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

Sponsor
The Lymphoma Academic Research Organisation
Study ID
NCT06006117
Phase
PHASE3
Status
Recruiting
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Conditions

  • Marginal Zone Lymphoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

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
  • 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
  • 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
  • CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone) — DRUG
    CHOP, IV standard dose from cycle 1 to 6
  • 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

Study Details

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

Key Dates

Start date
Sep 5, 2023
Status verified
Jan 2025
Primary completion
Sep 30, 2027
Completion
Sep 30, 2032

Study Design

Enrollment
260 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm 1: 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 starting dose is based on patient's creatinine clearance from Day 1 to Day 21 from cycles C2 to C6 (cycles of 28 days)
  • Active Comparator: Arm 2: Rituximab-Lenalidomide (28-days cycles)
    * 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
  • Active Comparator: Arm 3: Rituximab-Bendamustine (28-days cycles)
    * 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
  • Active Comparator: Arm 4: Rituximab-CHOP (21-days cycles)
    * 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

Primary Outcome Measure

Progression-free survival (PFS) as determined by investigator [ Time Frame: After 122 events = approximately 4.5 years and after 163 events = approximately 6.5 years (event = progression or death) ]

Central Contacts

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