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

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.

Study Overview

• Status: Recruiting
• Conditions: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Intervention / Treatment: Biological: CD123 CAR-T cells

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 Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China
      • Recruiting
      • Chongqing University Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 71 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chongqing Precision Biotech Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: February 13, 2020
• First Submitted That Met QC Criteria: February 14, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 16, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; CAR-T; Leukemia; CD123
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: PBC016

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No