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

Phase 1

Recruiting

• Conditions: Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia
• Interventions: Biological: CD123 CAR-T cells

• Registration Number: NCT04272125
• Lead Sponsor: Chongqing Precision Biotech Co., Ltd

Brief 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.

Detailed 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.

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 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD123 CAR-T cells treat	CD123 CAR-T cells	Patients will be be treated with CD123 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 CD123 CAR-T treatment in patients with relapse/refractory Acute Myeloid Leukemia that treatment by CD123 CAR-T cells therapy	6 months	The response rate of CD123 CAR-T treatment will be recorded and assessed according to the National Comprehensive Cancer Network Guideline

Secondary Outcome Measures

Name	Time	Method
Rate of CD123 CAR-T cells in bone marrow and peripheral blood	2 years	In vivo (bone marrow and peripheral blood) rate of CD123 CAR-T cells were determined by means of flow cytometry
Cellular kinetics of CD123 positive cells in bone marrow	1 years	In vivo (bone marrow) rate and quantity of CD123 positive cells were determined by means of flow cytometry
Levels of cytokines in serum	3 months	In vivo (serum) quantity of cytokines
Duration of Response (DOR) of CD123 CAR-T treatment in patients with refractory/relapsed acute myeloid leukemia	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)
Quantity of CD123 CAR copies in bone marrow and peripheral blood	2 years	In vivo (bone marrow and peripheral blood) quantity of CD123 CAR copies were determined by means of qPCR
Progress-free survival(PFS) of CD123 CAR-T treatment in patients with refractory/relapsed acute myeloid leukemia	2 year	PFS will be assessed from the first CAR-T cell infusion to death from any cause or the first assessment of progression (censored)
Overall survival(OS) of CD123 CAR-T treatment in patients with refractory/relapsed acute myeloid leukemia	2 years	OS will be assessed from the first CAR-T cell infusion to death from any cause (censored)

Trial Locations

Locations (1)

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