A Safety and Efficacy Study of Defibrotide in the Prevention of Chimeric Antigen Receptor-T-cell-associated Neurotoxicity
NCT ID: NCT03954106
Last Updated: 2021-12-09
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
25 participants
INTERVENTIONAL
2019-10-04
2020-09-30
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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NA
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Defibrotide
Part 1 (lead-in phase) will evaluate a 2.5 mg/kg/dose regimen before escalating to a 6.25 mg/kg/dose regimen.
After the Safety Assessment Committee establishes the recommended phase 2 dose based on dose-limiting toxicities during Part 1, Part 2 will enroll subjects at the recommended phase 2 dose.
Defibrotide
* 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).
Interventions
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Defibrotide
* 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).
Eligibility Criteria
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Inclusion Criteria
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
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.
18 Years
ALL
No
Sponsors
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Jazz Pharmaceuticals
INDUSTRY
Responsible Party
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Locations
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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
Duke University Medical Center
Durham, North Carolina, United States
Countries
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References
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Jacobson CA, Rosenthal AC, Arnason J, Agarwal S, Zhang P, Wu W, Amber V, Yared JA. A phase 2 trial of defibrotide for the prevention of chimeric antigen receptor T-cell-associated neurotoxicity syndrome. Blood Adv. 2023 Nov 14;7(21):6790-6799. doi: 10.1182/bloodadvances.2023009961.
Danish H, Santomasso BD. Neurotoxicity Biology and Management. Cancer J. 2021 Mar-Apr 01;27(2):126-133. doi: 10.1097/PPO.0000000000000507.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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JZP395-201
Identifier Type: -
Identifier Source: org_study_id