Selective Antigen Specific T Cells and CAR T Cells in Subjects With Relapsed/Refractory Embryonal Tumors (SABRE)

NCT07172958 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00001593
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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 and combined in a 1:1 ratio. 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.

Conditions

Ewing Sarcoma; Neuroblastoma; Rhabdomyosarcoma; Wilms Tumor

Keywords

CAR T Therapy for Embryonal tumors; T cell Therapy for Embryonal tumors

Outcome Measures

Primary Outcomes (3)

• To determine the safety of autologous CAR-TA T cells following LD chemotherapy in participants with relapsed/refractory rhabdomyosarcoma, Ewing sarcoma, neuroblastoma and Wilms tumor.

  The safety endpoint will be assessed by monitoring for dose limiting toxicities (DLT) for 28 days following CAR-TA T cell investigational product administration.

  Within 28 days from the CAR-TA T cell infusion

• To determine the manufacturing feasibility of autologous CAR-TA T cells following LD chemotherapy in participants with relapsed/refractory rhabdomyosarcoma, Ewing sarcoma, neuroblastoma and Wilms tumor.

  Manufacturing feasibility will be determined by the number of CAR-TA T cell products produced in sufficient quantities to meet the participant's assigned dose level for at least one infusion, with all product release testing criteria met.

  Within 28 days from the CAR-TA T cell infusion

• To determine the clinical feasibility of autologous CAR-TA T cells following LD chemotherapy in participants with relapsed/refractory rhabdomyosarcoma, Ewing sarcoma, neuroblastoma and Wilms tumor.

  Clinical feasibility will be determined by the number of participants with a released product who are eligible and receive at least 1 infusion.

  Within 28 days from the CAR-TA T cell infusion

Secondary Outcomes (11)

• Determine number of patients who respond to CAR-TA T cell therapy for treatment of diseases under study

  Within 15 years of infusion of CAR-TA T cell therapy.

• Overall Survival

  Within 12 months of CAR-TA T cell infusion.

• To characterize the in vivo immune milieu pre- and post-infusion of CAR-TA T cell product.

  Within 15 years of infusion of CAR-TA T cell therapy.

• To characterize transgene transduction efficiency (B7-H3 CAR and dTBRII) of the CAR-TA T cell product generated prior to infusion.

  Within 15 years of infusion of CAR-TA T cell therapy.

• To characterize reconstitution of anti-tumor immunity following infusion.

  Within 15 years of infusion of CAR-TA T cell therapy.

Study Arms (1)

This is single arm study.

EXPERIMENTAL

Lymphodepleting chemotherapy regimen with cyclophosphamide and fludarabine will be administered prior to CAR-TA T cell product infusion. 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.

Biological: Selective Antigen Specific dTβRII-expressing T cells combined with B7-H3 CAR T cells

Interventions

Selective Antigen Specific dTβRII-expressing T cells combined with B7-H3 CAR T cells BIOLOGICAL

Selective Antigen Specific dTβRII-expressing T cells combined with B7-H3 CAR T cells

This is single arm study.

Eligibility Criteria

• Age: 1 Year - 23 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of relapsed/refractory rhabdomyosarcoma, Ewing sarcoma, neuroblastoma, or Wilms tumor
• Refractory disease, residual detectable disease or relapsed disease following available standard of care therapies with known clinical benefit for their specific tumor type, or unable to receive such therapies due to unacceptable toxicity or contraindication
• Measurable or evaluable disease by imaging, as determined following most recent therapy
• Age ≥ 1 year and \< 24 years
• Weight ≥ 10 kg
• No systemic steroid exposure within 1 week of procurement
• Karnofsky/Lansky score of ≥ 60 (See Appendix 3)
• Participants of childbearing potential or capable of fathering a child must agree to use effective contraceptive measure/s (as described in Appendix 5) during study protocol participation through 6 months following the administration of the CAR-TA T cells
• ANC \> 500/µL
• ALC \> 1000/µL
• Platelet count \> 50,000/uL (level can be achieved with transfusion)
• Bilirubin ≤ 2.5 mg/dL
• Aspartate aminotransferase (AST)/Alanine transaminase (ALT) ≤ 5x the upper limit of normal for age
• Serum creatinine Maximum serum creatinine (mg/dL) Age Male Female
• to \< 2 years 0.6 0.6

You may not qualify if:

• Patients with known CNS disease.
• Patients with uncontrolled infection/s or known HIV infection
• Pregnant or lactating females.
• Patients who have undergone previous allogeneic stem cell transplant.
• Inability to tolerate leukapheresis (including any contraindication to the use of Anticoagulant Citrate Dextrose solution).
• Patients with uncontrolled infections or known HIV infection.
• Pregnant or lactating females
• Whole lung/mediastinal radiation within 12 weeks
• Clinically significant systemic illness or medical condition likely to interfere with assessment of safety or efficacy
• Patients who have received any live vaccine in the six weeks prior to planned initiation of lymphodepletion
• Any contraindication to lymphodepletion or to the use of Cyclophosphamide or Fludarabine, as per the clinical judgment of the PI or treating Sub-I
• History of allergy or hypersensitivity to study product excipients (e.g., DMSO)

Sponsors & Collaborators

• Children's National Research Institute: lead
• National Cancer Institute (NCI): collaborator
• Cancer Research UK: collaborator

Study Sites (2)

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Childrens National Hospital

Washington D.C., District of Columbia, 20010, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Rhabdomyosarcoma; Sarcoma, Ewing; Neuroblastoma; Wilms Tumor

Condition Hierarchy (Ancestors)

Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Holly Meany, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

• Amy Hont, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Holly Meany, MD

CONTACT

2024765697; HMeany@childrensnational.org

Fahmida Hoq, MBBS

CONTACT

2024763634; FHoq@childrensnational.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Med Dir Solid Tumor Program

Study Record Dates

• First Submitted: September 8, 2025
• First Posted: September 15, 2025
• Study Start: January 27, 2026
• Primary Completion (Estimated): December 1, 2041
• Study Completion (Estimated): December 1, 2044
• Last Updated: August 13, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)