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®)

Jazz Pharmaceuticals5 sites in 1 country25 target enrollmentOctober 4, 2019

ConditionsDLBCL Neurotoxicity Syndromes

InterventionsDefibrotide

DrugsDefibrotide

Overview

Phase: Phase 2
Intervention: Defibrotide
Conditions: DLBCL
Sponsor: Jazz Pharmaceuticals
Enrollment: 25
Locations: 5
Primary Endpoint: Incidence of CAR-T-associated Neurotoxicity of Any Grade, Defined by CTCAE v5.0 by CAR-T Day +30
Status: Terminated
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

October 4, 2019

End Date

September 30, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Jazz Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

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 \>
•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.

Arms & Interventions

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.

Intervention: Defibrotide

Outcomes

Primary Outcomes

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.

Secondary Outcomes

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