A Study of CD19/22 CART Cells Combined With PD-1 Inhibitor in Relapsed/Refractory B-cell Lymphoma

Refractory Non-Hodgkin Lymphoma Clinical Trial

Official title:

A Study Evaluated Efficacy and Safety of CD19/22 Chimeric Antigen Receptor T Cells Combined With PD-1 Inhibitor in Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04539444
• Other study ID #: CCPD-1 in lymphoma
• Status: Recruiting
• Phase: Phase 2
• Start date: August 1, 2020
• Est. completion date: February 1, 2023

Study information

• Verified date: August 2020
• Source: The First Affiliated Hospital of Soochow University
• Contact: Caixia Li, M.D.
• Phone: +86 512 67781856
• Email: licaixia[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single center, non-randomized, open-label, phase 2 study to evaluate the efficacy and safety of CD19/22 CART cells combined with PD-1 Inhibitor in relapsed/refractory B Cell Lymphoma.

Description:

Though response rates have greatly improved with the development of Chimeric antigen receptor T cells (CART) therapy in refractory/relapsed B cell non-Hodgkin's lymphoma (R/R B-NHL), the response can't usually last long and relapse occurs in a large proportion of patients who receive CART cells infusion. The main reasons of relapse might be tumor antigen loss and a lack of CART cell persistence. Currently, preclinical studies have shown that there is a synergistic effect between CAR-T cell therapy and anti-PD1 pathway, and it did have efficacy in clinic. In parallel, the combined use of CART-19 and CART-22 cells has a better potential to reduce antigen escape and increase anti-tumor activity. Therefore, the combination of CD19/22 CART and PD-1 inhibitor is one of the ways to improve the therapeutic effect of CART cells. This study was conducted to explore the efficacy and safety of CD19/22 CART cells in R/R B-NHL.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: February 1, 2023
• Est. primary completion date: February 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. R/R B-NHL with measurable (?1.5cm) lesions confirmed by pathological immunohistochemistry or flow cytometry ( meeting any of the following conditions): A.The lesion shrinkage <50% or disease progression after 4 courses of standard first-line treatment or 2 courses of two-line treatment (primary refractory disease) B. Progress disease as the best response after hematopoietic stem cell transplantation C.Progress disease or stable disease as the best response to most recent therapy regimen

2. Age = 18 years

3. The Eastern Cooperative Oncoloy Group (ECOG) physical condition score = 2 points

4. The main organ functions need to meet the following conditions:

A.Left ventricular ejection fraction =50% B.Creatinine =132umol/l or creatinine clearance =60 ml/min C.ALT and AST=2 upper limitation of normal D.SpO2 > 90%

5. Results of pregnant test should be negative, and agree to conception control during treatment and 1 year after CAR-T infusion

6. Expected survival exceeds 3 months

7. Written informed consent could be acquired

Exclusion Criteria:

1. Immunosuppressant medications or steroids was used within 2 weeks before cell collection, or need to use steroids or immunosuppressant medications more than two years

2. Uncontrolled bacteria, fungi, viruses, mycoplasma or other types of infection

3. Active hepatitis B or hepatitis C infection

4. HIV infection

5. Severe acute or chronic graft-versus-host disease (GVHD)

6. Participated in any other drug research clinical trials within 30 days before enrollment

7. Prior CART cells therapy within 3 months before enrollment

8. Prior allogeneic hematopoietic stem cell transplantation within 6 months before enrollment

9. Have contraindications to the PD-1 inhibitors

10. Uncontrolled other tumor

11. Women in pregnancy,lactation or planning to become pregnant

12. The researcher considers inappropriate to participate in this research

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Refractory Non-Hodgkin Lymphoma
• Relapsed Non Hodgkin Lymphoma

Intervention

Biological:
• CD19/22 CART
CD19/22 CART cells are administrated in a 3-day split-dose regimen at dose of 0.5- 2×10*107 CART cells per kilogram of body weight.

Drug:
• Tislelizumab
Patients will receive Tislelizumab 200mg/dose every 3 weeks.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University	Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR)	Number of patients who achieved response (complete response and partial response ) after treatment of CD19/22 CART combined with PD-1 inhibitor. Response will be assessed using the Lugano criteria.	1 year
Primary	Progression-free survival(PFS)	PFS will be assessed from the first CART cell infusion to progression,death or last follow-up.	1 year
Secondary	Complete relapse rate(CR)	Number of patients who achieved complete response after treatment by CD19/22 CART combined with PD-1 inhibitor.	1 year
Secondary	Duration of overall response (DOR)	Duration of overall response will be assessed from the first CAR-T cell infusion to progression,death or last follow-up.	1 year
Secondary	Overall survival(OS)	OS will be assessed from the first CART cell infusion to death or last follow-up.	1 year
Secondary	Incidence of treatment-related adverse events	The incidence rate of adverse events from the first day of preconditioning chemotherapy to 1 year after CART cells infusion	1 year