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

NCT07138547 | Recruiting Phase 1

• 1 other identifier: CHN-PLAGH-BT-097
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Lymphoma

Outcome Measures

Primary Outcomes (3)

• Number of Subjects with treatment-related adverse events (AEs)

  Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0.

  Up to 120 days after the last dose of study drugs]

• CR rate (CRR) in the CAR-T cell plus Eliglustat treatment group

  The Complete Response Rate (CRR), as assessed by the investigator, is the proportion of all evaluable subjects who achieve a complete response.

  12 months

• Progression-free survival (PFS) in the BV plus Eliglustat treatment group.

  Time from the date of first administration of the study drug to disease progression or death from any cause (any earliest date).

  2 years

Secondary Outcomes (2)

• Objective Response Rate [ORR]

  12 months

• CR rate (CRR) /Progression-free survival (PFS)based on CD30 expression level in tumor tissue.

  12 months

Study Arms (1)

Patients with CD30+ lymphoma

EXPERIMENTAL

Eliglustat 63mg will be administered twice daily in patients who are CYP2D6 extensive metabolizers (EMs), or intermediate metabolizers (IMs), in the first 14 days and the following every other week until 24 weeks. For patients who still benefit from the trial, eliglustat 63mg will be administered twice daily every other week to 96 weeks. CD30 target immunotherapy: Brentuximab Vedotin 1.2-1.8mg/kg day 1 Q21d; or CD30-targeting CAR-T Cell Therapy( Application should be in accordance with the specific instructions for each cell preparation).

Drug: Eliglustat, CD30 target immunotherapy

Interventions

Eliglustat, CD30 target immunotherapy DRUG

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.

Patients with CD30+ lymphoma

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 75 years of age.
• ECOG performance of less than 2.
• Subjects must have histological confirmation CD30+ lymphoma.
• Patients must have at least one line of antitumor therapy
• Life expectancy of at least 3 months.
• Subjects with lymphoma must have at least one measureable lesion \>1cm as defined by lymphoma response criteria.
• Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to ≤ grade 1 toxicity.
• Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months.
• Subjects must have adequate marrow, live, renal and heart functions.

You may not qualify if:

• Participants with CD30- lymphoma.
• CYP2D6 ultra-rapid metabolizers (URMs).
• The patients is taking a CYP2D6 inhibitor and/or concomitantly with a strong or moderate CYP3A inhibitor.
• Subjects with a history of severe hypersensitivity reactions to CD30 target immunotherapy.
• History of allergy or intolerance to study drug components.
• Known brain metastases or active central nervous system (CNS). Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening.
• Uncontrolled intercurrent illness, including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.
• Known positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS).
• Previous or concurrent cancer within 3 years prior to treatment start except for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\].
• Major surgery or trauma occurred within 28 days prior to enrollment, or major side effects have not been recovered.
• Vaccination within 30 days of study enrollment.
• Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1 month.
• Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented
• Being participating any other trials or withdraw within 4 weeks.
• Unable to swallow and retain oral medication, malabsorption syndrome, conditions that significantly impair gastrointestinal function, total gastrectomy or small bowel resection, ulcerative colitis, symptomatic inflammatory bowel disease, partial or complete intestinal obstruction.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

People's Liberation Army General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

MeSH Terms

Conditions

Lymphoma

Interventions

eliglustat

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Han wei dong

CONTACT

+861055499341; hanwdrsw@sina.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Biotherapeutic Department

Study Record Dates

• First Submitted: August 14, 2025
• First Posted: August 24, 2025
• Study Start: December 26, 2025
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2029
• Last Updated: January 2, 2026

Record last verified: 2025-12

Locations

CN (1)