PD1-CD19-CART in Patients With r/r B-cell Lymphoma

Bioray Laboratories

Status: Completed

Conditions: B-cell Lymphoma

Treatments: Biological: PD1 specific integrated anti-CD19 Chimeric Antigen Receptor T Cells

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04213469

2019-CAR-00CH1

Details and patient eligibility

About

This is an open label, single-site, dose-escalation study in up to 25 participants with relapse/refractory B-NHL. This study aims to evaluate the safety and efficacy of the treatment with PD1-CD19-CART.

Full description

PD1-CD19-CART is a kind of chimeric antigen T cell targeting CD19 with both CD19-CAR gene integration and also PD1 knockout by one-step gene-editing. After completion of study treatment, subject participation for this study will be followed up to 15 years post T cell infusion.

Enrollment: 20 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Have the capacity to give informed consent;
2. ALL patients with the age between 18 and 70 years old;
3. Expected survival >3 moths;
4. With no severe heart and lung disease;
5. Previously confirmed diagnosis as CD19+ NHL within 6 months;
6. Hematological index as following, white blood cell (WBC)≥1.5×10^9/L，absolute neutrophil count (ANC) ≥0.8×10^9/L, Platelet count≥50×109/L, Hemoglobin (Hgb) ≥ 90mg/L, lymphocyte count≥ 0.4×10^9/L；
7. Blood biochemical index as no more than 1.5* ULN, including total bilirubin (TBIL), transglutaminase (AST), alanine aminotransferase (AST), Creatinine (SCr), Urea in patients with no tumor metastasis in liver and kidney; Blood biochemical index no more than 5* ULN in patients with tumor metastasis in liver and kidney;
8. With a stable cardiac function, the left ventricular ejection fraction (LVEF) ≥ 55%;
9. Virological tests were negative for EBV, CMV, HIV, TP and HCV; a negative HBV DNA test is acceptable if HBsAg is positive;
10. ECOG <2;
11. Relapsed or refractory (r/r) NHL including, Diffuse large B cell lymphoma(DLBCL, NOS), stage Ⅲ-Ⅳ;Primary mediastinal large B-cell lymphoma (PMBL), stage Ⅲ-Ⅳ; High grade B-cell lymphoma (HGBL), stage Ⅲ-Ⅳ; Mantle cell lymphoma (MCL), stage Ⅲ-Ⅳ; follicular lymphoma (FL), stage Ⅲ-Ⅳ and with aggression. r/r NHL defined as following, demonstrate disease that persists or relapse after achieving complete response (CR) after > 2 cycles of standard chemotherapy, or relapse after autologous hematopoietic stem cell transplantation (auto-HSCT), or not achieving CR after auto-HSCT.

Exclusion criteria

1. Pregnant or lactating women;
2. With a pregnancy plan in the next 2 years;
3. Prior treatment of anti-GVHD therapy;
4. Acceptance of allogeneic stem cell transplant (ASCT);
5. Isolated extramedullary relapse of ALL;
6. Severe mental disorders, active autoimmune diseases, active infectious diseases, severe cardiovascular diseases;
7. Partial prothrombin time or activated partial thromboplastin time or international standardized ratio > 1.5*ULN without anticoagulant treatment;
8. History of other type of maligant tumors;
9. Any circumstances that possibly increase the risk of subjects or interfere with study results, which judged by investigator.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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20 participants in 1 patient group

PD1-CD19-CART

Experimental group

Description:

Patients undergo leukapheresis. Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CART infusion. A dose of PD1-CD19-CART will be infused on day 0.

Treatment:

Biological: PD1 specific integrated anti-CD19 Chimeric Antigen Receptor T Cells