Hypofractionated Radiation in Combination With B7-H3-CAR T Cells for Pediatric Patients With Relapsed/Refractory Sarcomas

NCT07222735 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: RAD3CARNCI-2025-07135
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

RAD3CAR is a phase I study designed to evaluatethe safety of B7-H3-CAR T cells and lymphodepletion in combination with hypofractionated radiation therapy. Primary objective: \- To evaluate the safety of B7-H3-CAR T cell therapy after priming with hypofractionated radiation therapy (HFRT) and lymphodepleting chemotherapy in patients ≤ 21 years of age with relapsed/refractory B7-H3+ sarcomas. Secondary objectives:

• To describe the antitumor activity of B7-H3-CAR T cells in combination with HFRT
• To determine if B7-H3-CAR T cells traffic to tumor sites after combination treatment with HFRT

Conditions

Sarcoma; Childhood Osteosarcoma; Ewing Sarcoma; Childhood Rhabdomyosarcoma; Childhood Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT) rate

  Proportion of evaluable participants experiencing DLTs

  up to 4 weeks after CAR T cell infusion

• Incidence of adverse events (AEs)

  AEs will be assessed and graded using CTCAE v5.0, except for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), which will be graded according to ASTCT consensus guidelines. AEs will be summarized and reported descriptively

  up to 4 weeks after CAR T cell infusion

Secondary Outcomes (2)

• Clinical antitumor activity

  4-12 weeks after CAR T cell infusion

• B7-H3-CAR T cell trafficking to tumor sites

  2 weeks after CAR T cell infusion

Study Arms (1)

RAD3CAR Treatment

EXPERIMENTAL

Peripheral blood mononuclear cells (PBMC) will be collected by autologous apheresis. Treatment will include HFRT to at least one site of disease, administered in parallel with a single course of lymphodepleting chemotherapy (fludarabine/cyclophosphamide) and followed by CAR T cell infusion.

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: B7-H3-CAR T Cells; Radiation: Radiation Therapy

Interventions

Fludarabine DRUG

Intravenously on day -5, -4, -3 and -2

RAD3CAR Treatment

Cyclophosphamide DRUG

Intravenously on day -3, -2

RAD3CAR Treatment

B7-H3-CAR T Cells DRUG

Intravenously on day 0

RAD3CAR Treatment

Radiation Therapy RADIATION

5 or 8 treatment sessions (fractions), scheduled to complete on Day -2

RAD3CAR Treatment

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \*a previously collected, autologous leukapheresis product can be used for T cell production
• Collection and manufacturing eligibility
• Age ≤ 21 years old
• B7-H3+ sarcoma; B7-H3 expression will be evaluated by standard immunohistochemistry (IHC) using any previously obtained biopsy; a tumor is considered B7-H3 positive with a H score greater than or equal to 100
• Osteosarcoma
• Ewing Sarcoma
• Rhabdomyosarcoma Non-rhabdomyosarcoma soft tissue sarcomas
• Evidence of relapsed (cancer that has completely responded \[i.e., no evidence of disease using standard imaging modalities\] to first-line therapy but has recurred for the first or subsequent time); or refractory (cancer that does not respond completely to treatment; cancer may be resistant at the beginning or may become resistant during treatment) disease after standard first-line therapy
• Evaluable disease with presence of at least one lesion amenable to hypofractionated radiation therapy
• For dose expansion cohort: participants must also have additional evaluable disease beyond planned radiation field
• Estimated life expectancy of \> 12 weeks
• Karnofsky or Lansky (age-dependent) performance score ≥ 60
• Participants with mobility limitations due to prior surgical intervention (i.e., amputation) but who are up in wheelchair or with other assistive devices will be considered ambulatory for the purpose of performance score determination
• For females of child-bearing age:
• Not pregnant with negative serum pregnancy test within 7 days prior to enrollment

You may not qualify if:

• Collection and manufacturing eligibility
• Known primary immunodeficiency
• Known HIV positivity
• Severe, uncontrolled intercurrent bacterial, viral, or fungal infection
• Known active malignancy other than the B7-H3+ sarcoma being treated on study
• Rapidly progressive disease (as assessed by the study PIs, with consideration for proximity to critical structures)
• Presence of intracranial or spinal cord disease
• Known underlying medical condition(s) for which, in the investigator's opinion, participation in this trial would not be in the best interest of the participant (e.g., compromises the health of the subject) or that could prevent, limit, or confound protocol assessments
• Known severe hypersensitivity to corn starch or hydroxyethyl starch
• Treatment eligibility
• Known primary immunodeficiency
• Known HIV positivity
• Severe, uncontrolled intercurrent bacterial, viral, or fungal infection
• Known active malignancy other than the B7-H3+ sarcoma being treated on study
• Receiving systemic steroid therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone, \< 7 days prior to CAR T cell infusion

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Related Links

• St. Jude Children's Research Hospital

MeSH Terms

Conditions

Sarcoma; Sarcoma, Ewing

Interventions

fludarabine; Cyclophosphamide; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Therapeutics

Study Officials

• Rebecca Epperly, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca Epperly, MD

CONTACT

8662785833; referralinfo@stjude.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: October 28, 2025
• First Posted: October 30, 2025
• Study Start: January 21, 2026
• Primary Completion (Estimated): November 5, 2030
• Study Completion (Estimated): November 5, 2031
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

US (1)