Relapsed/Refractory Acute Myeloid Leukemia and Chronic Granulocytic-Mononocytic LeukemiaPhase 1NCT05548088
LILRB4 STAR-T Cells in the Treatment of R/R AML/CMML
A Phase 1 study testing LILRB4 STAR-T cells in people with Relapsed/Refractory Acute Myeloid Leukemia and Chronic Granulocytic-Mononocytic Leukemia, run by Peking University People's Hospital at 2 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Relapsed/Refractory Acute Myeloid Leukemia and Chronic Granulocytic-Mononocytic Leukemia
- What is being tested?
- LILRB4 STAR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 2 sitesChina
- Study dates
- 25 May 2023to 3 Aug 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Subjects must meet all of the following enrollment criteria to be enrolled in this study.
- Age ≥ 18 years,≤ 60 years and gender;
- 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;
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- 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.
- ECOG score 0-2;
- Bone marrow samples were positive for LILRB4 (flow-through assay);
- Good organ function:
- Liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN), alanine transaminase (AST), alanine transaminase (ALT) ≤ 3 x ULN; Renal function: serum creatinine (Cr) ≤ 1.5 x ULN or creatinine clearance (Cockcroft-Gault formula) ≥ 60 mL/min; Cardiac function: left ventricular ejection fraction (LVEF) ≥50%; Pulmonary function: defined as ≤ grade 1 dyspnea and oxygen saturation > 92%.
- Female subjects of childbearing age or male subjects whose partner is a woman of childbearing age agree to use an effective method of contraception throughout the trial and for 12 months after cell infusion;
- Subjects voluntarily enrolled in the study, signed an informed consent form, were compliant, and cooperated with follow-up visits.
- The provider must fulfill the following conditions:
- Age greater than or equal to 12 years;
- HLA mating types are at least hemi-compatible;
- Adequate venous access is available for peripheral blood leukocyte isolation;
- Voluntary written informed consent.
Who cannot join
- Subjects who meet any of the following criteria are not eligible for enrollment in this study
- 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;
- 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;
- 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;
- 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.);
- 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;
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- Patients with current or previous history of CNS disorders such as seizures, stroke, severe brain injury aphasia, paralysis, dementia, Parkinson's disease, psychiatric disorders;
- Those with active central nervous system leukemia (CNSL) present at screening;
- History of solid organ transplantation or hematopoietic stem cell transplantation (HSCT) within 6 months prior to screening;
- Those with acute or chronic graft-versus-host disease (GVHD) at screening;
- Use of patients who have had any of the following medications or treatments performed within the designated time period prior to single-take:
- Have used any immunosuppressant within 2 weeks prior to single harvesting;
- Received any chemotherapy or small molecule targeted therapy within 2 weeks or 3 half-lives (whichever is shorter) prior to monoacquisition;
- Received any large molecule therapy such as monoclonal antibody, antibody coupled drug (ADC), or doublet within 4 weeks or 3 half-lives (whichever is shorter) prior to monoacquisition;
- People with mental illness, or a history of substance abuse;
- Pregnant or lactating subjects;
- Other factors that, in the opinion of the investigator, make enrollment inappropriate or affect the subject's participation in or completion of the study.
- Donor exclusion criteria
- Any of the following points are used as provider/third party exclusion criteria:
- A history of mental disorder that may interfere with compliance with the program or prevent signing the informed consent form;
- History of uncontrollable high blood pressure with medication, stroke or severe heart disease;
- There is anemia or thrombocytopenia;
- HBsAg-positive, or HBcAb-positive and peripheral blood HBV DNA-positive; HCV-antibody-positive individuals and HCV RNA-positive; syphilis spirochete antibody-positive; HIV antibody-positive;
- Presence or suspicion of uncontrolled fungal, bacterial, viral or other infections;
- Pregnancy;
- Any other circumstances that the investigator deems inappropriate as a donor/third party.
Trial locations and contacts
2 sites in 1 country.
China2 sites
Peking Unicersity People'S Hospital
Beijing, Beijing Municipality, 100044
Peking University People's Hospital
Beijing, Beijing Municipality, 100044
About this study
Official title: 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
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.
Read the 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.
- Being tested
- LILRB4 STAR-T cells
- Keywords
- LILRB4 STAR-T cells
- Medical subject headings
- Recurrence, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LILRB4 STAR-T cellsBiological
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
| Study group | Role | What they receive |
|---|---|---|
| LILRB4 STAR-T cells | Experimental | The subjects met the inclusion criteria, then collect the Lymphocytes and transfected with lentivirus to obtain LILRB4 STAR-T cells. The subjects were given fludarabine and cyclophosphamide chemotherapy 5 days before and 3 days after cell reinfusion. After two days of rest, the cells were reinjected at doses of 1E6,3E6,6E6,and 1E7/kg. Receives: Biological: LILRB4 STAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (6)
Describe preliminaryefficacy of LILRB4 STAR-T cells
Duration of Response (DOR)
Measured: 12 months
Rate of morphologic complete remission (CR)
Bone marrow blasts < 5%, absence of blasts with Auer rods, absence ofextramedullary disease; absolute neutrophil count >1.0G/L(1000/uL); plateletcount >100 xG/L(100.000/uL);independence of red cell transfusions.
Measured: 12 months
Describe preliminaryefficacy of LILRB4 STAR-T cells
Overall Survival (OS)
Measured: 12 months
Describe preliminaryefficacy of LILRB4 STAR-T cells
Overall response rate
Measured: 12 months
Describe preliminaryefficacy of LILRB4 STAR-T cells
Recurrence free survival（RFS）
Measured: 12 months
Describe preliminaryefficacy of LILRB4 STAR-T cells
Event-free lifetime（EFS）
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2022
- Study start25 May 2023
- Primary completion3 Aug 2024
- Study completion3 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory Acute Myeloid Leukemia and Chronic Granulocytic-Mononocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Peking University People's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peking University People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Bristar Immunotech Limited
- Responsible party
- Principal investigator, Xiangyu Zhao, Peking University People's Hospital
- Investigators
- Xiangyu Zhao, Principal investigator, PEKING UNICERSITY PEOPLE'S HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05548088
- Sponsor's protocol ID
- YTS104-002
- Status last verified
- Feb 2025
- First submitted
- 16 Sep 2022
- Last updated
- 5 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05548088
- Acronym / sponsor ID
- YTS104-002
- Keywords
- LILRB4 STAR-T cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Peking University People's HospitalUniversity, hospital or other
- Collaborators
- Bristar Immunotech Limited
- Study start
- 25 May 2023 (actual)
- Primary completion
- 3 Aug 2024 (actual)
- Study completion
- 3 Aug 2024 (actual)
- First posted
- 21 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LILRB4 STAR-T cells | Experimental | Biological: LILRB4 STAR-T cellsThe subjects met the inclusion criteria, then collect the Lymphocytes and transfected with lentivirus to obtain LILRB4 STAR-T cells. The subjects were given fludarabine and cyclophosphamide chemotherapy 5 days before and 3 days after cell reinfusion. After two days of rest, the cells were reinjected at doses of 1E6,3E6,6E6,and 1E7/kg. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (20 listed)
- Subjects must meet all of the following enrollment criteria to be enrolled in this study.
- Age ≥ 18 years,≤ 60 years and gender;
- 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):
- 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.
- ECOG score 0-2;
Key exclusion criteria (26 listed)
- Subjects who meet any of the following criteria are not eligible for enrollment in this study
- 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;
- 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;
- 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;
- 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.);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LILRB4 STAR-T cellsSubjects 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 | Biological | LILRB4 STAR-T cells |
Primary outcome
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.
6 secondary outcomes
Describe preliminaryefficacy of LILRB4 STAR-T cells
Time frame: 12 months
Rate of morphologic complete remission (CR)
Time frame: 12 months
Describe preliminaryefficacy of LILRB4 STAR-T cells
Time frame: 12 months
Describe preliminaryefficacy of LILRB4 STAR-T cells
Time frame: 12 months
Describe preliminaryefficacy of LILRB4 STAR-T cells
Time frame: 12 months
Describe preliminaryefficacy of LILRB4 STAR-T cells
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2025.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiangyu Zhao principal investigator
PEKING UNICERSITY PEOPLE'S HOSPITAL
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LILRB4 STAR-T cells in people with Relapsed/Refractory Acute Myeloid Leukemia and Chronic Granulocytic-Mononocytic Leukemia, run by Peking University People's Hospital at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate safety and tolerability (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2025.