Safety and Efficacy Study of Anti-PD1 Armored CD19 CAR-T Cells in Adult Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma

Jiangsu Topcel-KH Pharmaceutical

Status and phase

Enrolling

Phase 1

Conditions

Diffuse Large B Cell Lymphoma

Treatments

Biological: Anti-PD1 armored CD19 CAR-T cells

Study type

Interventional

Funder types

Industry

Identifiers

NCT07368270

TH-RD09-02

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.