Institute of Hematology & Blood Diseases Hospital, China7 enrolled
Overview
This is a Phase I, single-arm, open-label, dose-escalation and dose-expansion study. The primary objective is to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of YTS109 START T-cell therapy in patients with autoimmune hemolytic anemia who have failed ≥3 lines of therapy.
In this study, subjects will receive YTS109 Cell Injection(0.5-1E6 STAR+T cell/kg) once.
Eligibility
Sex: ALLMin age: 12 Years
Medical Language ↔ Plain English
Inclusion Criteria:
* Age ≥12 years, regardless of gender.
* Diagnosis of AIHA or Evans syndrome \[including warm antibody, mixed AIHA and cold antibody AIHA (Cold agglutinin disease)\].
* Failure or intolerance to at least 3 lines of therapy: glucocorticoids and/or rituximab, and any one of the following treatments (splenectomy, cyclosporine, cyclophosphamide, azathioprine, mycophenolate mofetil, bendamustine, fludarabine, bortezomib, etc.Biologics, including anti-CD38 monoclonal antibody, BTK inhibitor, Syk inhibitor and complement inhibitor) (HGB \< 100g/L).
* Adequate organ function: a. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN. b. Creatinine clearance (CrCl) (Cockcroft-Gault formula) ≥60ml/min. c.Blood oxygen saturation (SpO2) ≥92%.
* ECOG performance status≤2
* Subjects of childbearing potential will be required to follow contraception requirements from the time of enrollment until the end of the 12-month safety follow-up period.
* The subjects voluntarily participate in the study, sign the informed consent, demonstrate good compliance, and cooperate with follow-up.
Exclusion Criteria:
* Diagnosis of lymphoproliferative tumor
* Other hereditary or acquired hemolytic diseases (Secondary AIHA caused by drugs or infection)
* The platelet count in peripheral blood\<30×10\^9/L
* Pregnant or breast-feeding subjects
* Receive any of the following treatments within the specified time before cell infusion: a.anti-CD20 monoclonal antibodies \<12 weeks, b.sutimlimab or other marketed biologics \<5 half-lives,c.plasma exchange \<4 weeks, d.post-splenectomy \<12 weeks, e. BTK inhibitors, anti-CD38 monoclonal antibody, Syk inhibitors, BAFF inhibitors \< 5 half-lives.
* Previously received organ or stem cell transplantation
* History of new thrombosis or organ infarction in the past 6 months
* Diagnosis of the active stage of the connective tissue disease.
* Have active infections, such as sepsis, bacteremia, fungemia, uncontrolled pulmonary infection and active tuberculosis, etc.
* Positive hepatitis B surface antigen (HBsAg) or hepatitis B e antigen (HBeAg); positive hepatitis B e antibody (HBe-Ab) or hepatitis B core antibody (HBc-Ab), and the HBV-DNA copy number is above the lower limit of the measurable capacity; positive hepatitis C (HCV) antibody; positive human immunodeficiency virus (HIV) antibody; positive syphilis test.
* Underwent major surgery within 4 weeks before screening, as determined by the investigator to be unsuitable for enrollment.
* Have malignant tumors within 5 years before enrollment, except tumors with negligible risk of metastasis or death and curable tumors, such as adequately treated cervical carcinoma in situ, cutaneous basal cell carcinoma, etc.
* Have any of the following cardiovascular diseases: a.Left ventricular ejection fraction (LVEF) ≤45%, b. presence of active heart disease or congestive heart failure (New York Heart Association \[NYHA\] Class III or IV)), c.severe arrhythmias requiring treatment, d.have myocardial infarction, bypass surgery, or stent placement within the 6 months before the study, e.other heart diseases judged by the researcher to be unsuitable for enrollment.
* Have a history of live attenuated vaccines within 6 weeks before enrollment.
* Have a history of epilepsy or other active central nervous system diseases.
* Have an allergy to the ingredients of the medicine used in this study.
* Previously received CAR-T cell therapy.
* Patients considered to be ineligible for the study by the investigator for reasons other than the above.
Outcomes
Primary Outcomes
Dose Limiting Toxicity
Time frame: Within 28 days after infusion
The incidence and frequency of treatment-emergent adverse events
Safety assessments are conducted using the NCI-CTCAE version 5.0 standards.
Time frame: Within 12 months after infusion
Best overall response rate (BOR) of each dose group
BOR is determined as the most favorable response observed after cell infusion, until either disease relapse or the completion of a specified observation period.
Time frame: Within 12 weeks after infusion
Objective response rate (ORR) of each dose group
Time frame: Within 4 weeks after infusion
Time to response (TTR)
TTR is defined as the duration from cell infusion to the achievement of a hematological response