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. 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; Wilms Tumor; Rhabdomyosarcoma

Keywords

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

Outcome Measures

Primary Outcomes (12)

• Grade 3 or more immediate infusion-related adverse event

  Number of patients experiencing Grade 3 or higher immediate infusion-related adverse events, assessed using the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0; Grades 1-5; higher grades indicate worse severity), occurring during or immediately following the CAR-TA T cell infusion.

  Within 28 days from the CAR-TA T cell infusion

• Grade 4 or more Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS)

  Number of patients experiencing Grade 4 or higher Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), assessed using the American Society for Transplantation and Cellular Therapy (ASTCT) CRS and ICANS Consensus Grading Criteria (Grades 1-5; higher grades indicate worse severity).

  Within 28 days from the CAR-TA T cell infusion

• Grade 3 neurotoxicity or ICANS persisting for more than 72 hours

  Number of patients experiencing Grade 3 neurotoxicity or ICANS with a duration greater than 72 hours. (severity grades assessed as per American Society for Transplantation and Cellular Therapy (ASTCT) CRS and ICANS Consensus Criteria)

  Within 28 days from the CAR-TA T cell infusion

• Grade 4 or more Cytokine Release Syndrome (CRS)

  Number of patients experiencing Grade 4 or higher Cytokine Release Syndrome (CRS), assessed using ASTCT CRS Consensus Grading Criteria (Grades 1-5; higher = worse).

  Within 28 days from the CAR-TA T cell infusion

• Grade 3 Cytokine Release Syndrome (CRS) lasting more than 14 days

  Number of patients experiencing Grade 3 CRS with a duration greater than 14 days

  Within 28 days from the CAR-TA T cell infusion

• Grade 3 or more Hemophagocytic Lymphohistiocytosis (HLH)

  Number of patients experiencing Grade 3 or higher Hemophagocytic Lymphohistiocytosis (HLH), assessed using CTCAE v5.0.

  Within 28 days from the CAR-TA T cell infusion

• Grade 3 or more fever lasting for more than 14 days

  Number of patients experiencing fever of Grade 3 or higher, persisting longer than 14 days, assessed using CTCAE v5.0.

  Within 28 days from the CAR-TA T cell infusion

• Grade 4 or more infection uncontrolled for more than 7 days

  Number of patients experiencing infection of Grade 4 or higher severity that is uncontrolled for more than 7 days, assessed using CTCAE v5.0.

  Within 28 days from the CAR-TA T cell infusion

• Any unexpected toxicity of Grade 2 or more

  Number of patients experiencing unexpected toxicities of Grade 2 or higher, assessed using CTCAE v5.0.

  Within 28 days from the CAR-TA T cell infusion

• Any expected toxicity above Grade 4

  Number of patients experiencing expected toxicity above Grade 4 (i.e., Grade 5 toxicity), assessed using CTCAE v5.0.

  Within 28 days from the CAR-TA T cell infusion

• Any expected toxicity above Grade 3 lasting longer than 72 hours

  Number of patients experiencing expected toxicity greater than Grade 3, persisting longer than 72 hours, assessed using CTCAE v5.0.

  Within 28 days from the CAR-TA T cell infusion

• Grade 2 toxicity persisting for more than 7 days AND considered intolerable to the patient and/or not controlled with standard supportive care

  Number of patients experiencing Grade 2 toxicity persisting for more than 7 days that is intolerable to the patient and/or not controlled with standard supportive care, assessed using CTCAE v5.0.

  Within 28 days from the CAR-TA T cell infusion

Secondary Outcomes (3)

• Response to CAR-TA T cell therapy

  Up to 5 years from the CAR-TA T cell infusion

• Progression-free survival

  Up to 12 months from the CAR-TA T cell infusion

• Overall survival

  Up to 12 months from the CAR-TA T cell infusion

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.
• 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

Sponsors & Collaborators

• Children's National Research Institute: lead
• National Cancer Institute (NCI): collaborator
• Cancer Research UK: collaborator
• The Mark Foundation for Cancer Research: 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: SPONSOR

Study Record Dates

• First Submitted: September 8, 2025
• First Posted: September 15, 2025
• Study Start: January 27, 2026
• Primary Completion (Estimated): December 1, 2035
• Study Completion (Estimated): December 1, 2038
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)