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 5E6 cells/kg or the starting dose may be adjusted based on accumulated data.
Interventions
DRUGYTS109 cell
Subjects will receive YTS109 cell, and dose escalation will commence at 5E6 cells/kg or the starting dose may be adjusted based on accumulated data.
Sponsors
China Immunotech (Beijing) Biotechnology Co., Ltd.
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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.
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 12 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
STUDY_CHAIRJun Shi
Institute of Hematology & Blood Diseases Hospital, China
Outcome results
None listed