Safety and Efficacy of CD19-Targeted CAR-T Therapy for Relapsed/Refractory CD19+ B Cell Leukemia and Lymphoma

Lymphoma Clinical Trial

Official title:

Safety and Efficacy of CD19-Targeted CAR-T Therapy for Relapsed/Refractory CD19+ B Cell Leukemia and Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04271800
• Other study ID #: PBC014
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 1, 2019
• Est. completion date: July 1, 2024

Study information

• Verified date: April 2023
• Source: Chongqing Precision Biotech Co., Ltd
• Contact: Zhi Yang, PhD
• Phone: 86-13206140093
• Email: yangzhi[@]precision-biotech.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single arm study to evaluate the efficacy and safety of CD19-targeted CAR-T cells therapy for patients with relapsed/refractory CD19+ B Cell Leukemia and Lymphoma.

Description:

There are limited options for treatment of relapse/refractory CD19+ B Cell Leukemia and Lymphoma. CD19 is expressed on most CD19+ B Cell Leukemia and Lymphoma cells so it is an ideal target for CAR-T. In this study, investigators will evaluate the safety and efficacy of CAR-T targeting CD19 in patients with relapsed/refractory CD19+ B Cell Leukemia and Lymphoma. The primary goal is safety and efficiency assessment, including adverse events and disease status after treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: July 1, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Signed written informed consent;

2. Diagnose as relapsed /refractory B Cell Leukemia and Lymphoma, and meet one of the following conditions:

1. Failed to standard chemotherapy regimens;

2. Relapse after complete remission, high-risk and / or refractory patients ;

3. Relapse after hematopoietic stem cell transplantation;

3. For patients with Ph + ALL, the following conditions must be met: those who have received a standard induction chemotherapy regimen and who have not achieved complete remission after TKI treatment or have relapsed after remission (cannot tolerate TKI treatment or have contraindications to TKI treatment or the presence of TKI class) Except for drug resistant patients);

4. Evidence for cell membrane CD19 expression;

5. All genders, ages: 3 to 75 years;

6. The expect time of survive is above 12 weeks;

7. KPS>60;

8. No serious mental disorders ;

9. Left ventricular ejection fraction =50%

10. Sufficient hepatic function defined by ALT/AST=3 x ULN and bilirubin=2 x ULN;

11. Sufficient renal function defined by creatinine clearance=2 x ULN;

12. Sufficient pulmonary function defined by indoor oxygen saturation=92%;

13. With single or venous blood collection standards, and no other cell collection contraindications;

14. Ability and willingness to adhere to the study visit schedule and all protocol requirements.

Exclusion Criteria:

1. Have received CAR-T therapy or other genetically modified cell therapy before screening;

2. Participated in other clinical research within 1 month before screening;

3. Have received the following anti-tumor treatment before screening: Have received chemotherapy, targeted therapy or other experimental drug treatment within 4 weeks, except those who have confirmed disease progression after treatment;

4. Live attenuated vaccine within 4 weeks before screening;

5. Convulsion or stoke within past 6 months;

6. Previous history of other malignancy;

7. Presence of uncontrolled active infection;

8. Subjects with positive HBsAg or HBcAb positive and peripheral blood HBV DNA titer is higher than the lower limit of detection of the research institution; HCV antibody positive and peripheral blood HCV RNA titer is higher than the lower limit of detection of the research institution; HIV antibody positive; syphilis primary screening antibody positive;

9. Pregnant or breasting-feeding women;

10. Any situation that investigators regard not suitable for attending in this study or may affect the data analysis.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, B-Cell
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma

Intervention

Biological:
• CD19 CAR-T cells
A single infusion of CD19-CAR-T cells will be administered intravenously.

Locations

Country	Name	City	State
China	Chongqing University Cancer Hospital	Chongqing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Chongqing Precision Biotech Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events that related to treatment	Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)	2 years
Primary	The response rate of CD19 CAR-T treatment in patients with relapse/refractory CD19+ B Cell Leukemia and Lymphoma that treatment by CD19 CAR-T cells therapy	The response rate of CD19 CAR-T treatment will be recorded and assessed according to the National Comprehensive Cancer Network Guideline	6 months
Secondary	Rate of CD19 CAR-T cells in bone marrow and peripheral blood	In vivo (bone marrow and peripheral blood) rate of CD19 CAR-T cells were determined by means of flow cytometry	2 years
Secondary	Quantity of CD19 CAR copies in bone marrow and peripheral blood	In vivo (bone marrow and peripheral blood) quantity of CD19 CAR copies were determined by means of qPCR	2 years
Secondary	Cellular kinetics of CD19 positive cells in bone marrow	In vivo (bone marrow) rate and quantity of CD19 positive cells were determined by means of flow cytometry	1 years
Secondary	Levels of Cytokines in Serum	In vivo (Serum) quantity of cytokines	3 months
Secondary	Duration of Response (DOR) of CD19 CAR-T treatment in patients with refractory/relapsed CD19+ B Cell Leukemia and Lymphoma	DOR will be assessed from the first assessment of CR/CRi to the first assessment of recurrence or progression of the disease or death from any cause (censored)	2 years
Secondary	Progress-free survival(PFS) of CD19 CAR-T treatment in patients with refractory/relapsed CD19+ B Cell Leukemia and Lymphoma	PFS will be assessed from the first CAR-T cell infusion to death from any cause or the first assessment of progression (censored)	2 years
Secondary	Overall survival(OS) of CD19 CAR-T treatment in patients with refractory/relapsed CD19+ B Cell Leukemia and Lymphoma	OS will be assessed from the first CAR-T cell infusion to death from any cause (censored)	2 years