Overview
This is a single-arm, open-label, single-center, phase I study. The primary objective is to evaluate the safety of CD7 CAR-T Bridging to allo-HSCT therapy for patients with severe aplastic anemia
Description
This is a prospective, open-label, single-center clinical trial. This study will evaluate the safety and efficacy of CD7 CAR-T Bridging to allo-HSCT in the treatment of severe aplastic anemia.The primary endpoints are dose limiting toxicity (DLT) and the incidence of treatment emergent adverse event (TEAE).
Eligibility
Inclusion Criteria:
- Chinese expert consensus on the diagnosis and treatment of aplastic anemia（2017）, Diagnosis of severe aplastic anemia ，1. The degree of bone marrow cell proliferation < 25%, or 25%-50% but residual hematopoietic cells < 30%；2. With pancytopenia (at least two of the following peripheral blood parameters) : (1) absolute neutrophil <0.5×10^9/L; (2) Platelet count< 20×10^9/L; (3) The absolute value of reticulocytes <20×109/L;
- Suitable donors (relatives) with allogeneic HSCT indications and at least haploid allogeneic transplantation;
- Patients who are not suitable or unwilling to undergo traditional allogeneic hematopoietic stem cell transplantation;
- creatinine clearance > 60ml/min; without liver invasion, serum total bilirubin ≤ 1.5 times the upper limit of normal, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were both ≤ 3 times the upper limit of the normal range. If there is liver invasion, serum erythrambirubin ≤ 3 times the upper limit of normal, and serum ALT and AST are both ≤ 5 times the upper limit of the normal range;
- Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
- No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
- Estimated survival time ≥ 3 months;
- ECOG performance status 0 to 1;
- Females and males of childbearing potential must agree to use adequate contraception prior to study entry, during study participation, and for 6 months after infusion (the safety of this therapy for unborn children is not known and has unknown risks);
- Those who voluntarily participated in this trial and provided informed consent;
Exclusion Criteria:
- Allergy to pre-treatment measures；
- Those with acute graft versus host disease (GvHD) or moderate to severe chronic GvHD within 4 weeks before screening; Those who have received systemic drug therapy for GvHD within 4 weeks before the reinfusion；
- History of epilepsy or other central nervous system disorders；
- Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
- Less than 100 days after allogeneic hematopoietic stem cell transplantation；
- Patients with HIV infection，Active infection of hepatitis B virus or hepatitis C virus，Uncured active infection；
- The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
- Received anti-cancer chemotherapy or other drug treatment within 2 weeks prior to screening;
- Any condition that, in the opinion of the investigator, may increase the risk to the subject or interfere with the results of the study.