Leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute
Conditions
Keywords
Leukemia, Acute Myeloid Leukemia, CD123, CAR-T
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.
Interventions
BIOLOGICALCD123 CAR-T cells
A single infusion of CD123-CAR-T cells will be administered intravenously
Sponsors
Chongqing Precision Biotech Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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) |
| 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 |
Countries
China
Contacts
Primary ContactZhi Yang, PhD
Backup ContactYingzi Zhang
Outcome results
None listed