A Safety and Efficacy Study of Defibrotide in the Prevention of Chimeric Antigen Receptor-T-cell-associated Neurotoxicity
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03954106 |
Recruitment Status :
Terminated
(Primary endpoint would unlikely to be met based on the unplanned interim assessment on the first 20 efficacy evaluable patients.)
First Posted : May 17, 2019
Results First Posted : December 9, 2021
Last Update Posted : December 9, 2021
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
DLBCL Neurotoxicity Syndromes | Drug: Defibrotide | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 25 participants |
Allocation: | N/A |
Intervention Model: | Sequential 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 |
Actual Primary Completion Date : | September 18, 2020 |
Actual Study Completion Date : | September 30, 2020 |

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
|
- Incidence of CAR-T-associated Neurotoxicity of Any Grade, Defined by CTCAE v5.0 by CAR-T Day +30 [ Time Frame: 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.
- Incidence of 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 ]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.
- Incidence of CAR-T-Associated Neurotoxicity of Any Grade According to the ASBMT Consensus Grading System by CAR-T Day +30 [ Time Frame: 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.
- Incidence of CAR-T-Associated Neurotoxicity of Grade 3 or Greater According to the ASBMT Consensus Grading System by CAR-T Day +30 [ Time Frame: 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.
- Incidence of Cytokine Release Syndrome (CRS) of Any Grade According to the ASBMT Consensus Grading System by CAR-T Day +30 [ Time Frame: 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.
- Use of High Dose Steroid By CAR-T Day +30 [ Time Frame: 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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
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
United States, Arizona | |
Mayo Clinic | |
Phoenix, Arizona, United States, 85054 | |
United States, Maryland | |
University of Maryland | |
Baltimore, Maryland, United States, 21201 | |
United States, Massachusetts | |
Beth Israel Deaconess Medical Center | |
Boston, Massachusetts, United States, 02215 | |
Dana Farber Cancer Institute | |
Boston, Massachusetts, United States, 02215 | |
United States, North Carolina | |
Duke University Medical Center | |
Durham, North Carolina, United States, 27710 |
Documents provided by Jazz Pharmaceuticals:
Responsible Party: | Jazz Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT03954106 |
Other Study ID Numbers: |
JZP395-201 |
First Posted: | May 17, 2019 Key Record Dates |
Results First Posted: | December 9, 2021 |
Last Update Posted: | December 9, 2021 |
Last Verified: | November 2021 |
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 |