Clinical trial NCT06769191: Clinical Study on the Safety and Efficacy of CD7 CAR-T Cell Sequential Allo-HSCT and Kidney Transplantation in the Treatment of SIOD
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Schimke Immuno-osseous Dysplasia
Keywords: CAR-T
Allo-HSCT
Kidney Transplantation
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2025-01-10
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after Treatment
measure: Transplant related mortality rate
timeFrame: Up to 100 days after Treatment
Secondary outcomes:
measure: Allogeneic hematopoietic stem cell transplant implantation rate
timeFrame: Up to 100 days after Treatment
measure: Kidney transplantation 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: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: He Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: