Autoimmune Hemolytic Anemia
Conditions
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 STAR-T cell therapy in patients with autoimmune hemolytic anemia who have failed ≥3 lines of therapy. This study set up two dosage groups: 1e6 STAR+T cells/kg and 2e6 STAR+T cells/kg. With the starting dose of 1e6 STAR+T cells/kg, it was conducted according to the traditional 3+3 design rule. In this study, if the safety was good but the efficacy was not satisfactory at the dosage level of 2e6 STAR+T cells/kg, SRC could decide whether to continue increasing the dose to 3e6 STAR+T cells/kg based on the clinical preclinical data, cumulative safety, tolerance, preliminary efficacy, PK and other results. If the subject shows no response (NR) or experiences recurrence after remission, a second infusion may be administered-provided the patient voluntarily consents and the investigator, after comprehensive assessment, determines that the potential benefits outweigh the risks. The investigator may decide on the timing of re-infusion, the use of lymphodepleting pretreatment, and the dose and number of re-infusions based on prior safety, efficacy, and pharmacokinetic (PK) data.
Interventions
DRUGYTS109 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.
Sponsors
China Immunotech (Beijing) Biotechnology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 18 ≤ Age ≤ 60 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: 1. 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). 2. Renal Function: Creatinine clearance (CrCl) ≥ 60 ml/minute (calculated using the Cockcroft-Gault formula). 3. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity | Within 28 days after infusion | — |
| The incidence and frequency of treatment-emergent adverse events | Within 6 months after infusion | Safety assessments are conducted using the NCI-CTCAE version 5.0 standards |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Peak Plasma Concentration (Cmax) of YTS109 | Within 12 months after infusion | To evaluate the metabolic characteristics of YTS109 |
| Time to Peak (Tmax) of YTS109 | Within 12 months after infusion | To evaluate the metabolic characteristics of YTS109 |
| Area under the plasma concentration versus time curve (AUC) of YTS109 | Within 12 months after infusion | To evaluate the metabolic characteristics of YTS109 |
| The reconstitution of B cell in peripheral blood | Within 12 months after infusion | Changes in B cells quantification and phenotypic in peripheral blood |
Countries
China
Contacts
CONTACTLiping Jing
Outcome results
None listed