Clinical trial NCT04265963: CD123-Targeted CAR-T Cell Therapy for Relapsed/Refractory Acute Myeloid Leukemia
Official title: CD123-Targeted CAR-T Cell Therapy for Relapsed/Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lead sponsor: Chongqing Precision Biotech Co., Ltd
Sponsor class: INDUSTRY
First posted: 2020-02-12
Enrollment: 45
Sex: ALL
Minimum age (years): 2
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: There are limited options for treatment of relapse/refractory acute myeloid leukemia (AML). CD123 CAR-T cells may have an attractive and permanent effect on anti-tumor. This study purpose to estimate the safety and efficiency of CD123 CAR-T cells to patients with relapse/refractory AML.

Detailed description: CD123 is expressed on most myeloid leukemia cells so it is a 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 Acute Myelocytic 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 AML, and meet one of the following conditions：

   1. With persistent disease after at least two lines of therapy；
   2. Relapse to the last line of therapy in 6 months，as known as early recurrence;
   3. Relapse to the last line of therapy after 6 months, but refractory to this last line of therapy；
   4. Relapse more than once. The definition of relapse: Reappearance of blasts in the blood or bone marrow (\>5%) or in any extramedullary site after a CR (the most common are CNS and testicular leukemia).
3. Evidence for cell membrane CD123 expression;
4. KPS\>60;
5. The expect time of survive is above 3 months;
6. Ages: 2 to 75 years;
7. All genders;
8. The patients that diagnosis as high risks, relapse/refractory or inconformity criteria to other therapy；
9. No serious mental disorders;
10. Left ventricular ejection fraction ≥40%;
11. Sufficient hepatic function defined by ALT/AST\<5 x ULN and bilirubin≤34.2μmol/L;
12. Sufficient renal function defined by creatinine clearance \<220μmol/L;
13. Sufficient pulmonary function defined by indoor oxygen saturation≥92%;
14. No other illness may conflict with the protocol (e.g. autoimmune diseases, immune deficiency and organ transplantation；
15. Ability and willingness to adhere to the study visit schedule and all protocol requirements.

Exclusion Criteria:

1. Previous history of other malignancy;
2. Presence of uncontrolled active infection;
3. Evidence of disorder that need the treatment by glucocorticoids;
4. Active or chronic GVHD；
5. The patients treatment by inhibitor of T cell；
6. Pregnant or breasting-feeding women;
7. Any situation that investigators regard not suitable for attending in this study (e.g. HIV , HCVinfection or intravenous drug addiction) 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 AML that treatment by CD123 CAR-T cells therapy
timeFrame: 2 years
Secondary outcomes:
measure: Cellular kinetics of CD123 CAR-T in Blood
timeFrame: 2 years
measure: Cellular kinetics of CD123 CAR-T in Bone marrow
timeFrame: 2 years
measure: Cellular kinetics of CD123 positive cells in Bone marrow
timeFrame: 1 years
measure: Duration of Response (DOR) of CD123 CAR-T treatment in patients with refractory/relapsed AML
timeFrame: 2 years
measure: Progress-free survival(PFS) of CD123 CAR-T treatment in patients with refractory/relapsed AML
timeFrame: 2 years
measure: Overall survival(OS) of CD123 CAR-T treatment in patients with refractory/relapsed AML
timeFrame: 2 years
Other outcomes:
Locations:
city: Kunming
country: China
facility: 920th Hospital of Joint Logistics Support Force
state: Yunnan
Study officials:
affiliation: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
name: Sanbin Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chongqing University Cancer Hospital
name: Cheng Qian, PhD
role: PRINCIPAL_INVESTIGATOR
References: