prior to first study treatment
• Use of monoclonal antibodies within 4 weeks prior to first study treatment
• Administration of acute, low-dose, systemic immunosuppressant medications (e.g., single dose of 4 mg/day of dexamethasone for nausea or B-symptoms) is permitted during 4 days without washout.
• \- Any other anti-cancer investigational therapy within 4 weeks prior to initiation of study treatment.
• Pregnant or breastfeeding or intending to become pregnant during the study or within 28 days after the final dose of lenalidomide, 3 months after the final dose of mosunetuzumab and tocilizumab (if applicable), 12 months after the final dose of CHOP, 6 months after the final dose of bendamustine and 12 months after the final dose of rituximab (if applicable). Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment.
• Received a live, attenuated vaccine within 4 weeks before first dose of study treatment, or in whom it is anticipated that such a live attenuated vaccine will be required during the study period or within 5 months after the final dose of study treatment, except for acute pandemic situation such COVID19
• Active or history of CNS lymphoma or leptomeningeal infiltration
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins) - grade 3 and 4
• Known hypersensitivity to biopharmaceuticals produced in CHO cells or any component of the mosunetuzumab, rituximab, tocilizumab, lenalidomide, or thalidomide formulation, including Mannitol

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead

Study Sites (48)

INSTITUT JULES BORDET - Service Hématologie

Anderlecht, 1070, Belgium

NOT YET RECRUITING

UNIVERSITE CATHOLIQUE DE LOUVAIN SAINT-LUC - Service Hématologie

Brussels, 1200, Belgium

NOT YET RECRUITING

UNIVERSITAIR ZIEKENHUIS GENT - Service Hématologie

Ghent, 9000, Belgium

RECRUITING

CHU UCL NAMUR - SITE GODINNE - Service Hématologie

Yvoir, 5530, Belgium

NOT YET RECRUITING

CHU d'Amiens

Amiens, France

RECRUITING

CH d'Avignon - Hopital Henri Duffaut

Avignon, France

RECRUITING

CH de la Côte Basque - Hôpital de Bayonne

Bayonne, France

RECRUITING

CHRU Besançon - Hôpital Minjoz

Besançon, France

RECRUITING

Institut Bergonié

Bordeaux, France

RECRUITING

Chu Estaing

Clermont-Ferrand, France

RECRUITING

CHU Henri Mondor

Créteil, France

RECRUITING

CHU de Dijon

Dijon, France

RECRUITING

CHU de Grenoble - Hôpital Albert Michallon

La Tronche, France

RECRUITING

CHRU de LILLE - Claude Huriez

Lille, France

RECRUITING

Institut Paoli Calmette

Marseille, France

RECRUITING

CH Saint-Eloi

Montpellier, France

RECRUITING

CHU de Nancy - Brabois

Nancy, France

RECRUITING

Centre Catherine de Sienne

Nantes, France

RECRUITING

CHU de Nantes - Hôtel Dieu

Nantes, France

RECRUITING

Centre Antoine Lacassagne

Nice, France

RECRUITING

CHU de Nice

Nice, France

RECRUITING

CHR d'Orléans

Orléans, France

RECRUITING

APHP - Hôpital Saint Louis

Paris, France

RECRUITING

CHU Lyon Sud

Pierre-Bénite, France

RECRUITING

CHU de Rennes - Hôpital de Pontchaillou

Rennes, France

RECRUITING

Centre Henri Becquerel

Rouen, France

RECRUITING

Institut de Cancérologie de la Loire Lucien Neuwirth

Saint-Priest-en-Jarez, France

RECRUITING

KLINIKUM ST. MARIEN AMBERG - Hämatologie/Onkologie

Amberg, Germany

NOT YET RECRUITING

Helios Klinikum Berlin-Buch - Klinik für Hämatologie und Stammzelltransplantation

Berlin, Germany

NOT YET RECRUITING

UNIVERSITAETSKLINIKUM SCHLESWIG-HOLSTEIN - Med. Klinik II - Hämatologie und Onkologie

Kiel, Germany

NOT YET RECRUITING

KLINIKUM DER STADT LUDWIGSHAFEN - Hämatologie

Ludwigshafen, Germany

RECRUITING

UNIVERSITATSKLINIKUM REGENSBURG - Klinik für Innere Medizin III

Regensburg, Germany

NOT YET RECRUITING

ROBERT BOSCH KRANKENHAUS - Hämatologie, Onkologie und Palliativmedizin

Stuttgart, Germany

NOT YET RECRUITING

MUTTERHAUS DER BORROMAERINNEN - Hämatologie

Trier, Germany

NOT YET RECRUITING

UNIV KLINIKUM ULM - INNERE MEDIZIN III - Hämatologie

Ulm, Germany

NOT YET RECRUITING

UNIVERSITY WURZBURG - Hämatologie

Würzburg, Germany

NOT YET RECRUITING

POLICLINICO SANT'ORSOLA-MALPIGHI - Ematologia

Bologna, Italy

NOT YET RECRUITING

INSTITUTO ONCOLOGICO VENETO I.R.C.C.S - Ematologia

Castelfranco Veneto, Italy

NOT YET RECRUITING

AZIENDA OSPEDALIERA S. CROCE E CARLE CUNEO - Ematologia

Cuneo, Italy

NOT YET RECRUITING

SAPIENZA UNIVERSIT DI ROMA - POLO PONTINO - OSPEDALE S. MARIA GORETTI LATINA - UOC Ematologia

Latina, Italy

NOT YET RECRUITING

OSPEDALE VITO FAZZI LECCE - Hematologia

Lecce, Italy

NOT YET RECRUITING

OSPEDALE SAN RAFFAELE - Unità di Ricerca Clinica Linfomi Dipartimento di Onco-ematologia

Milan, Italy

NOT YET RECRUITING

AZIENDA OSPEDALIERO UNIVERITARIA DI MODENA - Ematologia

Modena, Italy

NOT YET RECRUITING

POLICLINICO SAN MATTEO - SC Ematologia

Pavia, Italy

NOT YET RECRUITING

OSPEDALE S. MARIA DELLE CROCI - Dipartimento di Oncologia ed Ematologia

Ravenna, Italy

NOT YET RECRUITING

AOU CITTA DELLA SALUTE E DELLA SCIENZA DI TORINO - Ematologia

Torino, Italy

NOT YET RECRUITING

OSPEDALE MAGGIORE ASUGI - UCO Ematologia

Trieste, Italy

NOT YET RECRUITING

INSTITUTO PORTUGUES DE ONCOLOGIA DE LISBOA FRANCISCO GENTIL - Departamento Hematologia

Lisbon, 1099, Portugal

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

Rituximab; Bendamustine Hydrochloride; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles

Study Officials

• Catherine THIEBLEMONT, Pr

  Lymphoma Study Association

  PRINCIPAL INVESTIGATOR

• Sylvain CARRAS

  Lymphoma Study Association

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christine STEPHAN

CONTACT

04 72 66 38 76; christine.stephan@lysarc.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Arm A - Experimental arm: Mosunetuzumab-Lenalidomide Arm B - Comparator arms (Investigator Choices): * Rituximab-Lenalidomide * Rituximab-Bendamustine * Rituximab-CHOP

Study Record Dates

• First Submitted: July 27, 2023
• First Posted: August 23, 2023
• Study Start: September 5, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2032
• Last Updated: December 19, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (11); BE (4); FR (23); PT (1); DE (9)