Safety and Efficacy Study of Anti-PD1 Armored CD19 CAR-T Cells in Adult Subjects With 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

The purpose of this study is to investigate the safety and tolerability of anti-PD1 armored CD19 CAR-T Cells in adult subjects with relapsed or refractory diffuse large B-cell lymphoma.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Biological: Anti-PD1 armored CD19 CAR-T cells

Detailed Description

This is a prospective, open-label, single-arm clinical study to evaluate the safety, tolerability of anti-PD1 armored CD19 CAR-T Cells in adult subjects with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL).The study plans to explore across three dose levels (1.00 × 10^6, 3.00 × 10^6, 9.00 × 10^6 CAR+ T cells/kg), and 6.00×10^8 CAR+T cells as maximum dose, aiming to evaluate the safety, tolerability of anti-PD1 armored CD19 CAR-T Cells in r/r DLBCL, explore Maximum Tolerated Dose (MTD) and determine the recommended dose for Phase II. Besides, efficacy, pharmacokinetics and persistence profile of CAR-T cells are also study objectives.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiao Ma; Phone Number: 0512-83837999; Email: colleenld2020@hotmail.com

Study Locations

• China
  • Suzhou, China
    • Recruiting
    • Suzhou Hongci Hematology Hospital
    • Contact: Xiao Ma; Phone Number: 0512-83837999; Email: colleenld2020@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anti-PD1 armored CD19 CAR-T cells treatment arm; Subjects will be administrated with Anti-PD1 armored CD19 CAR-T cells after lymphocyte depletion by fludarabine and cyclophosphamide.	Biological: Anti-PD1 armored CD19 CAR-T cells; Anti-PD1 armored CD19 CAR-T cells, single intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicity (DLT)	Dose-limiting toxicity for each subject	1 month after injection
AE/SAE	Incidence and severity of adverse events (AE), and serious adverse event (SAE)	1 month, 3 months, 6 months, 12 months after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients	1 month, 3 months, 6 months, 9 months, 12 months after injection
Overall survival (OS)	Defined as the time from the date of first infusion to death due to any cause	1 month, 3 months, 6 months, 9 months, 12 months after injection
Duration of response (DOR)	The time from the date of first response (PR or better) to the date of disease progression after infusion	1 month, 3 months, 6 months, 9 months, 12 months after injection
Progression-free survival (PFS)	The time from first infusion to the date of progression or death	1 month, 3 months, 6 months, 9 months, 12 months after injection

Collaborators and Investigators

• Sponsor: Jiangsu Topcel-KH Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: January 18, 2026
• First Submitted That Met QC Criteria: January 18, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: TH-RD09-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No