Clinical trial NCT06633328: CD7 CAR-T Bridging to alloHSCT for Severe Aplastic Anemia
Official title: Clinical Study on the Safety and Efficacy of Donor Derived CD7 CAR-T Cell Bridging Allogeneic Hematopoietic Stem Cell Transplantation for the for Patients With Severe Aplastic Anemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Aplastic Anemia
Keywords: allo-HSCT
CD7 CAR-T
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2024-10-09
Enrollment: 30
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Up to 28 days after Treatment
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after Treatment
Secondary outcomes:
measure: Allogeneic hematopoietic stem cell transplant implantation rate
timeFrame: Up to 100 days after Treatment
measure: Time to neutrophil and platelet engraftment
timeFrame: Up to 30 days after Treatment
measure: Disease-feesurvival，DFS
timeFrame: Up to 2 years after Treatment
measure: Overall survival, OS
timeFrame: Up to 2 years after Treatment
Other outcomes:
Locations:
city: Hanzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: He Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: