Safety and Efficacy of Anti-CD123 CAR-T Therapy in Patients With Refractory/ Relapsed CD123+ Acute Myeloid Leukemia.

Phase 1

• Conditions: CD123+ Acute Myeloid Leukemia
• Interventions: Biological: Third-generation anti-CD123 CAR-T cells

• Registration Number: NCT04014881
• Lead Sponsor: Wuhan Union Hospital, China

Brief Summary

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia.

Detailed Description

CD123 is a transmembrane subunit of the IL-3 receptor expressed on AML blasts. The investigators have conducted a third generationCD123-targeted CAR containing CD137 and CD28 costimulatory domains.This study aims to evaluate the safety and efficacy of anti-CD123 CAR-T cells in patients with relapsed/refractory CD123+ Acute Myeloid Leukemia.

Study Timeline

• Study First Submitted: 2019-07-02
• Study Start: 2019-07-06
• Study First Submitted QC: 2019-07-08
• Study First Posted: 2019-07-10
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-05
• Last Update Posted: 2019-08-07
• Primary Completion: 2021-07-01
• Study Completion: 2022-07-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Pathological and histological examination confirmed CD123+ refractory or relapsed Acute Myeloid Leukemia.

   A. Diagnostic criteria for recurrent AML: After complete remission (CR), leukemia cells or bone marrow primordial cells > 0.050 (except for bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration appears again in peripheral blood.

   B．Diagnostic criteria for refractory AML(Meeting one of the following)

   i. ineffectiveness after the first standard regimen treatment of 2 courses.

   ii. patients relapse within 12 months after consolidation and intensive treatment after CR.

   iii. Patients relapse 12 months later and fail to respond to conventional chemotherapy.

   iv. Patients with two or more recurrences.

   v. Patients with persistent extramedullary leukemia.

   vi. Patients with recurrence after CR and unsuitable for HSCT (auto/allo-HSCT).

2. Aged 18 to 70 years (including 18 and 70 years old).

3. At least one measurable or evaluable lesion：AML patients with positive or relapsed positive bone marrow MRD.

4. ECOG≤ 2 and expected lifetime ≥3 months.

5. Adequate organ function:

   A. Liver function: ALT/AST≤3 ULN. Total bilirubin≤2 ULN.

   B. Renal function: eGFR> 60 mL/min/1.73 m2, or creatinine clearance ≥45mL/min.

   C. Lung function: Carbon Monoxide (DLCO) or Forced Expiratory Volume in the first second (FEV1) > 45% predicted.

   D. Cardiac function: LVEF ≥ 50%.

6. The patients did not receive any anticancer treatments such as chemotherapy, radiotherapy and immunotherapy (such as immunosuppressive drugs) within 4 weeks before admission, and the toxicity related to previous treatments had returned to < 1 level at admission (except for low toxicity such as alopecia).

7. Women of child-bearing potential and all male participants must use effective methods of contraception for at least 12 months after infusion.

8. Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria

1. Women who are pregnant (urine/blood pregnancy test positive) or lactating.
2. Male or female with a conception plan in the past 1 years.
3. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment.
4. Uncontrolled infectious disease within 4 weeks prior to enrollment.
5. Active hepatitis B/C virus.
6. HIV infected patients.
7. Suffering from a serious autoimmune disease or immunodeficiency disease.
8. The patient is allergic and is allergic to macromolecular biopharmaceuticals such as antibodies or cytokines.
9. The patient participated in other clinical trials within 6 weeks prior to enrollment.
10. Systemic use of hormones within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids).
11. Suffering from mental illness.
12. Patient has drug abuse/addiction.
13. Central nervous system involvement.
14. According to the investigator's judgment, the patient has other unsuitable grouping conditions.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD123+ Acute Myeloid Leukemia	Third-generation anti-CD123 CAR-T cells	Patients will receive CD123-targeted CAR-T cells in the dose-climbing trial. Each dose group has 3 patients and the the maximum dose can be extended.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-related Adverse Events	3 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 4.0).

Secondary Outcome Measures

Name	Time	Method
Overall survival(OS) of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia	3 years	OS will be assessed from the first CAR-T cell infusion to death or last follow-up (censored).
Duration of Response(DOR) of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia	3 years	DOR will be assessed from the first CAR-T cell infusion to death or last follow-up (censored).
Progress-free survival(PFS) of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia	3 years	PFS will be assessed from the first CAR-T cell infusion to death or last follow-up (censored).
Overall remission rate(ORR) of anti-CD123 CAR-T Therapy in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia	3 years	ORR will be assessed from the first CAR-T cell infusion to death or last follow-up (censored).
Rate of anti-CD123 CAR-T cells in bone marrow cells and peripheral blood cells	3 years	In vivo (bone marrow and peripheral blood) rate and quantity of anti-CD123 CAR-T cells were determined by means of flow cytometry.
Quantity of anti-CD123 CAR copies in bone marrow cells and peripheral blood cells	3 years	In vivo (bone marrow and peripheral blood) quantity of anti-CD123 CAR copies were determined by means of qPCR.

Trial Locations

Locations (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China