Clinical Study on the Safety and Efficacy of CD7 CAR-T Cell Sequential Allo-HSCT and Kidney Transplantation in the Treatment of SIOD

Clinical Study on the Safety and Efficacy of CD7 CAR-T Cell Sequential Allogeneic Hematopoietic Stem Cell Transplantation and Kidney Transplantation in the Treatment of Schimke Immuno-osseous Dysplasia

A Clinical Study on the Safety and Effectiveness of CD7 CAR-T Cell Sequential Allo-HSCT and Kidney Transplantation in the treatment of Schimke immuno-osseous dysplasia

Study Overview

• Status: Recruiting
• Conditions: Schimke Immuno-osseous Dysplasia
• Intervention / Treatment: Biological: CD7 CAR-T cells injection; Procedure: Allo-HSCT; Procedure: Kidney Transplantation

Detailed Description

This is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety and efficacy of CD7 CAR-T Cell Sequential Allo-HSCT and Kidney Transplantation in patients with Schimke immuno-osseous dysplasia. It is planned to enroll 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: 057187233772; Email: hehuangyu@126.com
• Study Contact Backup: Name: Yongxian Hu, MD; Phone Number: 057187233772; 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. Diagnosed as SIOD and was in stage 5 of chronic kidney disease
• 2. Having allogeneic HSCT indications, at least suitable donors (relatives) for haploidentical allogeneic transplantation and kidneys from stem cell transplantation donors;
• 3. 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.
• 4. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
• 5. There is no active pulmonary infection, and the oxygen saturation during air inhalation is more than 92%；
• 6. Estimated survival time ≥ 3 months;
• 7. ECOG performance status 0 to 1;
• 8. Pregnant/lactating women, or male or female patients who have fertility and are willing to take effective contraceptive measures at least 6 months after the last cell infusion during the study period;
• 9. Those who voluntarily participated in this trial and provided informed consent;

Exclusion Criteria:

• 1. Allergic to pretreatment measures
• 2. received any containing ATG/ALG such IST、alemtuzumab、high-dose cyclophosphamide (≥ 45mg/kg/day) , received CsA treatment within 6 months, or used thrombopoietin receptor (tpo-r) agonists in the past;
• 3. Patients with the history of epilepsy or other CNS disease;
• 4. Patients with prolonged QT interval time or severe heart disease;
• 5. Previous recipients of allogeneic hematopoietic stem cell transplantation or organ transplantation
• 6. People infected with HIV, active hepatitis B or hepatitis C virus, and patients with active infection who are not cured;
• 7. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
• 8. Patients with malignant tumor;
• 9. People with other genetic diseases；
• 10. After receiving CD7 car-t treatment, patients who were unable to accept subsequent kidney transplantation due to severe infection or poor amplification of car-t in vivo.
• 11. Any situation that researchers believe may increase the risk to the subjects or interfere with the trial 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: Treatment Group; Schimke Immuno-osseous Dysplasia	Biological: CD7 CAR-T cells injection; Intravenous infusion, single dose; Procedure: Allo-HSCT; allogeneic hematopoietic stem cell transplantation; Procedure: Kidney Transplantation; Kidney Transplantation

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
Kidney transplantation implantation rate	The ratio of successfully implanted kidneys to the total implanted kidneys	Up to 100 days 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 30, 2025
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): January 30, 2028

Study Registration Dates

• First Submitted: January 2, 2025
• First Submitted That Met QC Criteria: January 8, 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; Kidney Transplantation; Allo-HSCT
• Additional Relevant MeSH Terms: Urogenital Diseases; Bone Diseases; Musculoskeletal Diseases; Vascular Diseases; Cardiovascular Diseases; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Immune System Diseases; Respiratory Tract Diseases; Odontogenic Tumors; Neoplasms by Histologic Type; Lung Diseases; Embolism and Thrombosis; Embolism; Arterial Occlusive Diseases; Bone Diseases, Developmental; Nephrosis; Pulmonary Embolism; Immunologic Deficiency Syndromes; Arteriosclerosis; Nephrotic Syndrome; Osteochondrodysplasias; Cementoma
• Other Study ID Numbers: TXB2024022

Drug and device information, study documents

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