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

Phase 1

Not yet recruiting

• Conditions: Autoimmune Hemolytic Anemia; Anti-CD19 STAR T-cell Therapy; Failure ≥3 Lines of Therapies
• Interventions: Biological: YTS109

• Registration Number: NCT06770504
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-07
• Study First Submitted QC: 2025-01-07
• Last Update Submitted: 2025-01-07
• Study First Posted: 2025-01-13
• Last Update Posted: 2025-01-13
• Study Start: 2025-01-16
• Primary Completion: 2025-12-30
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 7

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
YTS109	YTS109	Participants will receive YTS109 cell infusion after preconditioning, and they need to be closely monitored for 24 hours following START-T cell infusion.

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicity	Within 28 days after infusion
The incidence and frequency of treatment-emergent adverse events	Within 12 months after infusion	Safety assessments are conducted using the NCI-CTCAE version 5.0 standards.
Best overall response rate (BOR) of each dose group	Within 12 weeks after infusion	BOR is determined as the most favorable response observed after cell infusion, until either disease relapse or the completion of a specified observation period.
Objective response rate (ORR) of each dose group	Within 4 weeks after infusion
Time to response (TTR)	Within 6 months after infusion	TTR is defined as the duration from cell infusion to the achievement of a hematological response