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

Phase 1

Recruiting

• Conditions: Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, B-Cell; Leukemia
• Interventions: Biological: CD19 CAR-T cells

• Registration Number: NCT04271800
• Lead Sponsor: Chongqing Precision Biotech Co., Ltd

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2019-12-01
• Study First Submitted: 2020-02-13
• Study First Submitted QC: 2020-02-14
• Study First Posted: 2020-02-17
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-16
• Last Update Posted: 2023-04-18
• Primary Completion: 2023-12-31
• Study Completion: 2024-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD19 CAR-T cells treat	CD19 CAR-T cells	Patients will be be treated with CD19 CAR-T cells

Primary Outcome Measures

Name	Time	Method
Adverse events that related to treatment	2 years	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)
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	6 months	The response rate of CD19 CAR-T treatment will be recorded and assessed according to the National Comprehensive Cancer Network Guideline

Secondary Outcome Measures

Name	Time	Method
Progress-free survival(PFS) of CD19 CAR-T treatment in patients with refractory/relapsed CD19+ B Cell Leukemia and Lymphoma	2 years	PFS will be assessed from the first CAR-T cell infusion to death from any cause or the first assessment of progression (censored)
Quantity of CD19 CAR copies in bone marrow and peripheral blood	2 years	In vivo (bone marrow and peripheral blood) quantity of CD19 CAR copies were determined by means of qPCR
Levels of Cytokines in Serum	3 months	In vivo (Serum) quantity of cytokines
Overall survival(OS) of CD19 CAR-T treatment in patients with refractory/relapsed CD19+ B Cell Leukemia and Lymphoma	2 years	OS will be assessed from the first CAR-T cell infusion to death from any cause (censored)
Duration of Response (DOR) of CD19 CAR-T treatment in patients with refractory/relapsed CD19+ B Cell Leukemia and Lymphoma	2 years	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)
Rate of CD19 CAR-T cells in bone marrow and peripheral blood	2 years	In vivo (bone marrow and peripheral blood) rate of CD19 CAR-T cells were determined by means of flow cytometry
Cellular kinetics of CD19 positive cells in bone marrow	1 years	In vivo (bone marrow) rate and quantity of CD19 positive cells were determined by means of flow cytometry

Trial Locations

Locations (1)

Chongqing University Cancer Hospital; 🇨🇳 Chongqing, Chongqing, China