cnct19 for patients with autoimmune hemolytic anemia after failure ≥3 lines of therapy.

Conditions: Autoimmune Hemolytic Anemia; Autologous CD19 CAR-T; Failure of Three or More Lines of Therapy

Summary: this is a phase 1, single-arm, open-label, dose-escalation and dose-expansion study. the main purpose is to evaluate the safety and tolerability, efficacy of cnct19 car t-cell therapy in patients with autoimmune hemolytic anemia after failure of three or more lines of therapy. participants will receive cnct19 cell infusion after preconditioning, and they will receive a 1-year follow-up.


Eligibility criteria:
inclusion criteria: * subject and/or subject's legal personal representative fully understand and voluntarily sign informed consent forms * male or female age ≥ 12 years * subjects with autoimmune hemolytic anemia or evans syndrome after failure ≥3 lines of therapy. the failure of ≥3 lines of therapy meets all the following conditions: hemoglobin less than 10g/dl and symptoms of anemia; failure of first-line corticosteroid therapy; failure of second-line rituximab therapy; failure of any one or more of the third-line treatments (splenectomy, cyclosporine, cyclophosphamide, azathioprine, mycophenolate mofetil, fludarabine, bortezomib, etc.) * female subjects of childbearing potential must have a negative serum hcg test within 7 days before enrollment. subjects of childbearing potential will be required to follow contraception requirements from the time of enrollment until the 1-year follow-up after cell infusion * laboratory tests of adequate organ function: serum alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤3×uln; and have a minimum level of pulmonary reserve defined as ≤ grade 1 dyspnea and the blood oxygen saturation in a non-oxygenated state is \>93% * ecog performance status ≤2 * subject with a life expectancy of more than 3 months exclusion criteria: * history of other lymphoproliferative neoplasms * secondary aiha caused by drugs or infection * platelets in subjects with evans syndrome\<30×10\^9/l * pregnant or breast-feeding subjects * treatment with any of the following within the noted period prior to study entry: 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 * 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 * had other inherited or acquired hemolytic diseases * 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 * received major surgery within 4 weeks before screening that was assessed by the researcher as 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 (except atrial fibrillation, paroxysmal supraventricular tachycardia), d.qtcb interval ≥450ms for men and ≥470ms for women, e.have myocardial infarction, bypass surgery, or stent placement within the 6 months before the study, f.other heart diseases judged by the researcher to be unsuitable for enrollment * have a history of live attenuated vaccines within 6 weeks before enrollment * participate in other interventional clinical studies during cnct19 car t-cell therapy, and the drug has a half-life of \<5. subjects treated with active investigational drugs or intend to participate in another clinical trial or receive treatment other than that specified in the protocol throughout the study period * 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: autoimmune hemolytic anemia cnct19 car t-cell therapy