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. 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
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.
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 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%. 4. Bone Marrow Function Requirements: 1. Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; 2. Platelet count ≥ 30 × 10⁹/L; 3. International normalized ratio (INR) ≤ 1.5 × ULN; 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| • Dose Limiting Toxicity [Time Frame: Within 28 days after infusion] | Within 28 days | Safety assessments are conducted using the NCI-CTCAE version 5.0 standards. |
| • The incidence and frequency of treatment-emergent adverse events [Time Frame: Within 6 months after infusion] | Within 6 months | Safety assessments are conducted using the NCI-CTCAE version 5.0 standards. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| • Time to response (TTR) [Time Frame: Within 6 months after infusion] | Within 6 months | TTR is defined as the duration from cell infusion to the achievement of a hematological response |
| • Peak Plasma Concentration (Cmax) of YTS109 To evaluate the metabolic characteristics of YTS109 | Within 12 months after infusion | — |
| • Best overall response rate (BOR) of each dose group [Time Frame: Within 12 weeks after infusion] | Within 12 weeks | BOR is determined as the most favorable response observed after cell infusion, until either disease relapse or the completion of a specified observation |
| • Area under the plasma concentration versus time curve (AUC) of YTS109 To evaluate the metabolic characteristics of YTS109 | Within 12 months after infusion. | — |
| • The reconstitution of B cell in peripheral blood Changes in B cells quantification and phenotypic in peripheral blood | Within 12 months after infusion. | — |
| • Time to Peak (Tmax) of YTS109 To evaluate the metabolic characteristics of YTS109 | Within 12 months after infusion. | — |
| • Objective response rate (ORR) of each dose group [Time Frame: Within 4 weeks after infusion] | Within 4 weeks | — |
Contacts
Primary ContactHeng Mei Professor Heng Mei
Outcome results
None listed