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

Official title

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

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 STAR-T cell therapy in patients with autoimmune hemolytic anemia who have failed ≥3 lines of therapy. The objective is to evaluate the safety, preliminary efficacy, pharmacokinetics/pharmacodynamics (PK/PD), and immune cell reconstitution characteristics of YTS109 cell therapy in Multi-rAIHA subjects who have failed third-line or higher-line treatments. This study will also conduct an exploratory investigation into the impact of non-lymphodepleting conditioning prior to the infusion of STAR-T cells. For the non-lymphodepleting exploratory cell infusion, it can be administered as a single infusion or divided into 1 to 3 infusions (with the fractionated infusions to be completed within 7 days (and in any case no later than 15 days)). Dose escalation will commence at 1E6 cells/kg or the starting dose may be adjusted based on accumulated data.

Detailed description

Not provided

Interventions

• Drug YTS109 cell
  Subjects will receive YTS109 cell, and dose escalation will commence at 1E6 cells/kg or the starting dose may be adjusted based on accumulated data.

Primary outcome measures

• • Dose Limiting Toxicity [Time Frame: Within 28 days after infusion] [Time frame: Within 28 days]
• • The incidence and frequency of treatment-emergent adverse events [Time Frame: Within 6 months after infusion] [Time frame: Within 6 months]

Secondary outcome measures (7)

• • Best overall response rate (BOR) of each dose group [Time Frame: Within 12 weeks after infusion] [Time frame: Within 12 weeks]
• • Objective response rate (ORR) of each dose group [Time Frame: Within 4 weeks after infusion] [Time frame: Within 4 weeks]
• • Time to response (TTR) [Time Frame: Within 6 months after infusion] [Time frame: Within 6 months]
• • Peak Plasma Concentration (Cmax) of YTS109 To evaluate the metabolic characteristics of YTS109 [Time frame: Within 12 months after infusion]
• • Time to Peak (Tmax) of YTS109 To evaluate the metabolic characteristics of YTS109 [Time frame: Within 12 months after infusion.]
• • Area under the plasma concentration versus time curve (AUC) of YTS109 To evaluate the metabolic characteristics of YTS109 [Time frame: Within 12 months after infusion.]
• • The reconstitution of B cell in peripheral blood Changes in B cells quantification and phenotypic in peripheral blood [Time frame: Within 12 months after infusion.]

Eligibility criteria

Inclusion criteria

• Age ≥18 years, regardless of gender.
• A definitive diagnosis of Autoimmune Hemolytic Anemia (AIHA) or Evans Syndrome \[including warm antibody-type, mixed warm-cold antibody-type, and cold antibody-type hemolytic anemia (cold agglutinin disease)\] has been established, with diagnostic criteria referenced from the Chinese Clinical Practice Guidelines for the Diagnosis and Treatment of Autoimmune Hemolytic Anemia in Adults (2023 Edition).
• Patients who have undergone at least three failed treatment attempts, whose anemia symptoms (hemoglobin < 100 g/L) persist despite conventional therapy, and who remain unresponsive or experience recurrence after disease remission. Definition of Conventional Therapy: Treatment with glucocorticoids and/or rituximab, combined with any one or more of the following interventions: splenectomy, cyclosporine, cyclophosphamide, azathioprine, mycophenolate mofetil, bendamustine, fludarabine, bortezomib, or other pharmacological agents, as well as biologic agents including anti-CD38 monoclonal antibodies, BTK inhibitors, Syk inhibitors, complement inhibitors, etc.
• Adequate Organ Function:

• Liver Function:

Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN); Total bilirubin ≤ 2.0 × ULN (excluding Gilbert syndrome, where total bilirubin ≤ 3.0 × ULN).

• Renal Function:

Creatinine clearance (CrCl) ≥ 60 ml/minute (calculated using the Cockcroft-Gault formula).

• Oxygen Saturation (SpO₂): ≥ 92%.
• Bone Marrow Function Requirements:

• Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L;
• Platelet count ≥ 30 × 10⁹/L;
• International normalized ratio (INR) ≤ 1.5 × ULN;
• Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07287930 · YTS109-011

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗