Clinical Study on Safety and Efficacy of Anti-CLL1 /+CD33 CAR T Cells in the Treatment of Acute Myeloid Leukemia

Safety and Efficacy of Anti-CLL1 /+CD33 CAR T Cells in Refractory/Recurrent Acute Myeloid Leukemia: a Single-arm, Non-blind Clinical Study

This is a single-center, single-arm, open, intravenous drug administration of the safety and efficacy of clinical study.

Study Overview

• Status: Withdrawn
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Biological: CLL1/+CD33 CAR-T

Detailed Description

The primary objective of the clinical trial was to evaluate the safety and efficacy of single dose infusion of anti-CLL1 /+CD33 CAR T cells in patients with refractory/recurrent acute myeloid leukemia. A total of about 5 patients with refractory/recurrent acute myeloid leukemia were enrolled in this study, and the target dose range was 1.00~2.50x10^6/kgCAR-positive T cells.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350005
      • Fujian Provincial Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The patient or his/her legal guardian volunteers for the trial and signs an informed consent form;
2. Age range 1-18 years;
3. Acute myeloid leukemia (AML) with CLL1 and CD33 markers (including secondary patients) was diagnosed by pathology, histology and flow cytometry, or complete hematologic remission could not be achieved after 1 course of chemotherapy for hematologic relapse after drug withdrawal ;
4. The main organ functions of the patients were good: (1) liver function: ALT/AST < 3 times the upper limit of normal (ULN) and bilirubin ≤34.2 μmol/l; (2) renal function: creatinine < 220 μmol/l; (3) lung function: oxygen saturation ≥95% ; (4) cardiac function: left ventricular ejection fraction (LVEF)≥40% ;
5. The blood flow of peripheral superficial vein was unobstructed, which could meet the demands of intravenous drip and mononuclear cell collection;
6. ECOG score was 0-2.

Exclusion Criteria:

1. The patients had uncontrollable infectious diseases within 4 weeks before the enrollment;
2. Active hepatitis B/C virus;
3. HIV infection, treponema syphilis positive patients;
4. Pathological diagnosis of primary tumors other than acute myeloid leukemia;
5. Suffering from serious autoimmune diseases or immunodeficiency diseases;
6. The patient is allergic to antibodies or cytokines and other macromolecular biological drugs;
7. Pregnant or lactating women;
8. Patients who were considered ineligible for study for other reasons.

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: CLL1/+CD33 CAR-T; The target dose range for subjects was set to be 1.00~2.50x10^6/kg CAR-positive T cells.	Biological: CLL1/+CD33 CAR-T; CLL1/+CD33 CAR T is a type of CAR T cell therapy for patients with treating/relapsed acute myeloid leukemia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cytokine level after CLL1/+CD33 CAR-T infusion	Calculate the change of cytokine level in peripheral blood by flow cytometry after CAR-T infusion.	CAR T cell infusion before and 12 months after infusion
The change characteristics of chimeric antigen receptor(CAR)-T cell number in patients after infusion.	Track CAR-T cells expansion in patients after infusion by flow cytometry	CAR T cell infusion before and 12 months after infusion
The change characteristics of chimeric antigen receptor(CAR)-T cell copy number in patients after infusion.	Track CAR-T cells expansion in patients after infusion by Real-time Quantitative Polymerase Chain Reaction（qPCR）	CAR T cell infusion before and 12 months after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival	Counting from the beginning of cell transfusion until treatment failure, recurrence, or death (various causes). Subjects without any of these events were counted up to the last follow-up examination date. For patients without CR or CRi, EFS is calculated from the beginning of cell transfusion until disease progression or death. Based on the initial event.	Up to 12 months after CLL1/+CD33 CAR-T infusion
Overall survival	Death from any cause from the beginning of cell transfusion	Up to 12 months after CLL1/+CD33 CAR-T infusion
Duration of Overall Response	The time from the start of cell infusion when CR or PR is first achieved to disease progression.	Up to 12 months after CLL1/+CD33 CAR-T infusion
MRD negative rate	The rate of MRD negative subjects was determined by flow cytometry.	Up to 12 months after CLL1/+CD33 CAR-T infusion

Collaborators and Investigators

• Sponsor: Guangzhou Bio-gene Technology Co., Ltd
• Investigators: Principal Investigator: Hui Zhang, doctor, Children's Hospital of Fujian Province

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2023
• Primary Completion (Actual): August 28, 2023
• Study Completion (Actual): August 28, 2023

Study Registration Dates

• First Submitted: June 9, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 13, 2023

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: AML; CLL1; CD33
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: BG-CT-21-001

Drug and device information, study documents

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