a study of yts109 cell injection in subjects with relapsed/refractory autoimmune hemolytic anemia

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

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.

Keywords: relapsed/refractory autoimmune hemolytic anemia cd19-star t cells