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

Summary

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.

Eligibility

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.

Conditions2

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