Phase II Study of Dual Targeting of CD19 and CD20 Antigens Using Sequential CD19-directed CAR-T Cells Followed by Mosunetuzumab or Glofitamab in Relapsed or Refractory Diffuse Large B-cell or Transformed Follicular Lymphomas
Summary
The research study is being conducted to test the safety and effectiveness of the experimental drug mosunetuzumab (Cohort 1) or obinutuzumab and glofitamab (Cohort 2) when given after CAR (genetically modified) T cells. The study is for patients who have already received a CAR T-cell infusion. Some patients who join the study will receive mosunetuzumab, other patients later in the study may receive a different experimental drug (glofitamab, in combination with obinutuzumab).
Arms & interventions
- Drugmosunetuzumab
1 mg IV on Cycle 1 Day 1; 2 mg IV Cycle 1 Day 8; 60 mg IV Cycle 1 Day 15; 60 mg IV on Cycle 2 Day 1 and then 30 mg IV every 21 days beginning Cycle 2 Day 1 through Cycle 17.
- Drugglofitamab
2.5 mg IV Cycle 1 Day 8; 10 mg IV Cycle 1 Day 15 then 30 mg every 21 days beginning Cycle 2 Day 1 through Cycle 12
- Drugobinutuzumab
1000 mg IV on Cycle 1 Day 1.
Outcome measures
Primary
Assessment of the percentage of subjects who achieve a complete metabolic response at 24 weeks from date of first infusion as measured by Cheson 14 (ie Lugano) criteria
Complete response will be assessed using Cheson 2014 or Lugano criteria, utilizing simple 5 point score (Deauville score). For this study complete response will be a score of 1 (no uptake), 2 (uptake ≤ mediastinum), or 3 (uptake \>mediastinum but ≤ liver, with no new lesions, and no FDG-uptake in the bone marrow, that is not expected (i.e. due to growth factors or therapy
Time frame: 24 weeks from date of first infusion of investigational agent
Assessment of the percentage of subjects who experience non-hematologic dose limiting toxicity associated with early administration of glofitimab following SOC CAR-T Cell therapy.
Non-hematologic DLTs include the following: unexpected ≥grade 3 non-hematologic that is at least possibly related to the study drug, any grade 3 event that does not improve to ≤ grade 2 within 72 hours, any grade 3 AST, ALT or total bilirubin that lasts more than 72 hours in the absence of other causes, ≥ grade 3 neurotoxicity or seizure of any grade. Cytokine Relsease Syndrome: CRS grade 4, Grade 3 CRS that does not improve to ≤ grade 2 within 72 hours. Grade 1: Temperature ≥ 38°C, no hypotension, no hypoxia. Grade 2: Temperature ≥ 38°C, hypotension not requiring vasopressors and/or hypoxia requiring low flow nasal cannula. Grade 3: Temperature ≥ 38°C, hypotension requiring a vasopressor and/or requiring high flow oxygen. Grade 4: Temperature ≥ 38°C, hypotension requiring multiple vasopressor and/or requiring positive pressure, intubation or mechanical ventilation.
Time frame: 63 days from the date of first infusion of glofitimab
Secondary
Determine Response Duration
Time frame: from time of first response assessment to up to five years from last dose of bispecific antibody therapy
Eligibility criteria
Study locations (2)
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104