A Safety and Efficacy Study of Defibrotide in the Prevention of Chimeric Antigen Receptor-T-cell-associated Neurotoxicity
Condition: DLBCL; Neurotoxicity Syndromes
MeSH terms: Neurotoxicity Syndromes
Intervention: Defibrotide
Intervention description: 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).
Intervention MeSH terms: Defibrotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CAR-T

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject must be ≥ 18 years of age at signing of informed consent.

          2. Subject must be diagnosed with relapsed or refractory DLBCL (including DLBCL not
             otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell
             lymphoma, and DLBCL arising from follicular lymphoma) and scheduled to receive
             treatment with Yescarta.

          3. Female subjects of childbearing potential who are sexually active and male subjects
             who are sexually active and have female partners of childbearing potential must agree
             to use a highly effective method of contraception with their partners during exposure
             to defibrotide and for 30 days after the last dose of defibrotide.

          4. Subject must be able to understand and sign written informed consent.

        Exclusion Criteria:

          1. Subject is currently receiving dialysis or expected to receive dialysis.

          2. Subject has used any investigational anticancer agent within 3 weeks prior to the
             first dose of defibrotide, or is using or plans to use any investigational agent
             during the study.

          3. Subject has previously been treated with CAR-T therapy.

          4. Hemodynamic instability requiring vasopressors or uncontrolled hypertension with
             persistent systolic blood pressure > 180.

          5. Subject has clinically significant active bleeding, history of intracranial bleeding,
             or is at risk for intracranial bleeding as determined by the Investigator.

          6. Subject plans to use any medication that increases the risk of bleeding.

          7. Subject is pregnant or lactating and does not agree to stop breastfeeding.

          8. Subject has a known history of hypersensitivity to defibrotide or any of the
             excipients.

          9. Subject has primary CNS lymphoma.