Clinical trial NCT04213469: PD1-CD19-CART in Patients With r/r B-cell Lymphoma
Official title: a Safety and Efficacy Evaluation of PD1-CD19-CART in Patients With Relapse/Refractory B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: B-cell Lymphoma
Lead sponsor: Bioray Laboratories
Sponsor class: INDUSTRY
Collaborators: name: First Affiliated Hospital of Zhejiang University
First posted: 2019-12-30
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Patients will receive one of the three doses of 2\*10\^6/kg, 4\*10\^6/kg,6\*10\^6/kg.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: MTD
timeFrame: up to 28 days after T cell infusion
measure: RP2D
timeFrame: up to 28 days after T cell infusion
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Baseline up to 3 months after T cell infusion
measure: Progress free survival (PFS)
timeFrame: Baseline up to 3 months after T cell infusion
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: the First Affliated Hospital, Zhejiang University
name: He Huang, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang J, Hu Y, Yang J, Li W, Zhang M, Wang Q, Zhang L, Wei G, Tian Y, Zhao K, Chen A, Tan B, Cui J, Li D, Li Y, Qi Y, Wang D, Wu Y, Li D, Du B, Liu M, Huang H. Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL. Nature. 2022 Sep;609(7926):369-374. doi: 10.1038/s41586-022-05140-y. Epub 2022 Aug 31.
citation: Golubovskaya V. CAR-T Cells Targeting Immune Checkpoint Pathway Players. Front Biosci (Landmark Ed). 2022 Apr 2;27(4):121. doi: 10.31083/j.fbl2704121.