Dual CD19/CD20 cell therapy for relapsed or refractory B‑cell non‑Hodgkin lymphoma

A Phase I, Open-label Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LUCAR-E9D,LUCAR-E9K, a Dual-targeted Cell Product Targeting CD19/CD20, in Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

This trial will try a single infusion of LUCAR‑E9D or LUCAR‑E9K — engineered cells that target CD19 and CD20 — to see if they are safe and help adults with relapsed or refractory B‑cell non‑Hodgkin lymphoma.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Beijing GoBroad Hospital (other)
• Drugs / interventions: CAR-T, chemotherapy, immunotherapy, cyclophosphamide, fludarabine
• Locations: 3 sites (Hefei and 2 other locations)
• Trial ID: NCT07093411 on ClinicalTrials.gov

What this trial studies

This open‑label, early phase 1 dose‑escalation and dose‑extension trial gives eligible adults a single infusion of LUCAR‑E9D or LUCAR‑E9K after lymphodepleting chemotherapy and follows them for safety and response. The main goals are to define tolerability, identify a recommended dose, and collect preliminary evidence of anti‑tumor activity. Participants must have relapsed or refractory B‑cell non‑Hodgkin lymphoma expressing CD19 and/or CD20 and meet performance and laboratory eligibility. The protocol includes screening, pre‑treatment lymphodepletion, the cell infusion, and scheduled follow‑up visits to monitor adverse events and disease status.

Who should consider this trial

Good fit: Adults aged 18–75 with relapsed or refractory B‑cell non‑Hodgkin lymphoma that expresses CD19 and/or CD20, an ECOG performance status of 0–1, and who can undergo lymphodepleting chemotherapy and provide informed consent are eligible.

Not a fit: Patients who lack CD19/CD20 expression, have poor performance status, active uncontrolled comorbidities or CNS lymphoma, are pregnant, or are unable to tolerate lymphodepletion are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the dual‑targeted cells could produce deeper or more durable remissions by reducing tumor escape from single‑antigen therapies.

How similar studies have performed: Single‑target CD19 CAR‑T therapies have produced high response rates in relapsed/refractory B‑cell lymphomas and dual‑target approaches like CD19/CD20 are an active area with early promising but still preliminary results.

Eligibility criteria

Inclusion Criteria:

1. Subjects have fully understood the possible risks and benefits of participating in this study, are willing to follow and able to complete all trial procedures and have signed informed consent.
2. Aged 18-75 years (inclusive).
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Histologically confirmed B-cell non-Hodgkin Lymphoma that expresses at least one of CD19/CD20.
5. At least one evaluable tumor lesion according to Lugano 2014 criteria.
6. Response to prior therapy is consistent with one of the following:

1） Patients with B-NHL who are primary refractory and are unsuitable or unwilling to receive autologous CAR-T cell therapy; 2） primary refractory is defined as the best response to first-line treatment being SD or PD; 3） Relapse within 12 months after achieving CR with first-line chemotherapy and immunotherapy; 7. Life expectancy≥ 3 months 8. Women of childbearing potential must have a negative highly sensitive serum pregnancy test (β-human chorionic gonadotropin \[β-hCG\]) at screening and before the first administration of cyclophosphamide and fludarabine treatment;

Exclusion Criteria:

1. Diagnosed with or treated for other invasive malignancies besides B-cell non-Hodgkin lymphoma.
2. Active acute or chronic graft-versus-host disease (GVHD), except for grade 1 skin involvement; or requiring immunosuppressive treatment for GVHD within 4 weeks prior to enrollment;
3. Active CNS involvement (symptomatic or positive cerebrospinal fluid or imaging data), prior CNS infiltration but currently in remission (asymptomatic and negative cerebrospinal fluid and/or imaging data) is eligible;
4. Significant bleeding tendency, such as gastrointestinal bleeding, hemorrhagic cystitis, coagulopathy.
5. Chronic diseases treated with steroids or other immunosuppressants. The following situations are excluded: use of topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term use of corticosteroids for prophylaxis;
6. Severe underlying diseases, such as: - Evidence of severe active viral, bacterial infections, or uncontrolled systemic fungal infections; - Active or unstable autoimmune diseases, or autoimmune diseases within the past 3 years with potential for relapse;
7. Breastfeeding women;

Where this trial is running

Hefei and 2 other locations

• The First Affiliated Hospital of USTC (Anhui Provincial Hospital) — Hefei, China (RECRUITING)
• The Second Affiliated Hospital of Xi'an Jiaotong University — Xi'an, China (RECRUITING)
• Affiliated Hospital of Xuzhou Medical University — Xuzhou, China (RECRUITING)

Study contacts

• Study coordinator: Kai Hu

Conditions: B-cell Non-Hodgkin Lymphoma Recurrent B-cell Non-Hodgkin Lymphoma Refractory