Schimke Immuno-osseous Dysplasia
Conditions
Keywords
CAR-T, Allo-HSCT, Kidney Transplantation
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.
Interventions
BIOLOGICALCD7 CAR-T cells injection
Intravenous infusion, single dose
PROCEDUREAllo-HSCT
allogeneic hematopoietic stem cell transplantation
PROCEDUREKidney Transplantation
Kidney Transplantation
Sponsors
Yake Biotechnology Ltd.
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) | Up to 2 years after Treatment | Incidence of treatment-emergent adverse events |
| Transplant related mortality rate | Up to 100 days after Treatment | The proportion of patients who died after transplantation to the total number of transplant patients during the same period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to neutrophil and platelet engraftment | Up to 30 days after Treatment | The time for neutrophils and platelets to reach the implantation criteria after stem cell reinfusion |
| Allogeneic hematopoietic stem cell transplant implantation rate | Up to 100 days after Treatment | 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. |
| Overall survival, OS | Up to 2 years after Treatment | After transplantation until death from any cause. |
| Disease-feesurvival，DFS | Up to 2 years after Treatment | The proportion of disease-free patients who survived to the total number of patients who transplanted allogeneic hematopoietic stem cells during the same period. |
| Kidney transplantation implantation rate | Up to 100 days after Treatment | The ratio of successfully implanted kidneys to the total implanted kidneys |
Countries
China
Contacts
Primary ContactHe Huang, MD
Backup ContactYongxian Hu, MD
Outcome results
None listed