Ignite Creation Date:
2025-12-25 @ 12:00 AM
Ignite Modification Date:
2025-12-25 @ 9:58 PM
Study NCT ID:
NCT07172958
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-09-23
First Post:
2025-09-08
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Selective Antigen Specific T Cells and CAR T Cells in Subjects With Relapsed/Refractory Embryonal Tumors (SABRE)
Sponsor:
Children's National Research Institute
Organization:
Study Overview
Official Title:
Selective Antigen Specific dTβRII-expressing T Cells and B7-H3 CAR T Cells in Subjects With Relapsed/Refractory Embryonal Tumors (SABRE)
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SABRE
Brief Summary:
This is a phase I dose-escalation study to determine the safety and feasibility of autologous CAR-TA T cells (B7-H3 CAR+ T cells administered with DNR-PRAME Tumor Antigen-specific T cells) following lymphodepleting chemotherapy in participants with relapsed/refractory rhabdomyosarcoma, Ewing sarcoma, neuroblastoma and Wilms tumor.
Patients will be enrolled to one of three planned dose levels with B7-H3 CAR T cell dose determined based on the percentage of B7-H3 transduced cells (B7-H3+ population of cells), and dTBRII-transduced PRAME TA-specific T cell dose based on the total cell population. Both doses will be based on the recipient's body weight.
The safety of the CAR-TA T cell product will be evaluated and the maximum tolerated dose (MTD) will be determined. The safety endpoint will be assessed by monitoring for dose limiting toxicities for 28 days following CAR-TA T cell administration.
Patients will be enrolled to one of three planned dose levels with B7-H3 CAR T cell dose determined based on the percentage of B7-H3 transduced cells (B7-H3+ population of cells), and dTBRII-transduced PRAME TA-specific T cell dose based on the total cell population. Both doses will be based on the recipient's body weight.
The safety of the CAR-TA T cell product will be evaluated and the maximum tolerated dose (MTD) will be determined. The safety endpoint will be assessed by monitoring for dose limiting toxicities for 28 days following CAR-TA T cell administration.
Detailed Description:
This protocol is designed as a phase I dose-escalation study. Procurement phase: During the procurement phase of this protocol, upon SABRE Procurement Consent and procurement eligibility confirmation, participants will undergo a non-mobilized apheresis for collection of mononuclear cells to be used for the CAR-TA T cell product manufacturing.
Treatment phase: Once the CAR-TA T cell products are released and patients are confirmed eligible for CAR-TA T cell product infusion, participants will undergo protocol therapy at Children's National Hospital, consisting of a standard Lymphodepleting chemotherapy preparative regimen with fludarabine and cyclophosphamide, followed by intravenous infusion of the combined CAR-TA T cell product. The DNR-TA T cells and B7-H3 CAR T cells will be generated and combined into a final product comprised of the two T cell components combined at a 1:1 ratio. Patients will be enrolled to one of three CAR-TA T cell product dose levels (dose levels 1, 2 and 3). There are provisions in place to dose de-escalate for safety concerns (dose level -1).
Fludarabine will be administered intravenously once daily over 30 minutes, days -5 through -2 (4 doses in total). The dose of fludarabine will be 30 mg/m2 /day. Cyclophosphamide will be administered intravenously once daily over 30 minutes, days -5 and -4 (2 doses in total). The dose of cyclophosphamide will be 500 mg/m2 /day.
The first 3 patients enrolled on study will be ≥ 12 years of age at enrollment and treated at dose level 1 (1 x 10e6/kg). If no DLTs are observed in this cohort, enrollment at dose levels 2 (3 x 10e6/kg) and 3 (10 x 10e6/kg) will expand to include patients aged ≥ 1 year and \< 24 years.
Patients will remain admitted for at least 7 days following the CAR-TA T cell infusion. All infused patients will be followed with weekly visits during the 28-day dose-limiting toxicity monitoring period where they will be clinically assessed, and safety and research blood draws will be performed.
Ideally, patients should not receive other systemic or local cancer-directed therapies for at least 28 days after the CAR-TA T cell infusion.
Participants will be followed closely for 1 year following the CAR-TA T-cell infusion. After 1 year, yearly assessments will be done up to 15 years. The visits will consist of labs and examinations as well as talking to participants about how they are feeling. Participants will be followed for toxicity until the last follow-up post CAR-TA T cell product administration.
This study will be conducted at Children's National Hospital (CNH). Cell culture manipulations will be carried out in the CETI Good Manufacturing Practice (GMP) facility within Children's National Hospital using current standard operating procedures (SOPs).
Up to 18 participants will be treated on this protocol to meet the primary objective over an estimated accrual period of 5 years
Treatment phase: Once the CAR-TA T cell products are released and patients are confirmed eligible for CAR-TA T cell product infusion, participants will undergo protocol therapy at Children's National Hospital, consisting of a standard Lymphodepleting chemotherapy preparative regimen with fludarabine and cyclophosphamide, followed by intravenous infusion of the combined CAR-TA T cell product. The DNR-TA T cells and B7-H3 CAR T cells will be generated and combined into a final product comprised of the two T cell components combined at a 1:1 ratio. Patients will be enrolled to one of three CAR-TA T cell product dose levels (dose levels 1, 2 and 3). There are provisions in place to dose de-escalate for safety concerns (dose level -1).
Fludarabine will be administered intravenously once daily over 30 minutes, days -5 through -2 (4 doses in total). The dose of fludarabine will be 30 mg/m2 /day. Cyclophosphamide will be administered intravenously once daily over 30 minutes, days -5 and -4 (2 doses in total). The dose of cyclophosphamide will be 500 mg/m2 /day.
The first 3 patients enrolled on study will be ≥ 12 years of age at enrollment and treated at dose level 1 (1 x 10e6/kg). If no DLTs are observed in this cohort, enrollment at dose levels 2 (3 x 10e6/kg) and 3 (10 x 10e6/kg) will expand to include patients aged ≥ 1 year and \< 24 years.
Patients will remain admitted for at least 7 days following the CAR-TA T cell infusion. All infused patients will be followed with weekly visits during the 28-day dose-limiting toxicity monitoring period where they will be clinically assessed, and safety and research blood draws will be performed.
Ideally, patients should not receive other systemic or local cancer-directed therapies for at least 28 days after the CAR-TA T cell infusion.
Participants will be followed closely for 1 year following the CAR-TA T-cell infusion. After 1 year, yearly assessments will be done up to 15 years. The visits will consist of labs and examinations as well as talking to participants about how they are feeling. Participants will be followed for toxicity until the last follow-up post CAR-TA T cell product administration.
This study will be conducted at Children's National Hospital (CNH). Cell culture manipulations will be carried out in the CETI Good Manufacturing Practice (GMP) facility within Children's National Hospital using current standard operating procedures (SOPs).
Up to 18 participants will be treated on this protocol to meet the primary objective over an estimated accrual period of 5 years
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: