A Study of YTS109 Cell Injection in Subjects With Relapsed/Refractory Autoimmune Hemolytic Anemia

The Safety and Efficacy of YTS109 Cell Injection for Relapsed/Refractory Autoimmune Hemolytic Anemia Patients After Receiving Three or More Lines of Therapy.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Autoimmune Hemolytic Anemia; Anti-CD19 STAR T-cell Therapy; Failure ≥3 Lines of Therapies
• Intervention / Treatment: Biological: YTS109

• Study Type: Interventional
• Enrollment (Estimated): 7
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lele Zhang, PhD; Phone Number: 13752253515; Email: zhanglele@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YTS109; Participants will receive YTS109 cell infusion after preconditioning, and they need to be closely monitored for 24 hours following START-T cell infusion.	Biological: YTS109; In this study, subjects will receive YTS109 Cell Injection(0.5-1E6 STAR+T cell/kg) once.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity		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.	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.	Within 12 weeks after infusion
Objective response rate (ORR) of each dose group		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	Within 6 months after infusion

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Collaborators: China Immunotech (Beijing) Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): January 16, 2025
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: January 7, 2025
• First Submitted That Met QC Criteria: January 7, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 7, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Relapsed/Refractory Autoimmune Hemolytic Anemia; CD19-STAR T cells
• Additional Relevant MeSH Terms: Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: YTS109-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No