Aplastic Anemia
Conditions
Keywords
allo-HSCT, CD7 CAR-T
Brief summary
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
Detailed 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).
Interventions
CD7 CAR T cells treat patients with severe aplastic anemia
OTHERAllogeneic hematopoietic stem cell transplantation
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
Sponsors
Yake Biotechnology Ltd.
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
Primary ContactHe Z Huang, MD
Backup ContactYongxian Hu, MD
Outcome results
None listed