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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
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.
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
1000 mg IV on Cycle 1 Day 1.
University of Nebraska Medical Center
Omaha, Nebraska, United States
RECRUITINGAbramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
RECRUITINGAssessment of the percentage of subjects who achieve a complete metabolic response at 26 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 experienced non-hematologic dose limiting toxicity associated with early administration of Mosunetuzumab following SOC CAR-T Cell therapy.
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: 42 days from the date of first infusion of mosunetuzumab
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.
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Time frame: 63 days from the date of first infusion of glofitimab
Assessment of the percentage of subjects who experience hematologic dose limiting toxicity associated with early administration of Mosunetuzumab and glofitimab following SOC CAR-T Cell therapy in patients who stop therapy after 2 cycles.
Dose limiting hematologic toxicities will be measured by the following: ANC \< 1000/uL despite G-CSF support, Hgb \< 7 g/dL despite transfusion support, Plt \< 50,000/uL that lasts for at least 7 days Hematologic DLTS that occur within the first 60 days following CAR-T Cell therapy will not be included in this assessment.
Time frame: 63 days from the date of the first infusion or glofitimab or mosunetuzumab
Determine Response Duration
Average length of response in months of any partial or complete metabolic responses
Time frame: from time of first response assessment to up to five years from last dose of bispecific antibody therapy