CD7 CAR-T Bridging to alloHSCT for Severe Aplastic Anemia

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).

• CD7 CAR-T cells injection (Drug): CD7 CAR T cells treat patients with severe aplastic anemia
• Allogeneic hematopoietic stem cell transplantation (Other): In this study, Allogeneic hematopoietic stem cell transplantation is used as a bridge therapy to CD7 CAR T cells infusion to treat patients with severe aplastic anemia

Primary outcomes

• Dose-limiting toxicity (DLT) [Up to 28 days after Treatment]: Adverse events assessed according to NCI-CTCAE v5.0 criteria
• Incidence of treatment-emergent adverse events (TEAEs) [Up to 2 years after Treatment]: Incidence of treatment-emergent adverse events \[Safety and Tolerability\]

Secondary outcomes

• Allogeneic hematopoietic stem cell transplant implantation rate [Up to 100 days after Treatment]: The proportion of the number of patients who achieved hematopoietic reconstitution to the total number of allogeneic hematopoietic stem cell transplantation patients in the same period.
• Time to neutrophil and platelet engraftment [Up to 30 days after Treatment]: The time for neutrophils and platelets to reach the implantation criteria after stem cell reinfusion
• Disease-feesurvival，DFS [Up to 2 years after Treatment]: The proportion of disease-free patients who survived to the total number of patients who transplanted allogeneic hematopoietic stem cells during the same period.
• Overall survival, OS [Up to 2 years after Treatment]: After transplantation until death from any cause.

Sex: All

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.

• He Huang, MD, Principal investigator, Zhejiang University