LILRB4 STAR-T Cells in the Treatment of R/R AML/CMML

An Exploratory Clinical Study of the Safety and Efficacy of LILRB4 STAR-T Cells for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia/Chronic Granulocytic-Mononocytic Leukemia

NCT05548088•Peking University People's Hospital

View on ClinicalTrials.gov

Summary

This study is an exploratory study to evaluate the safety, tolerability, and efficacy of LILRB4 STAR-T cells in relapsed and refractory acute myeloid leukemia/Chronic Granulocytic-Mononocytic Leukemia subjects.

Detailed Description

This study will recruit LILRB4 positive AML/Chronic Granulocytic-Mononocytic Leukemia subjects,and Subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -5, -4 and -3 followed by infusion of LILRB4 STAR-T cells. LILRB4 STAR-T cells will be intravenously infused with a escalated dose of 1E6, 3E6, 6E6, 1E7 cells/kg.Safety and efficacy of LILRB4 STAR-T cells therapy will be monitored.The primary endpoint of the study is to observe DLT, AE, SAE, CRS and ICANS. Secondary objectives are to observe the efficacy of LILRB4 STAR-T cells, including Disease response, CR rate, ORR, RFS, EFS, OS, PK, PD and ADA.

Eligibility

Age

18 - 60 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•(A) Subjects must meet all of the following enrollment criteria to be enrolled in this study.
•1. Age ≥ 18 years,≤ 60 years and gender;
•2. Patients with acute myeloid leukemia or chronic granulomonocytic leukemia; 1) Patients with acute myeloid leukemia (AML) diagnosed according to the World Health Organization (WHO) 2016 criteria and who should meet any of the following relapsed-refractory (R/R) AML according to the Chinese Guidelines for the Diagnosis and Treatment of Relapsed-Refractory Acute Myeloid Leukemia (2021 Edition):
•* Primary patients who have failed 2 courses of treatment with a standard regimen (containing cytarabine and an anthracycline or anthraquinone);
•* Those who relapsed within 12 months after complete remission (CR) with consolidation and intensive therapy;
•* Those who relapsed after 12 months but failed to respond to conventional treatment;
•* Those with 2 or more recurrences;
•* Those with persistent extramedullary leukemia. Note: Definition of relapse: reappearance of leukemic cells in the peripheral blood or \>5% of primitive cells in the bone marrow after CR (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or extraparenchymal infiltration of leukemic cells.
•2\) Chronic granulocytic-monocytic leukemia diagnosed according to the World Health Organization (WHO) 2016 Classification Criteria for Tumors of Hematopoietic and Lymphoid Tissues and the Chinese Guidelines for the Diagnosis and Treatment of Chronic Granulocytic-Mononocytic Leukemia (2021 edition), with relapse refractory defined as follows: at least 2 complete cycles of at least one treatment (e.g., demethylating drugs ) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) ) without achieving remission or relapse after remission.
•3. ECOG score 0-2;
+10 more criteria

Exclusion Criteria

•1. Patients who have used CAR-T cell therapy or any other therapeutic product such as gene transduction within 3 months of signing the informed consent, except for those with undetectable CAR-T or CAR-T below the lower limit of detection; or patients who have participated in an interventional clinical study of an antitumor drug within 4 weeks prior to signing the informed consent;
•2. Individuals with a history of any of the following cardiovascular diseases within 6 months prior to screening: (1) congestive heart failure (New York Heart Association \[NYHA\] class ≥III), myocardial infarction, unstable angina, congenital long QT syndrome, left anterior hemiblock (bifascicular block), coronary angioplasty, stenting, coronary/peripheral artery bypass grafting, cerebrovascular accident ( CVA), transient ischemic attack, or pulmonary embolism, allowing for asymptomatic right bundle branch block; (2) severe cardiac arrhythmias requiring treatment (e.g., sustained ventricular tachycardia, ventricular fibrillation, tip-twist ventricular tachycardia, etc.); and (3) suffering from uncontrolled hypertension (systolic blood pressure greater than 160 mmHg and/or diastolic blood pressure greater than 100 mmHg), a history of hypertensive crisis, or hypertensive encephalopathy;
•3. Hepatitis B surface antigen (HBsAg) positive, Hepatitis B core antibody (HBcAb) positive subjects with peripheral blood HBV DNA copy number higher than the limit of detection, Hepatitis C virus (HCV) antibody positive subjects with HCV RNA copy number higher than the limit of detection, and Syphilis spirochete antibody test positive subjects;
•4. Patients with known systemic lupus erythematosus, comorbid active or uncontrolled autoimmune diseases (e.g., Crohns disease, rheumatoid arthritis, autoimmune hemolytic anemia, etc.), and primary or secondary immunodeficiencies (e.g., HIV infection or severe infectious diseases, etc.);
•5. Pre-existing or concurrent other untreated malignancies of indolent control affecting the subject's long-term survival, except cured carcinoma in situ of the uterine cervix, non-invasive basal cell or squamous cell skin cancers, or other malignancies that have been radically treated with localized prostate cancer, or ductal carcinoma in situ after radical surgery, and that have remained free of recurrence for at least 5 years;
•6. Patients with current or previous history of CNS disorders such as seizures, stroke, severe brain injury aphasia, paralysis, dementia, Parkinson's disease, psychiatric disorders;
•7. Those with active central nervous system leukemia (CNSL) present at screening;
•8. History of solid organ transplantation or hematopoietic stem cell transplantation (HSCT) within 6 months prior to screening;
•9. Those with acute or chronic graft-versus-host disease (GVHD) at screening;
•10. Use of patients who have had any of the following medications or treatments performed within the designated time period prior to single-take:
+13 more criteria

Locations (2)

Peking Unicersity People'S Hospital

Beijing, Beijing Municipality, China

Peking University People's Hospital

Beijing, Beijing Municipality, China

Key Dates

Start Date

May 25, 2023

Primary Completion Date

August 3, 2024

Completion Date

August 3, 2024

Last Updated

March 5, 2025

Enrollment

ACTUAL participants

Conditions

Relapsed/Refractory Acute Myeloid Leukemia and Chronic Granulocytic-Mononocytic Leukemia

Interventions

LILRB4 STAR-T cells

BIOLOGICAL