Anti‑PD1 armored CD19 CAR‑T therapy for relapsed or refractory diffuse large B‑cell lymphoma

A Prospective, Open-label and Single-arm Study of Anti-PD1 Armored CD19 CAR-T Cells in Adult Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma

This trial will test whether anti‑PD1 armored CD19 CAR‑T cell therapy is safe and tolerable in adults with relapsed or refractory diffuse large B‑cell lymphoma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu Topcel-KH Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: CAR-T
• Locations: 1 site (Suzhou)
• Trial ID: NCT07368270 on ClinicalTrials.gov

What this trial studies

This is a prospective, open‑label, single‑arm Phase 1 dose‑escalation study enrolling adults with relapsed or refractory diffuse large B‑cell lymphoma who have CD19‑positive tumors. Participants will receive one of three escalating dose levels of anti‑PD1 armored CD19 CAR‑T cells to identify safety, tolerability, and the maximum tolerated dose, with a predefined maximum total cell dose. Secondary objectives include preliminary measures of efficacy, pharmacokinetics, and cellular persistence of the CAR‑T product. The trial requires measurable disease, ECOG ≤2, adequate organ function, and expected survival of at least three months.

Who should consider this trial

Good fit: Adults (≥18) with relapsed or refractory DLBCL who are CD19‑positive, have measurable disease, ECOG performance status ≤2, adequate organ function, and expected survival ≥3 months are the intended candidates.

Not a fit: Patients with CD19‑negative tumors, poor performance status, uncontrolled medical problems, or those who are eligible for and likely to benefit from standard curative therapies such as transplant may not receive benefit from this investigational approach.

Why it matters

Potential benefit: If successful, this therapy could offer a new treatment option that achieves deeper or more durable remissions for patients with relapsed or refractory DLBCL who have limited standard options.

How similar studies have performed: Approved CD19 CAR‑T therapies have shown high response rates in r/r DLBCL, but anti‑PD1 armored CAR‑T constructs are a relatively novel modification with limited published clinical outcome data to date.

Eligibility criteria

Inclusion Criteria:

* 1\. Subjects voluntarily participate in clinical research and sign informed consent.
* 2\. Adult subjects (age ≥18 ) with relapsed or refractory diffuse large B-cell lymphoma: a) failure to achieve CR after 6 cycles, or PR after 3 cycles, of first-line therapy, or achieve CR after first-line therapy but relapse within 12 months; b) achieve CR after systemic treatment, but are refractory or relapsed, and no plan to transplant, or prepare for transplantation but cannot meet transplantation criteria after second-line therapy; c) not achieve CR after at least two courses of second-line treatment (including autologous stem cell transplantation).
* 3\. Expected survival ≥ 3 months.
* 4\. At least one measurable lesion as per revised IWG response criteria for malignant lymphom (2014 Lugano criteria).
* 5\. CD19 positive expression are detected on tumor cells of subjects by flow cytometry or immunohistochemistry.
* 6\. ECOG score ≤ 2.
* 7\. Subjects with adequate organ functions prior to enrollment, meet the following laboratory values:
* Renal function: serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m².
* Hepatic function: Serum alanine aminotransferase (ALT) ≤ 5 × age-specific ULN and total bilirubin ≤ 2.0 mg/dL, except in subjects with Gilbert-Meulengracht syndrome. If total bilirubin ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN, subjects with Gilbert-Meulengracht syndrome are included.
* Pulmonary reserve: ≤ Grade 1 dyspnea and oxygen saturation \>95% on room air.
* 8\. Stable hemodynamics and left ventricular ejection fraction (LVEF) ≥ 45 % assessed by echocardiography or multi-gated radionuclide angiography (MUGA).
* 9\. Adequate bone-marrow reserve without blood transfusion as defined by:
* Absolute neutrophil count (ANC) ≥ 1 x 10\^9/L.
* Absolute lymphocyte count (ALC) ≥ 0.1 x 10\^9/L.
* Platelets ≥ 50 x 10\^9/L.
* Hemoglobin \>80g/L.
* 10\. In the investigator's judgment, subjects' general condition and all biochemical values are either normal or sufficiently compensated to receive lymphodepletion and CAR-T cell therapy.

Exclusion Criteria:

* 1\. Women who are pregnant or breastfeeding, or planned pregnancy within 6 months.
* 2\. Infectious disease(HIV, Active Tuberculosis ect.).
* 3\. Active infection: hepatitis B, hepatitis C.
* 4\. Abnormal vital signs or refuse to receive examination.
* 5\. Subjects with psychiatric or psychological disorders are unable to complete treatment or efficacy assessment.
* 6.History of severe hypersensitivity or known hypersensitivity to IL-2.
* 7\. Systemic or local severe infection requiring antimicrobial therapy.
* 8\. Significant dysfunction of vital organs (heart, lung, brain, kidney, etc.), or in the investigator's judgment, subjects are unable to be enrolled with any other condition.

Where this trial is running

Suzhou

• Suzhou Hongci Hematology Hospital — Suzhou, China (Recruiting)

Study contacts

• Study coordinator: Xiao Ma

Conditions Diffuse Large B Cell Lymphoma