- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05548088
LILRB4 STAR-T Cells in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
An Exploratory Clinical Study on the Safety and Efficacy of LILRB4 STAR-T Cells in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: xiangyu Zhao
- Phone Number: 010-88325949
- Email: zhao_xy@bjmu.edu.cn
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Aged 18-70 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;
- The subjects voluntarily joined the study, signed the informed consent form, had good compliance, and cooperated with the follow-up.
Exclusion Criteria:
- 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).
- Those with mental illness or history of drug abuse.
- Pregnant or breastfeeding subjects.
- The investigator believes that there are other factors that are not suitable for inclusion or that affect subjects participating in or completing the 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)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: LILRB4 STAR-T cells
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#6E6#1E7 cells/kg.
|
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, -4and-3followed by infusion of STAR-T cells.
STAR-T cells will be intravenously infused with a escalated dose of 1E6#3E6#6E6#1E7 cells/kg。
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluate safety and tolerability
Time Frame: 12 months
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Autitumor efficacy
Time Frame: 12 months
|
After infusion of LILRB4 STAR-T cells, the subjects underwent bone marrow puncture every month to evaluate the tumor load in the bone marrow.
The efficacy evaluation included complete morphological remission, complete remission with incomplete recovery of blood cytology, and partial remission.
|
12 months
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Xiangyu Zhao, PEKING UNICERSITY PEOPLE'S HOSPITAL
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- YTS104-002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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