Clinical trial NCT06770504: A Study of YTS109 Cell Injection in Subjects With Relapsed/Refractory Autoimmune Hemolytic Anemia
Official title: The Safety and Efficacy of YTS109 Cell Injection for Relapsed/Refractory Autoimmune Hemolytic Anemia Patients After Receiving Three or More Lines of Therapy.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Autoimmune Hemolytic Anemia
Anti-CD19 STAR T-cell Therapy
Failure ≥3 Lines of Therapies
Keywords: Relapsed/Refractory Autoimmune Hemolytic Anemia
CD19-STAR T cells
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: China Immunotech (Beijing) Biotechnology Co., Ltd.
First posted: 2025-01-13
Enrollment: 7
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicity
timeFrame: Within 28 days after infusion
measure: The incidence and frequency of treatment-emergent adverse events
timeFrame: Within 12 months after infusion
measure: Best overall response rate (BOR) of each dose group
timeFrame: Within 12 weeks after infusion
measure: Objective response rate (ORR) of each dose group
timeFrame: Within 4 weeks after infusion
measure: Time to response (TTR)
timeFrame: Within 6 months after infusion
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: