Safety and Efficacy of CD123-Targeted CAR-T Therapy for Relapsed/Refractory Acute Myeloid Leukemia
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: CD123 CAR-T cells treat Patients will be be treated with CD123 CAR-T cells |
Biological: CD123 CAR-T cells
A single infusion of CD123-CAR-T cells will be administered intravenously
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Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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
- 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)
- 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)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Signed written informed consent;
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Diagnose as relapsed /refractory acute myeloid leukemia, and meet one of the following conditions:
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Failed to standard chemotherapy regimens;
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Relapse after complete remission, high-risk and / or refractory patients ;
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Relapse after hematopoietic stem cell transplantation;
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Evidence for cell membrane CD123 expression;
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All genders, ages: 3 to 75 years;
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The expect time of survive is above 12 weeks;
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KPS>60;
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No serious mental disorders ;
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Left ventricular ejection fraction ≥50%
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Sufficient hepatic function defined by ALT/AST≤3 x ULN and bilirubin≤2 x ULN;
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Sufficient renal function defined by creatinine clearance≤2 x ULN;
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Sufficient pulmonary function defined by indoor oxygen saturation≥92%;
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With single or venous blood collection standards, and no other cell collection contraindications;
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Ability and willingness to adhere to the study visit schedule and all protocol requirements.
Exclusion Criteria:
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Have received CAR-T therapy or other genetically modified cell therapy before screening;
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Participated in other clinical research within 1 month before screening;
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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;
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Live attenuated vaccine within 4 weeks before screening;
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Convulsion or stoke within past 6 months;
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Previous history of other malignancy;
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Presence of uncontrolled active infection;
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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;
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Pregnant or breasting-feeding women;
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Any situation that investigators regard not suitable for attending in this study or may affect the data analysis.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Chongqing University Cancer Hospital | Chongqing | Chongqing | China |
Sponsors and Collaborators
- Chongqing Precision Biotech Co., Ltd
Investigators
- Principal Investigator: Cheng Qian, PhD, Chongqing University Cancer Hospital
- Principal Investigator: Ying Xiang, MD, Chongqing University Cancer Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PBC016