A Safety and Efficacy Study of Defibrotide in the Prevention of Chimeric Antigen Receptor-T-cell-associated Neurotoxicity
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ClinicalTrials.gov Identifier: NCT03954106 |
Recruitment Status :
Recruiting
First Posted : May 17, 2019
Last Update Posted : March 30, 2020
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
DLBCL Neurotoxicity Syndromes | Drug: Defibrotide | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 35 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Prospective, Multicenter, Open-Label, Single Arm, Phase 2 Study to Evaluate the Safety and Efficacy of Defibrotide in the Prevention of Chimeric Antigen Receptor-T-cell-associated Neurotoxicity in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma Receiving Axicabtagene Ciloleucel (Yescarta®) |
Actual Study Start Date : | October 4, 2019 |
Estimated Primary Completion Date : | April 2021 |
Estimated Study Completion Date : | May 2021 |

Arm | Intervention/treatment |
---|---|
Experimental: 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. |
Drug: Defibrotide
Once daily on CAR-T Day -5, -4, -3 before lymphodepletion and also every 6 hours daily on CAR-T Day 0-7. |
- Incidence of CAR-T-associated neurotoxicity [ Time Frame: By CAR-T Day +30 ]Incidence of CAR-T-associated neurotoxicity (any grade, defined by CTCAE v5.0)
- Incidence of CAR-T-associated neurotoxicity of Grade 3 or greater [ Time Frame: By CAR-T Day +30 ]CAR-T-associated neurotoxicity of Grade 3 or greater defined by CTCAE v5.0
- Incidence of CAR-T-associated neurotoxicity of any grade and Grade 3 or greater [ Time Frame: By CAR-T Day +30 ]CAR-T-associated neurotoxicity (any grade and Grade 3 or greater) according to the ASBMT consensus grading system
- Incidence of CRS [ Time Frame: By CAR-T Day +30 ]Incidence of CRS (any grade, according to the ASBMT consensus grading system)
- Use of high dose steroid by CAR-T Day +30 [ Time Frame: By CAR-T Day +30 ]The use of high dose steroids is defined as a dose of dexamethasone of at least 7.5 mg/day or equivalent

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Subject must be ≥ 18 years of age at signing of informed consent.
- 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.
- 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.
- Subject must be able to understand and sign written informed consent.
Exclusion Criteria:
- Subject is currently receiving dialysis or expected to receive dialysis.
- 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.
- Subject has previously been treated with CAR-T therapy.
- Hemodynamic instability requiring vasopressors or uncontrolled hypertension with persistent systolic blood pressure > 180.
- Subject has clinically significant active bleeding, history of intracranial bleeding, or is at risk for intracranial bleeding as determined by the Investigator.
- Subject plans to use any medication that increases the risk of bleeding.
- Subject is pregnant or lactating and does not agree to stop breastfeeding.
- Subject has a known history of hypersensitivity to defibrotide or any of the excipients.
- Subject has primary CNS lymphoma.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03954106
Contact: Director Clinical Trial Disclosure & Transparency | 2159707145 | ClinicalTrialDisclosure@JazzPharma.com |
United States, Arizona | |
Mayo Clinic | Recruiting |
Phoenix, Arizona, United States, 85054 | |
United States, Maryland | |
University of Maryland | Recruiting |
Baltimore, Maryland, United States, 21201 | |
United States, Massachusetts | |
Beth Israel Deaconess Medical Center | Recruiting |
Boston, Massachusetts, United States, 02215 | |
Dana Farber Cancer Institute | Recruiting |
Boston, Massachusetts, United States, 02215 | |
United States, North Carolina | |
Duke University Medical Center | Active, not recruiting |
Durham, North Carolina, United States, 27710 |
Responsible Party: | Jazz Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT03954106 |
Other Study ID Numbers: |
JZP395-201 |
First Posted: | May 17, 2019 Key Record Dates |
Last Update Posted: | March 30, 2020 |
Last Verified: | March 2020 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
CAR-T |
Neurotoxicity Syndromes Nervous System Diseases Poisoning Chemically-Induced Disorders Defibrotide |
Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Platelet Aggregation Inhibitors |