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

B-cell Lymphoma Clinical Trial

Official title:

a Safety and Efficacy Evaluation of PD1-CD19-CART in Patients With Relapse/Refractory B-cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04213469
• Other study ID #: 2019-CAR-00CH1
• Status: Completed
• Phase: N/A
• Start date: March 13, 2020
• Est. completion date: November 10, 2023

Study information

• Verified date: January 2024
• Source: Bioray Laboratories
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 10, 2023
• Est. primary completion date: November 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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 ?-?;Primary mediastinal large B-cell lymphoma (PMBL), stage ?-?; High grade B-cell lymphoma (HGBL), stage ?-?; Mantle cell lymphoma (MCL), stage ?-?; follicular lymphoma (FL), stage ?-? 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.

Related Conditions & MeSH terms

• B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell

Intervention

Biological:
• PD1 specific integrated anti-CD19 Chimeric Antigen Receptor T Cells
Gene editing autologous T cells with anti-CD19 ScFv expression and knockout of PD1

Locations

Country	Name	City	State
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Bioray Laboratories	First Affiliated Hospital of Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD	MTD will be determined based on DLTs observed during the first 28 days of study treatment.	up to 28 days after T cell infusion
Primary	RP2D	RP2D will be determined based on MTD and efficiency during the first 28 days of study treatment.	up to 28 days after T cell infusion
Secondary	Objective response rate (ORR)	Proportion of patients in whom a response among complete response and partial response as defined by standard disease-specific criteria, will be observed.	Baseline up to 3 months after T cell infusion
Secondary	Progress free survival (PFS)	Assessed using modified Lugano classification response criteria for lymphoma (2014)	Baseline up to 3 months after T cell infusion