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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Leukemia, Myeloid, Acute, Leukemia, Leukemia, Myeloid

Intervention / Treatment
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* Biological: CD123 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent; Diagnose as relapsed /refractory acute myeloid leukemia, and meet one of the following conditions: Failed to standard chemotherapy regimens; Relapse after complete remission, high-risk and / or refractory patients ; Relapse after hematopoietic stem cell transplantation; Evidence for cell membrane CD123 expression; All genders, ages: 3 to 75 years； The expect time of survive is above 12 weeks; KPS>60； No serious mental disorders ; Left ventricular ejection fraction ≥50% Sufficient hepatic function defined by ALT/AST≤3 x ULN and bilirubin≤2 x ULN; Sufficient renal function defined by creatinine clearance≤2 x ULN; Sufficient pulmonary function defined by indoor oxygen saturation≥92%; With single or venous blood collection standards, and no other cell collection contraindications; Ability and willingness to adhere to the study visit schedule and all protocol requirements. Exclusion Criteria: Have received CAR-T therapy or other genetically modified cell therapy before screening； Participated in other clinical research within 1 month before screening； 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; Live attenuated vaccine within 4 weeks before screening; Convulsion or stoke within past 6 months; Previous history of other malignancy; Presence of uncontrolled active infection; 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; Pregnant or breasting-feeding women; Any situation that investigators regard not suitable for attending in this study or may affect the data analysis.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD123 CAR-T cells treat<br>Patients will be be treated with CD123 CAR-T cells | Biological: CD123 CAR-T cells<br>* A single infusion of CD123-CAR-T cells will be administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| Levels of cytokines in serum | In vivo (serum) quantity of cytokines | 3 months | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Acute Myeloid Leukemia, CD123, CAR-T