CD7 CAR-T Bridging to alloHSCT for Severe Aplastic Anemia

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

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

Study Overview

• Status: Recruiting
• Conditions: Aplastic Anemia
• Intervention / Treatment: Drug: CD7 CAR-T cells injection; Other: Allogeneic hematopoietic stem cell transplantation

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).

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yongxian Hu, MD; Phone Number: 86-15957162012; Email: huyongxian2000@aliyun.com
• Study Contact Backup: Name: He Z Huang, MD; Phone Number: 13605714822; Email: hehuangyu@126.com

Study Locations

• China
  • Zhejiang
    • Hanzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: He Huang, MD; Phone Number: 0571-87233772; Email: hehuangyu@126.com
      • Contact: Yongxian Hu, MD; Phone Number: 0571-87233772; Email: huyongxian2000@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; Aplastic Anemia	Drug: CD7 CAR-T cells injection; CD7 CAR T cells treat patients with severe aplastic anemia; Other: Allogeneic 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Shanghai YaKe Biotechnology Ltd.
• Investigators: Principal Investigator: He Huang, MD, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): October 20, 2024
• Primary Completion (Estimated): October 20, 2027
• Study Completion (Estimated): October 20, 2027

Study Registration Dates

• First Submitted: October 8, 2024
• First Submitted That Met QC Criteria: October 8, 2024
• First Posted (Estimated): October 9, 2024

Study Record Updates

• Last Update Posted (Estimated): October 9, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: allo-HSCT; CD7 CAR-T
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Anemia; Anemia, Aplastic
• Other Study ID Numbers: TXB2024009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No