Safety and Efficacy of CD123-Targeted CAR-T Therapy for Relapsed/Refractory Acute Myeloid Leukemia

Leukemia Clinical Trial

Official title:

Safety and Efficacy of CD123-Targeted CAR-T Therapy for Relapsed/Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04272125
• Other study ID #: PBC016
• 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 CD123-targeted CAR-T cells therapy for patients with relapsed/refractory Acute Myeloid Leukemia.

Description:

There are limited options for treatment of relapse/refractory Acute Myeloid Leukemia. CD123 is expressed on most myeloid leukemia cells so it is an ideal target for CAR-T. Some researches have revealed that CD123 is a marker of leukemia stem cells, which indicates that the eradication of CD123 cells may prevent relapse of leukemia. In this study, investigators will evaluate the safety and efficacy of CAR-T targeting CD123 in patients with relapsed/refractory Acute Myeloid Leukemia. 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 acute myeloid leukemia, 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. Evidence for cell membrane CD123 expression;

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

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

6. KPS>60;

7. No serious mental disorders ;

8. Left ventricular ejection fraction =50%

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

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

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

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

13. 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, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• CD123 CAR-T cells
A single infusion of CD123-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 CD123 CAR-T treatment in patients with relapse/refractory Acute Myeloid Leukemia that treatment by CD123 CAR-T cells therapy	The response rate of CD123 CAR-T treatment will be recorded and assessed according to the National Comprehensive Cancer Network Guideline	6 months
Secondary	Rate of CD123 CAR-T cells in bone marrow and peripheral blood	In vivo (bone marrow and peripheral blood) rate of CD123 CAR-T cells were determined by means of flow cytometry	2 years
Secondary	Quantity of CD123 CAR copies in bone marrow and peripheral blood	In vivo (bone marrow and peripheral blood) quantity of CD123 CAR copies were determined by means of qPCR	2 years
Secondary	Cellular kinetics of CD123 positive cells in bone marrow	In vivo (bone marrow) rate and quantity of CD123 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 CD123 CAR-T treatment in patients with refractory/relapsed acute myeloid leukemia	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 CD123 CAR-T treatment in patients with refractory/relapsed acute myeloid leukemia	PFS will be assessed from the first CAR-T cell infusion to death from any cause or the first assessment of progression (censored)	2 year
Secondary	Overall survival(OS) of CD123 CAR-T treatment in patients with refractory/relapsed acute myeloid leukemia	OS will be assessed from the first CAR-T cell infusion to death from any cause (censored)	2 years