Phase III, Multicenter, Open Label, Randomized, Controlled Study Investigating Mosunetuzumab-Lenalidomide Versus Investigator Choices in Patients With Relapsed or Refractory Marginal Zone Lymphoma

Status: Recruiting
Location: See all (28) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
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

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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 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) 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 should not have received Lenalidomide before. 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:

‣ 1. 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 11.2. Absolute Neutrophil Count (ANC ) ≥ 1 G/L unless neutropenia is clearly due to marrow involvement of MZL or hypersplenism. Granulocyte Colony-Stimulating Factor (G-CSF) is not allowed within 7 days before starting treatment 11.3. 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

⁃ Serum total bilirubin ≤ 1.5 x the upper limit of normal (ULN) (or ≤3 x ULN for patients with Gilbert syndrome),

⁃ Aspartate Transaminase (AST) or ALanine Transaminase (ALT) ≤ 2.5 x ULN, unless directly attributable to the patient's MZL

⁃ Measured or estimated creatinine clearance ≥ 40 mL/min by institutional standard method

⁃ Patients who are hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (HBcAb) positive, must be negative for hepatitis B virus (HBV) polymerase chain reaction (PCR) to be eligible for study participation. Patients who are hepatitis B surface antigen (HBsAg) negative, hepatitis B surface antibody (anti-HBsAb) positive and hepatitis B core antibody (HBcAb) negative are eligible,

⁃ 16\. Contraception: 16.1. For women of childbearing potential (WOCBP) (refer to section 14.6.1 and 14.6.1.1): Serum test pregnancy at screening and Day 1 before first dose. And then monthly until end of treatment. Efficient contraceptive method is required during the treatment period (including periods of treatment interruption), for at least 28 days after the final dose of Lenalidomide (if applicable), 3 months after the final dose of Mosunetuzumab (if applicable), 6 months after the final dose of chemotherapies (if applicable) and 12 months after the final dose of Rituximab (if applicable).

‣ 2. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period (including periods of treatment interruption), and for at least 28 days after the final dose of Lenalidomide (if applicable), 3 months after the final dose of Mosunetuzumab and Tocilizumab (if applicable), 6 months after the final dose of chemotherapies (if applicable) and 12 months after the final dose of Rituximab) (if applicable).

⁃ Patient covered by any social security system (France)

Locations
Other Locations
Belgium
INSTITUT JULES BORDET - Service Hématologie
NOT_YET_RECRUITING
Anderlecht
UNIVERSITE CATHOLIQUE DE LOUVAIN SAINT-LUC - Service Hématologie
NOT_YET_RECRUITING
Brussels
UNIVERSITAIR ZIEKENHUIS GENT - Service Hématologie
NOT_YET_RECRUITING
Ghent
CHU UCL NAMUR - SITE GODINNE - Service Hématologie
NOT_YET_RECRUITING
Yvoir
France
CHU d'Amiens
RECRUITING
Amiens
CH d'Avignon - Hopital Henri Duffaut
RECRUITING
Avignon
CH de la Côte Basque - Hôpital de Bayonne
RECRUITING
Bayonne
CHRU Besançon - Hôpital Minjoz
RECRUITING
Besançon
Institut Bergonié
RECRUITING
Bordeaux
Chu Estaing
RECRUITING
Clermont-ferrand
CHU Henri Mondor
RECRUITING
Créteil
CHU de Dijon
RECRUITING
Dijon
CHU de Grenoble - Hôpital Albert Michallon
RECRUITING
La Tronche
CHRU de LILLE - Claude Huriez
RECRUITING
Lille
Institut Paoli Calmette
RECRUITING
Marseille
CH Saint-Eloi
RECRUITING
Montpellier
CHU de Nancy - Brabois
RECRUITING
Nancy
Centre Catherine de Sienne
RECRUITING
Nantes
CHU de Nantes - Hôtel Dieu
RECRUITING
Nantes
Centre Antoine Lacassagne
RECRUITING
Nice
CHU de Nice
RECRUITING
Nice
CHR d'Orléans
RECRUITING
Orléans
APHP - Hôpital Saint Louis
RECRUITING
Paris
CHU Lyon Sud
RECRUITING
Pierre-bénite
CHU de Rennes - Hôpital de Pontchaillou
RECRUITING
Rennes
Centre Henri Becquerel
RECRUITING
Rouen
Institut de Cancérologie de la Loire Lucien Neuwirth
RECRUITING
Saint-priest-en-jarez
Portugal
INSTITUTO PORTUGUES DE ONCOLOGIA DE LISBOA FRANCISCO GENTIL - Departamento Hematologia
RECRUITING
Lisbon
Contact Information
Primary
Christine STEPHAN
christine.stephan@lysarc.org
04 72 66 38 76
Time Frame
Start Date: 2023-09-05
Estimated Completion Date: 2032-09
Participants
Target number of participants: 260
Treatments
Experimental: Arm 1: Mosunetuzumab and Lenalidomide
\- Mosunetuzumab and Lenalidomide~* 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 20 mg/day from Day 1 to Day 21 from cycles C2 to C6 (cycles of 28 days)
Active_comparator: Arm 2: Rituximab-Lenalidomide (28-days cycles)
* Lenalidomide PO 20 mg/day, D1-21 from cycle 1 to cycle 6~* Rituximab\* 375 mg/m2 intravenously at Day 1 cycle 1, and then subcutaneous (1400 mg, flat dose) at D1 of cycles 2-12
Active_comparator: Arm 3: Rituximab-Bendamustine (28-days cycles)
* 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~* 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.
Active_comparator: Arm 4: Rituximab-CHOP (21-days cycles
* CHOP, IV standard dose from cycle 1 to 6~* 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)
Related Therapeutic Areas
Sponsors
Leads: The Lymphoma Academic Research Organisation

This content was sourced from clinicaltrials.gov

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