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
Overview
- Phase
- Phase 1
- Intervention
- LILRB4 STAR-T cells
- Conditions
- Not specified
- Sponsor
- Peking University People's Hospital
- Enrollment
- 11
- Locations
- 2
- Primary Endpoint
- Evaluate safety and tolerability
- Status
- Completed
- Last Updated
- last year
Overview
Brief 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.
Investigators
Xiangyu Zhao
associate professor
Peking University People's Hospital
Eligibility Criteria
Inclusion Criteria
- •(A) 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;
- •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.
- •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;
Exclusion Criteria
- Not provided
Arms & Interventions
LILRB4 STAR-T cells
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.
Intervention: LILRB4 STAR-T cells
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Describe preliminaryefficacy of LILRB4 STAR-T cells(12 months)
- Rate of morphologic complete remission (CR)(12 months)