Clinical Study of Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of Myeloid Leukemia

Researchers plan to enroll a total of 100 patients with relapsed, refractory acute myeloid leukemia (AML) to receive a single dose of autologous CAR T cells.The safety of CAR T therapy was evaluated by observing adverse events after cell therapy;The efficacy of CAR-T therapy was evaluated against the outcome of patients' own past standard treatment regimens or historical data.Blood and bone marrow were collected before and 12 months after infusion to detect the number and activity of CAR T cells, and to evaluate the pharmacokinetics (PK) of CAR T cells.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Anti-CLL1 CART cells

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Wang Sanbin, Doctor; Phone Number: (86)13187424131; Email: Sanbin1011@163.com

Study Locations

• China
  • Yunnan
    • Kunming, Yunnan, China
      • Recruiting
      • No.212 Daguan Road, Xishan District

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. The diagnosis of myeloid leukemia was clear;Refractory treatment was defined as: (1) 2 patients who did not achieve partial remission after treatment with standard induced remission regimens.② The patients who relapsed within 6 months after the first remission were also called early recurrence.③ The failure relapsed 6 months after the initial response, but was retreated with the original induced response regimen.(4) multiple relapse.Relapse is defined as: patients who achieve complete remission after treatment, more than 5% of leukemia cells in the bone marrow, also known as intramedullary recurrence;Or the presence of leukaemia outside the bone marrow, also known as extramedullary relapse (usually in the central nervous system, testicular leukemia is the most common);
2. Diseased cells were confirmed to express CD123, CLL1 and other targets;
3. KPS > 60 points;
4. Expected survival of more than 3 months;
5. No gender limitation, age 2-75;
6. Patients clinically diagnosed as high-risk type, refractory type of recurrence or not eligible for standard treatment;
7. No serious mental disorders;
8. Sufficient heart, liver and renal function (a. Liver function: ALT/AST < 3 times upper limit of normal value (ULN) and bilirubin ≤34.2μmol/L;B. Renal function: creatinine < 220μmol/L;C. Lung function: indoor oxygen saturation ≥95%;D. Cardiac function: left ventricular ejection fraction (LVEF) ≥40%;);
9. No other serious diseases (such as autoimmune diseases, immune deficiency, organ transplantation) that are in conflict with this program;
10. Can cooperate with trial management and follow-up;
11. Patients voluntarily participated in the study and signed the informed consent

Exclusion Criteria:

1. History of other malignant tumors;
2. Uncontrolled active infection;
3. Patients with underlying diseases requiring systemic use of glucocorticoids;
4. Acute or chronic GVHD;
5. T-cell inhibitor therapy;
6. Pregnant and lactating women;
7. Patients with active hepatitis B;
8. Other conditions considered by the investigator to be inappropriate for the study (HIV infection, intravenous drug addiction, etc.), or other conditions that may affect the analysis of the results of the clinical study.

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: Single arm; CLL-1 targeting CAR-T treatment	Drug: Anti-CLL1 CART cells; In this study, patients with acute myeloid leukemia were treated with autologous anti-CLL1 CAR T cells by a single, intravenous infusion.Blood and bone marrow were collected before and 12 months after infusion to detect the number and activity of CAR T cells, and to evaluate the efficacy of CAR T cells.; Other Names: CLL1 CAR-T

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of AE after CAR-T infusion	Incidence of adverse events after CAR-T infusion Data. The records of adverse events (AE) should include: description of AE and all related symptoms, occurrence time, severity, duration, measures taken, final results and outcomes. According to NCI CTC AE 5.0 standard, AE was scored Grade. Safety evaluation indexes include but are not limited to the following contents; Any spontaneously reported and all directly observed adverse events;; Any abnormal changes in vital signs and physical examination;; The abnormal results of laboratory examination, physical examination and blood examination with clinical significance after treatment	up to 12 months after CAR-T infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR rate	Overall response rate (ORR=CR+CRi) after CAR-T infusion	1month, 2 months, 3months, 6months ,12months after CAR-T infusion
PFS	Progression free survival (PFS) after CAR-T infusion	1month, 2 months, 3months, 6months ,12months after CAR-T infusion
OS	overall survival (OS) after CAR-T infusion	1month, 2 months, 3months, 6months ,12months after CAR-T infusion
Change of CAR Copies	CAR Copies measured by qPCR after CAR-T infusion	Days 4, 7, 10, 14 and months 2, 3, 6, 9, 12 after Fast Dual CAR-T infusion
Change of CAR-T cell counts	CAR-T cell counts measured by Flow cytometry after CAR-T infusion	Days 4, 7, 10, 14 and months 2, 3, 6, 9, 12 after Fast Dual CAR-T infusion

Collaborators and Investigators

• Sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2021
• Primary Completion (Estimated): December 5, 2024
• Study Completion (Estimated): December 5, 2024

Study Registration Dates

• First Submitted: May 8, 2021
• First Submitted That Met QC Criteria: June 7, 2021
• First Posted (Actual): June 11, 2021

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid
• Other Study ID Numbers: BG-CT-19-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No