B-cell Lymphoma
Conditions
Brief summary
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.
Detailed 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.
Interventions
BIOLOGICALPD1 specific integrated anti-CD19 Chimeric Antigen Receptor T Cells
Gene editing autologous T cells with anti-CD19 ScFv expression and knockout of PD1
Sponsors
First Affiliated Hospital of Zhejiang University
Bioray Laboratories
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will receive one of the three doses of 2\*10\^6/kg, 4\*10\^6/kg,6\*10\^6/kg.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD | up to 28 days after T cell infusion | MTD will be determined based on DLTs observed during the first 28 days of study treatment. |
| RP2D | up to 28 days after T cell infusion | RP2D will be determined based on MTD and efficiency during the first 28 days of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Baseline up to 3 months after T cell infusion | Proportion of patients in whom a response among complete response and partial response as defined by standard disease-specific criteria, will be observed. |
| Progress free survival (PFS) | Baseline up to 3 months after T cell infusion | Assessed using modified Lugano classification response criteria for lymphoma (2014) |
Countries
China
Outcome results
None listed