NCT07138547

GSL Synthetase Inhibitor Eliglustat Combined With CD30 Target Immunotherapy for the Treatment of of CD30+ Lymphoma

GSL Synthetase Inhibitor Eliglustat Combined With CD30 Target Immunotherapy for the Treatment of of CD30+ Lymphoma: an Open-Label, Randomized, Phase I/II Study

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Chinese PLA General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Targeted therapy against the CD30 molecule has achieved some progress in CD30-positive Hodgkin lymphoma, but its efficacy remains unsatisfactory. Previous studies have demonstrated that N-glycan modifications in the extracellular domain of target proteins can disrupt immune synapse formation with CAR-T cells. Our preliminary research has shown that ablation of N-glycans on CD30 enhances the anti-tumor effect of CD30-targeted therapy.It is hypothesized that Eliglustat, by inhibiting GSL synthesis,may potentiate the anti-tumor effect. Consequently,we designed and initiated a single-center, open-label phase I/II clinical study to evaluate the efficacy and feasibility of Eliglustat combined with CD30 targeted immunotherapy in patients with CD30-positive lymphoma. The primary endpoint of this study is the safety and efficacy of Eliglustat combined with CD30 targeted therapies.

Detailed description

CD30-targeted therapies, including Brentuximab Vedotin (BV) and CD30-targeted CAR-T cells, have demonstrated limited efficacy in Hodgkin lymphoma,facing challenges such as the lack of durable responses with BV and low complete response (CR) rates with CD30 CAR-T cells. Existing research indicates that N-glycan modifications in the extracellular domain of target proteins may mediate resistance of tumor cells to CAR-T cell therapy.Our preliminary studies have demonstrated that disrupting the CD30 N-glycans in HL tumor cells enhances the anti-tumor effect of CD30-targeted therapy. Based on this, we hypothesize that the glucosylceramide synthase (GSL synthesis) inhibitor Eliglustat, by inhibiting GSL synthesis, may affect N-glycan structure of target proteins and consequently enhancing anti-tumor efficacy. To further validate the role of Eliglustat in modulating anti-tumor therapy for CD30-positive lymphoma, we designed and initiated a single-center, open label phase I/II clinical study. This study aims to evaluate the efficacy and feasibility of Eliglustat combined with CD30 immunotherapy in patients with CD30-positive lymphoma.Primary Endpoints:1）safety and of Eliglustat combined with CD30 targeted therapies；2）CR rate (%) in the CAR-T cell plus Eliglustat treatment group; Progression-free survival (PFS) in the BV plus Eliglustat treatment group.Secondary Endpoints: 1)Other efficacy indicators (e.g., Objective Response Rate \[ORR\]) of Eliglustat combined with CD30- targeted molecular therapy; 2) Efficacy biomarkers.

Conditions

• Lymphoma

Interventions

Type	Name	Description
DRUG	Eliglustat, CD30 target immunotherapy	Eliglustat 63mg will be administered twice daily in the first 14 days and the following every other week. CD30 target immunotherapy：Brentuximab Vedotin or CD30-targeting CAR-T Cell Therapy.

Timeline

• Start date: 2025-12-26
• Primary completion: 2028-08-31
• Completion: 2029-08-31
• First posted: 2025-08-24
• Last updated: 2026-01-02

Locations

1 site across 1 country: China