Hematologic Diseases, Neoplasms
Conditions
Keywords
IL-5 CAR-T, Eosinophil
Brief summary
This is an open-label, single-arm clinical study designed to evaluate the efficacy and safety of IL-5 CAR-T cell therapy in the treatment of patients with CD125-positive eosinophilic leukemia.
Detailed description
The IL-5 CAR is composed of full length human IL-5 (hIL-5) fused to the human CD8α hinge and transmembrane domains, followed by the human 4-1BB co-stimulatory domain and the CD3ζ signaling domain. Prior to CAR-T cell infusion, the patients will be subjected to preconditioning treatment. After CAR-T cell infusion, the patients will be evaluated for adverse reactions and efficacy. The Main research objectives: To evaluate the safety and efficacy of IL-5 CAR-T cells in patients with CD125-positive eosinophilic leukemia. The Secondary research objectives: To investigate the cytokinetic characteristics of IL-5 CAR-T cells in patients with CD125-positive eosinophilic leukemia.
Interventions
DRUGIL-5 CAR-T cells
Each subject receive IL-5 CAR T-cells by intravenous infusion
Sponsors
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1.Male or female patients aged ≥18 years; * 2.Diagnosis of eosinophilic leukemia (EL) established according to the WHO 2022 diagnostic criteria; * 3.Interleukin-5 receptor α (IL-5Rα, CD125) is expressed on ≥50% of leukemic blasts. * 4.Meet any of the following criteria for refractory/relapsed eosinophilic leukemia: * a) Inadequate response to standard therapy: failure to achieve complete remission (CR) after standard treatments (e.g., imatinib, corticosteroids, interferon-α, chemotherapy, etc.); * b) Disease progression/relapse within 6 months after achieving remission; * 5.Serum total bilirubin ≤1.5 × the upper limit of normal (ULN), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN; * 6.Left ventricular ejection fraction (LVEF) \>50% as assessed by echocardiography; * 7.Peripheral oxygen saturation (SpO₂) ≥92% on room air (without supplemental oxygen); * 8.Estimated life expectancy \>3 months; * 9.Eastern Cooperative Oncology Group (ECOG) performance status 0-1; * 10.Women and men of childbearing potential must agree to use appropriate, effective contraception prior to study entry, throughout the study period, and for 6 months after cell infusion (the safety of this therapy for unborn children is unknown and may pose potential risks); * 11.Patients who are willing to participate in this study and who are able to understand and voluntarily sign the written informed consent form.
Exclusion criteria
* 1.History of epilepsy or other central nervous system (CNS) disorders; * 2.Presence of any of the following:Hepatitis B surface antigen (HBsAg)-positive; Any of HBeAg, HBeAb, or HBcAb positive and detectable hepatitis B virus (HBV) DNA in peripheral blood above the lower limit of detection; Hepatitis C virus (HCV) antibody-positive; Human immunodeficiency virus (HIV) antibody-positive; Positive serologic test for syphilis; * 3.History of QT interval prolongation or severe cardiac disease; * 4.Presence of uncontrolled active infection; * 5.Any condition that, in the opinion of the investigator, may increase the risk to the subject or interfere with the interpretation of the study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | Up to 28 days after Treatment | Adverse events assessed according to NCI-CTCAE v5.0 criteria |
| Incidence of treatment-emergent adverse events (TEAEs) | Up to 2 years after Treatment | Incidence of treatment-emergent adverse events \[Safety and Tolerability\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response (CR), and complete response with incomplete hematologic recovery (CRi) | Up to 12 weeks after CAR-T infusion | The proportion of patients with CR (complete response) /CRi (complete response with incomplete blood cell recovery) and PR (partial response). |
| Duration of remission ,DOR | Up to 1 years after CAR-T infusion | The time from CR/CRi and PR to disease relapsed or death due to disease progression after CAR-T infusion |
| Overall survival, OS | Up to 1 years after CAR-T infusion | The time from CAR-T infusion to death due to any cause |
| Leukemia-Free Survival, LFS | Up to 2 years after Treatment | The time from CAR-T infusion torecurrence or metastasis |
Countries
China
Contacts
Primary ContactSongmin Ying, MD
Backup ContactYongxian Hu, MD
Outcome results
None listed