Eliglustat combined with CD30-targeted therapy for 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

This study tests whether adding eliglustat to CD30-targeted treatments (such as brentuximab vedotin or CD30 CAR‑T) helps people with CD30-positive lymphoma.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chinese PLA General Hospital (Academic / other)
• Drugs / interventions: immunotherapy, CAR-T, Brentuximab
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07138547 on ClinicalTrials.gov

What this trial studies

This is a single-center, open-label Phase 1/2 trial combining the glucosylceramide synthase inhibitor eliglustat with CD30-targeted immunotherapies to try to improve responses in CD30-positive lymphoma. The rationale is that inhibiting GSL synthesis may alter N-glycan structures on CD30 and enhance immune synapse formation and anti-tumor activity. Participants are adults with confirmed CD30+ lymphoma, measurable disease, and prior antitumor therapy; key endpoints include safety, complete response rate for the CAR‑T plus eliglustat arm, and progression-free survival for the brentuximab vedotin plus eliglustat arm. The trial is conducted at the People's Liberation Army General Hospital in Beijing with planned Phase I safety evaluation followed by Phase II efficacy expansion.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed CD30-positive lymphoma, ECOG <2, at least one prior line of therapy, measurable disease, and adequate organ function are the ideal candidates.

Not a fit: Patients without CD30 expression, CYP2D6 ultra-rapid metabolizers, those taking contraindicated CYP inhibitors, or patients with severe hypersensitivity to CD30-targeted agents are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, adding eliglustat could increase response rates and make CD30-targeted therapies work better and longer for patients with CD30-positive lymphoma.

How similar studies have performed: CD30-targeted agents like brentuximab vedotin and CD30 CAR‑T have shown activity but limited durable responses, and using a GSL inhibitor to modulate N-glycans is a novel approach supported mainly by preclinical and early laboratory data.

Eligibility criteria

Inclusion Criteria:

* 18 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.

Exclusion Criteria:

* 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.
* Researchers believe that other reasons are not suitable for clinical trials.

Where this trial is running

Beijing, Beijing Municipality

• People's Liberation Army General Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Han wei dong

Conditions Lymphoma