LILRB4 STAR-T Cells in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

NCT05518357 | Completed Phase 1

• 1 other identifier: YTS104-001
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, single-arm, open-label phase I clinical study to determine the safety and efficacy of LILRB4 STAR-T cells in relapsed/refractory acute myeloid leukemia subjects.

Conditions

Relapsed/Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Evaluate safety and tolerability

  Subjects are observed for dose-limiting toxicity(DLT) after LILRB4 STAR-T cells infusion, with the recording of adverse events(AE) and serious adverse events(SAE), with a focus on cytokine release syndrome(CRS) and immune cell-associated neurotoxicity(ICANS).All of the AE ratings were assessed according to the CTCAE.

  12 months

Secondary Outcomes (1)

• Antitumor efficacy

  12 months

Study Arms (1)

LILRB4 STAR-T

EXPERIMENTAL

LILRB4 STAR-T cells are prepared via lentiviral infection. 5 days prior to infusion of STAR-T cells, subjects receive fludarabine at dose 25-30mg/m2/day and cyclophosphamide treatment at dose 250-300mg/m2 for 3 days and take a rest for 2 days before infusion. STAR-T cells will be intravenously infused with a escalated dose of 1E6#3E6#1E7 cells/kg

Biological: LILRB4 STAR-T

Interventions

LILRB4 STAR-T BIOLOGICAL

Subjects with relapsed/refractory acute myeloid leukemia will be enrolled in the study, and Subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -5, -4 and -3 followed by infusion of STAR-T cells. STAR-T cells will be intravenously infused with a escalated dose of 1E6#3E6#1E7 cells/kg。

LILRB4 STAR-T

Eligibility Criteria

• Age: 2 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 2-70 years, gender is not limited;
• Subjects diagnosed with AML according to WHO 2016 criteria and according to the "Chinese Guidelines for the Diagnosis and Treatment of Relapsed and Refractory Acute Myeloid Leukemia (2021 Edition)" should meet any of the following relapsed and refractory (R/R) AML patients:
• Patients who have failed two cycles of standard chemotherapy;
• Relapse within 12 months after consolidation and intensification therapy after complete remission (CR);
• Relapse after 12 months but failed to respond to conventional treatment
• two or more recurrences;
• persistent extramedullary leukemia；
• ECOG physical status level is 0 to 2;
• Bone marrow sample must be LILRB4 positive(Flow Cytometry)
• Major organs must meet the following criteria:
• Liver function: Total bilirubin≤1.5 times the upper limit of normal,ALT and AST≤3 times the upper limit of normal,
• Renal function:Creatinine≤1.5 times the upper limit of normal (ULN) or creatinine clearance rate ≥60ml/min,
• Cardiac function:LVEF≥50%，
• Lung function:Defined as ≤grade 1 dyspnea and blood oxygen saturation \>92%;
• Female subjects of reproductive age or male subjects whose partners are women of reproductive age agree to use an effective method of contraception throughout the trial and for 12 months after cell infusion;

You may not qualify if:

• Received CAR-T therapy or other gene-modified cell therapy in the past or participated in other clinical investigators within 1 month before screening;
• Any of the following cardiovascular and cerebrovascular diseases occurred within 6 months before screening:
• congestive heart failure(NYHA stage III),myocardial infarction,unstable angina pectoris,congenital long QT syndrom,Anterior left block,coronary angioplasty,stent implantation,Coronary/peripheral artery bypass grafting,CVA,Transient ischemic attack or pulmonary embolism,Asymptomatic right bundle branch block was allowed;
• Serious arrhythmias requiring treatment (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes, etc.);
• 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;
• The subject is positive for hepatitis B surface antigen or HBV DNA is higher than the detection limit of analysis method;Positive hepatitis C antibody or HCV RNA is higher than the detection limit of the analytical method;The subjects were positive for syphilis antibody;
• The subject with known systemic lupus erythematosus, active or uncontrolled autoimmune disease (such as Crohns disease, rheumatoid arthritis, autoimmune hemolytic anemia, etc.), primary or secondary immunodeficiency (such as HIV infection or serious infectious disease, etc.);
• Previous or concurrent other incurable malignancies with unstable control,Affect the long-term survival of subjects, except for cured cervical carcinoma in situ, non-invasive basal cell or squamous cell skin cancer or other local prostate cancer after radical treatment, ductal carcinoma in situ after radical resection and at least 5 Years without recurrence of malignant tumor;
• Subjects with current or previous history of central nervous system disease, such as seizures, stroke, severe brain injury, aphasia, paralysis, dementia, Parkinson's disease, mental illness, etc. or central nervous system leukemia (CNSL);
• Subjects with a history of solid organ transplantation or hematopoietic stem cell transplantation (HSCT) within 6 months prior to screening;
• Subjects with aGVHD and cGVHD at screening;
• Subjects who have had any of the following drugs or treatments within the specified time period prior to apheresis:
• Administered any immunosuppressant within 2 weeks prior to apheresis;
• Received any chemotherapy within 2 weeks or 3 half-lives, whichever is shorter, prior to apheresis;
• Received any macromolecule or small molecule targeted therapy such as monoclonal antibody, antibody-drug conjugate (ADC), double antibody, etc. within 4 weeks before apheresis or within 3 half-lives (whichever is shorter);

Sponsors & Collaborators

• Hebei Yanda Ludaopei Hospital: lead

Study Sites (1)

Hebei Yanda Ludaopei Hospital

Sanhe, Hebei, 065200, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Peihua Lu, MD/PHD

  HeiBei YanDa Ludaopei hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2022
• First Posted: August 26, 2022
• Study Start: June 24, 2022
• Primary Completion: November 15, 2022
• Study Completion: November 15, 2022
• Last Updated: January 12, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)