CD123-Targeted CAR-T Cell Therapy for Relapsed/Refractory Acute Myeloid Leukemia

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.

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Yunnan
    • Kunming, Yunnan, China
      • Recruiting
      • 920th Hospital of Joint Logistics Support Force

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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; CD123 CAR-T cell therapy

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 AML 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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cellular kinetics of CD123 CAR-T in Blood	In vivo (peripheral blood) rate and quantity of CD123 CAR-T cells were determined by means of flow cytometry and qPCR	2 years
Cellular kinetics of CD123 CAR-T in Bone marrow	In vivo (bone marrow) rate and quantity of CD123 CAR-T cells were determined by means of flow cytometry and 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
Duration of Response (DOR) of CD123 CAR-T treatment in patients with refractory/relapsed AML	DOR will be assessed from the first assessment of CR or 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 AML	PFS will be assessed from the first CAR-T cell infusion to death from any cause or the first assessment of progression (censored)	2 years
Overall survival(OS) of CD123 CAR-T treatment in patients with refractory/relapsed AML	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): September 1, 2019
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: January 31, 2020
• First Submitted That Met QC Criteria: February 9, 2020
• First Posted (Actual): February 12, 2020

Study Record Updates

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

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: PBC011

Drug and device information, study documents

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