Phase II Study of Glofitamab With Venetoclax +/- Zanubrutinib in High-risk Mantle-cell Lymphoma

Sponsor
The Lymphoma Academic Research Organisation
Study ID
NCT06558604
Phase
PHASE2
Status
Recruiting
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Conditions

  • Lymphoma, Mantle-Cell

Eligibility Criteria

Sex
ALL
Age
18 Years - 79 Years
Healthy Volunteers
Not accepted

Interventions

  • Obinutuzumab — DRUG
    1000 mg/40mL
  • Glofitamab — DRUG
    10mg/mL
  • Venetoclax Oral Product — DRUG
    10mg, 50mg and 100mg tablets
  • Zanubrutinib Oral Capsule — DRUG
    80mg capsules

Study Details

This open-label, multicenter, three cohorts, phase II study is designed to assess a combination of Zanubrutinib/Venetoclax/Glofitamab or Venetoclax/Glofitamab in high-risk subjects with either first line or R/R Mantle Cell Lymphoma (MCL). Three independent cohorts will be run: * Cohort A will include subjects with a primary refractory or progressive disease within 24 months from initiation of first line treatment (POD 24). * Cohort B will be open for subjects with R/R MCL and refractory or progressive to a BTK inhibitor given previously (\>24 months if first line). * Cohort C will only enrol newly diagnosed and untreated MCL subjects with very high-risk features.

Key Dates

First listed
Aug 16, 2024
Start date
Feb 21, 2025
Status verified
Feb 2026
Primary completion
May 31, 2028
Completion
Mar 31, 2032

Study Design

Enrollment
100 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort A - POD24
    * Obinutuzumab IV infusion 2000 mg flat dose at C1D1 or Splited in 2 doses of 1000 mg at C1D1 and C1D2 * Glofitamab IV infusion 2.5 mg C1D8 10 mg C1D15 30 mg C2D1 and C3D1 (infusion during min 4 hours ) 30 mg Each D1 for C4 to C6 (Infusion during min 2 hours ) 30 mg Each D1 for C7 to C12 (Infusion during min 90 min) * Zanubrutinib PO 320 mg total daily dose (QD) From C1D2 continuously until end C35 * Venetoclax PO 20 mg/d C2D3 to C2D7 50 mg/d C2D8 to C2D14 100 mg/d C2D15 to C2D21 200 mg/d C3D1 to C3D7 400 mg/d From C3D8 continuously until end C35
  • Experimental: Cohort B - BTKI failure
    * Obinutuzumab IV infusion 2000 mg flat dose at C1D1 or Splited in 2 doses of 1000 mg at C1D1 and C1D2 * Glofitamab IV infusion 2.5 mg C1D8 10 mg C1D15 30 mg C2D1 and C3D1 (infusion during min 4 hours ) 30 mg Each D1 for C4 to C6 (Infusion during min 2 hours ) 30 mg Each D1 for C7 to C12 (Infusion during min 90 min) * Venetoclax PO 20 mg/d C2D3 to C2D7 50 mg/d C2D8 to C2D14 100 mg/d C2D15 to C2D21 200 mg/d C3D1 to C3D7 400 mg/d From C3D8 continuously until end C35
  • Experimental: Cohort C - first Line
    * Obinutuzumab IV infusion 2000 mg flat dose at C1D1 or Splited in 2 doses of 1000 mg at C1D1 and C1D2 * Glofitamab IV infusion 2.5 mg C1D8 10 mg C1D15 30 mg C2D1 and C3D1 (infusion during min 4 hours ) 30 mg Each D1 for C4 to C6 (Infusion during min 2 hours ) 30 mg Each D1 for C7 to C12 (Infusion during min 90 min) * Zanubrutinib PO 320 mg total daily dose (QD) From C1D2 continuously until end C35 * Venetoclax PO 20 mg/d C2D3 to C2D7 50 mg/d C2D8 to C2D14 100 mg/d C2D15 to C2D21 200 mg/d C3D1 to C3D7 400 mg/d From C3D8 continuously until end C35

Primary Outcome Measure

PFS at the end of C17 (each cycle is 21 days) [ Time Frame: end of cycle 17 (each cycle is 21 days) ]

Central Contacts