Clinical trial NCT04272125: Safety and Efficacy of CD123-Targeted CAR-T Therapy for Relapsed/Refractory Acute Myeloid Leukemia
Official title: Safety and Efficacy of CD123-Targeted CAR-T Therapy for Relapsed/Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Keywords: Leukemia
Acute Myeloid Leukemia
CD123
CAR-T
Lead sponsor: Chongqing Precision Biotech Co., Ltd
Sponsor class: INDUSTRY
First posted: 2020-02-17
Enrollment: 40
Sex: ALL
Minimum age (years): 3
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events that related to treatment
timeFrame: 2 years
measure: The response rate of CD123 CAR-T treatment in patients with relapse/refractory Acute Myeloid Leukemia that treatment by CD123 CAR-T cells therapy
timeFrame: 6 months
Secondary outcomes:
measure: Rate of CD123 CAR-T cells in bone marrow and peripheral blood
timeFrame: 2 years
measure: Quantity of CD123 CAR copies in bone marrow and peripheral blood
timeFrame: 2 years
measure: Cellular kinetics of CD123 positive cells in bone marrow
timeFrame: 1 years
measure: Levels of cytokines in serum
timeFrame: 3 months
measure: Duration of Response (DOR) of CD123 CAR-T treatment in patients with refractory/relapsed acute myeloid leukemia
timeFrame: 2 years
measure: Progress-free survival(PFS) of CD123 CAR-T treatment in patients with refractory/relapsed acute myeloid leukemia
timeFrame: 2 year
measure: Overall survival(OS) of CD123 CAR-T treatment in patients with refractory/relapsed acute myeloid leukemia
timeFrame: 2 years
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
Study officials:
affiliation: Chongqing University Cancer Hospital
name: Cheng Qian, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chongqing University Cancer Hospital
name: Ying Xiang, MD
role: PRINCIPAL_INVESTIGATOR
References: