CD7 CAR-T Cell Sequential Allo-HSCT for Non-malignant Blood and Immune System Diseases

Clinical Study on the Safety and Efficacy of CD7 CAR-T Cell Sequential Allogeneic Hematopoietic Stem Cell Transplantation for Non-malignant Blood and Immune System Diseases

A Clinical Study on the Safety and Effectiveness of CD7 CAR-T Cell Sequential Allogeneic Hematopoietic Stem Cell Transplantation for Non-malignant Blood and Immune System Diseases

Study Overview

• Status: Recruiting
• Conditions: Bone Marrow Failure Syndrome
• Intervention / Treatment: Procedure: Allo-HSCT; Biological: CD7 CAR-T cells injection

Detailed Description

This is a single-arm, open-label clinical trial to evaluate the safety and efficacy of CD7 CAR-T Cell Sequential Allogeneic Hematopoietic Stem Cell Transplantation for Non-malignant Blood and Immune System Diseases. It is planned to enroll 12-20 participants in this trial.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: He Huang, MD; Phone Number: 0571-87233772; Email: hehuangyu@126.com
• Study Contact Backup: Name: Yongxian Hu, MD; Phone Number: 0571-87233772; Email: huyongxian2000@aliyun.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university
      • 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:

• 1. Non-malignant blood and immune system diseases include: hereditary bone marrow failure, congenital immune deficiency, hemoglobinopathy and other non-malignant blood and immune system diseases,

  1. Confirmed hereditary bone marrow failure syndrome. Including: Fanconi anemia, congenital pure red cell aplastic anemia, congenital dyskeratosis, Scheux-Day syndrome, congenital neutropenia, various bone marrow failure related congenital thrombocytopenia and other unclassified congenital bone marrow exhaustion diseases;
  2. It meets the criteria of clinical manifestation, immune function and gene diagnosis of immune deficiency disease;
  3. Diagnosed with hemoglobinopathy and dependent on blood transfusions; serum ferritin levels are < 3000 μg/L, with cardiac and hepatic iron content indicating moderate or lower iron overload; documentation of iron chelation therapy (including prescriptions or invoices) for at least three months prior to screening is available; no hydroxyurea, ruxolitinib, decitabine, or cytarabine has been administered in the three months preceding enrollment. The spleen size must not extend beyond the umbilical horizontal line or the midline of the abdomen. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated, and suitable donors for related allo-HSCT are available.
• 2. Serum total bilirubin ≤1.5 times the upper limit of normal value, serum Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal value range;
• 3. Echocardiography showed Left ventricular ejection fraction (LVEF) >50%;
• 4. Pulse oxygen saturation ≥92% (non-oxygen state);
• 5. The estimated survival is more than 3 months;
• 6. ECOG score 0-1;
• 7. Abdominal B-ultrasonography and other examinations were performed to evaluate spleen size. Splenectomy should be evaluated before transplantation for patients with giant spleen;
• 8. Women and men who are fertile must consent to the use of appropriate contraception before entering the study, during study participation, and for 6 months after transfusion (the safety of this therapy for the unborn child is not known, with unknown risks);
• 9. Subjects who are willing to participate in the study are able to understand and have the ability to sign informed consent.

Exclusion Criteria:

• 1. People with a history of epilepsy or other central nervous system disorders;
• 2. Epstein-Barr virus (EBV) DNA positive;
• 3. People with a history of prolonged QT interval or serious heart disease;
• 4. People with active hepatitis B or C virus;
• 5. Tuberculosis, AIDS and other major infectious diseases;
• 6. Sepsis, pulmonary infection, intestinal infection and other major organ infection and poor control, and/or hypersensitive C-reactive protein, procalcitonin significantly elevated;
• 7. People who have previously received other clinical studies and gene therapy;
• 8. Any situation that the investigator believes may increase the risk to the subject or interfere with the test results.

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: CD7 CAR-T cells（ CD7 chimeric antigen receptor T cells）; Patients or donors undergo leukapheresis. Patients will receive a lymphodepletion chemotherapy with CTX、Flu、VP-16 before CAR-T cells infusion. CAR-T cells could be transfused after 48 hours of preconditioning.	Procedure: Allo-HSCT; allogeneic hematopoietic stem cell transplantation; Biological: CD7 CAR-T cells injection; Each subject receive CD7 CAR T-cells by intravenous infusion

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	Up to 2 years after Treatment
Transplant related mortality rate	The proportion of patients who died after transplantation to the total number of transplant patients during the same period	Up to 100 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: Yake Biotechnology Ltd.
• Investigators: Principal Investigator: He Huang, MD, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): January 31, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: January 16, 2025
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: CAR-T; Allo-HSCT; Immuno Deficiency Disorders
• Additional Relevant MeSH Terms: Cytopenia; Hematologic Diseases; Bone Marrow Diseases; Bone Marrow Failure Disorders; Immune System Diseases; Pancytopenia
• Other Study ID Numbers: TXB2024023

Drug and device information, study documents

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