This is a prospective, open-label, single-arm study evaluating the safety and efficacy of defibrotide for the prevention of CAR-T-associated neurotoxicity in subjects with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) receiving Yescarta.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
* Part 1: Defibrotide 2.5 mg/kg/dose or 6.25 mg/kg/dose once daily as a single dose on CAR-T Day -5, -4, and -3 before lymphodepletion, then every 6 hours daily for 8 days (CAR-T Day 0 to Day 7). * Part 2 Recommended Phase 2 Dose: Defibrotide 6.25 mg/kg/dose once daily as a single dose on CAR-T Day -5, -4, and -3 before lymphodepletion, then every 6 hours daily for 8 days (CAR-T Day 0 to Day 7).
Mayo Clinic
Phoenix, Arizona, United States
University of Maryland
Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Incidence of CAR-T-associated Neurotoxicity of Any Grade, Defined by CTCAE v5.0 by CAR-T Day +30
The primary efficacy endpoint was the incidence of CAR-T-associated neurotoxicity of any grade defined by CTCAE v5.0 by CAR-T Day +30. The results report the estimated percentage of participants with no CAR-T-associated neurotoxicity of any grade, defined by CTCAE v5.0, which incorporated the 2 stage design.
Time frame: By CAR-T Day +30
Incidence of CAR-T-Associated Neurotoxicity Grade 3 or Greater Defined by CTCAE v5.0 by CAR-T Day +30
The secondary efficacy endpoint was the incidence of CAR-T-associated neurotoxicity Grade 3 or greater defined by CTCAE v5.0 by CAR-T Day +30. The results report the estimated percentage of participants with no CAR-T-associated neurotoxicity (Grade 3 or greater defined by CTCAE v5.0) by CAR-T Day +30.
Time frame: By CAR-T Day +30
Incidence of CAR-T-Associated Neurotoxicity of Any Grade According to the ASBMT Consensus Grading System by CAR-T Day +30
The secondary efficacy endpoint was the incidence of CAR-T-associated neurotoxicity of any grade according to ASBMT consensus grading system by CAR-T Day +30. The results report the estimated percentage of participants with no CAR-T-associated neurotoxicity by CAR-T Day +30 summarized descriptively by any grade according to the ASBMT consensus grading system.
Time frame: By CAR-T Day +30
Incidence of CAR-T-Associated Neurotoxicity of Grade 3 or Greater According to the ASBMT Consensus Grading System by CAR-T Day +30
The secondary efficacy endpoint was the incidence of CAR-T-associated neurotoxicity grade 3 or greater according to ASBMT consensus grading system by CAR-T Day +30. The results report the estimated percentage of participants with no CAR-T-associated neurotoxicity by CAR-T Day +30 summarized descriptively by grade 3 or greater according to the ASBMT consensus grading system.
Time frame: By CAR-T Day +30
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Duke University Medical Center
Durham, North Carolina, United States
Incidence of Cytokine Release Syndrome (CRS) of Any Grade According to the ASBMT Consensus Grading System by CAR-T Day +30
The secondary efficacy endpoint was the incidence of cytokine release syndrome (CRS) of any grade according to ASBMT consensus grading system by CAR-T Day +30. The results report the estimated percentage of participants with no CRS any grade according to ASBMT criteria and was summarized descriptively using the ASBMT consensus grading system by CAR-T Day +30.
Time frame: By CAR-T Day +30
Use of High Dose Steroid By CAR-T Day +30
The percentage of participants using high dose steroids was summarized descriptively. The use of high dose steroids was defined as a dose of dexamethasone of at least 7.5 mg/day or equivalent. Only the Overall Defibrotide: 6.25 mg/kg/dose group was analyzed for this outcome.
Time frame: By CAR-T Day +30