SarcomaPhase 1NCT07222735
Hypofractionated Radiation in Combination With B7-H3-CAR T Cells for Pediatric Patients With Relapsed/Refractory Sarcomas
A Phase 1 study testing Fludarabine, Cyclophosphamide and B7-H3-CAR T Cells in people with Sarcoma and Childhood Osteosarcoma, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Sarcoma, Childhood Osteosarcoma, Childhood Rhabdomyosarcoma
- What is being tested?
- Fludarabine, Cyclophosphamide and B7-H3-CAR T Cells
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jan 2026to 5 Nov 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
- Not lactating with intent to breastfeed
- Participants must be eligible to undergo autologous apheresis or have an available previously collected autologous apheresis product
- Treatment eligibility
- Age ≤ 21 years old at the time of manufacturing
- B7-H3+ sarcoma
- Evidence of relapsed or refractory disease after standard first-line therapy
- Evaluable disease with the presence of at least one lesion amenable to hypofractionated radiation therapy
- For dose expansion cohort: participants must also have additional evaluable disease beyond the planned radiation field
- Estimated life expectancy of > 8 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 device will be considered ambulatory for purpose of performance score determination.
- Adequate cardiac function defined by echocardiogram with left ventricular ejection fraction ≥ 50%
- Adequate renal function as defined by not exceeding the maximum serum creatinine listed below by age:
- 1 to <2 years: 0.6
- 2 to <6 years: 0.8
- 6 to <10 years: 1
- 10 to <13 years: 1.2
- 13 to <16 years: male 1.5, female 1.4
- ≥ 16 years: male 1.7, female 1.4
- Adequate pulmonary function defined as pulse oximetry ≥ 92% on room air
- Total Bilirubin ≤3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age
- Hemoglobin ≥ 7g/dL (can be transfused)
- Platelet count ≥ 50,000/μL (can be transfused)
- Absolute neutrophil count (ANC) ≥ 1000/μL
- Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy
- For females of child-bearing age:
- Not pregnant with negative serum pregnancy test within 7 days prior to enrollment
- Not lactating with intent to breastfeed
- If sexually active, agreement to use contraception until 3 months after T cell infusion
Who cannot join
- 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)
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- 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
- Receiving systemic therapy < 14 days prior to start of protocol therapy, which will interfere with the activity of the CAR product (in the opinion of the study PIs)
- Received radiation therapy within the 4 weeks prior to start of protocol therapy
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Rebecca Epperly, MD, 866-278-5833, referralinfo@stjude.org
Rebecca Epperly, MD
About this study
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
Read the detailed description
This study is a phase I study designed to describe the safety of B7-H3-CAR T cells and lymphodepletion in combination with hypofractionated radiation therapy for the treatment of pediatric patients with B7-H3+ sarcoma.
The study will contain two-part eligibility criterion: one to proceed with autologous apheresis and manufacturing of CAR T cells, and a second to proceed with CAR T cell treatment.
The primary intervention is the administration of autologous B7-H3-CAR T cells, after priming with HFRT and administration of lymphodepleting chemotherapy. 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. Participants are evaluated for a post-treatment tumor biopsy and may choose to be evaluated for a pre-treatment tumor biopsy. Participants who meet specified criteria will be eligible for optional additional treatment courses.
- Conditions
- Sarcoma, Childhood Osteosarcoma, Childhood Rhabdomyosarcoma, Childhood Soft Tissue Sarcoma, Ewing Sarcoma
- Being tested
- Fludarabine, Cyclophosphamide, B7-H3-CAR T Cells, Radiation Therapy
- Medical subject headings
- Sarcoma, Sarcoma, Ewing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Intravenously on day -5, -4, -3 and -2
CyclophosphamideDrug
Intravenously on day -3, -2
B7-H3-CAR T CellsDrug
Intravenously on day 0
Radiation TherapyRadiation
5 or 8 treatment sessions (fractions), scheduled to complete on Day -2
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: B7-H3-CAR T Cells; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLT) rate
Proportion of evaluable participants experiencing DLTs
Measured: 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
Measured: up to 4 weeks after CAR T cell infusion
Secondary outcomes (2)
Clinical antitumor activity
Best overall response after treatment as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and if applicable bone marrow evaluation
Measured: 4-12 weeks after CAR T cell infusion
B7-H3-CAR T cell trafficking to tumor sites
Evaluate for the presence of B7-H3-CAR T cells in post-treatment tumor biopsies
Measured: 2 weeks after CAR T cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2025
- Study start21 Jan 2026
- Primary completion5 Nov 2030 (estimated)
- Study completion5 Nov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SarcomaStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rebecca Epperly, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07222735
- Sponsor's protocol ID
- RAD3CAR
- Other IDs
- NCI-2025-07135
- Status last verified
- Feb 2026
- First submitted
- 28 Oct 2025
- Last updated
- 9 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypofractionated Radiation in Combination With B7-H3-CAR T Cells for Pediatric Patients With Relapsed/Refractory Sarcomas
- ClinicalTrials.gov ID
- NCT07222735
- Acronym / sponsor ID
- RAD3CAR
- Conditions
- Sarcoma, Childhood Osteosarcoma, Childhood Rhabdomyosarcoma, Childhood Soft Tissue Sarcoma, Ewing Sarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- 21 Jan 2026 (actual)
- Primary completion
- 5 Nov 2030 (estimated)
- Study completion
- 5 Nov 2031 (estimated)
- First posted
- 30 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
This study is a phase I study designed to describe the safety of B7-H3-CAR T cells and lymphodepletion in combination with hypofractionated radiation therapy for the treatment of pediatric patients with B7-H3+ sarcoma.
The study will contain two-part eligibility criterion: one to proceed with autologous apheresis and manufacturing of CAR T cells, and a second to proceed with CAR T cell treatment.
The primary intervention is the administration of autologous B7-H3-CAR T cells, after priming with HFRT and administration of lymphodepleting chemotherapy. 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. Participants are evaluated for a post-treatment tumor biopsy and may choose to be evaluated for a pre-treatment tumor biopsy. Participants who meet specified criteria will be eligible for optional additional treatment courses.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD3CAR Treatment | Experimental | Drug: Fludarabine, Drug: Cyclophosphamide, Drug: B7-H3-CAR T Cells, Radiation: Radiation TherapyPeripheral 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. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (45 listed)
- 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
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FludarabineIntravenously on day -5, -4, -3 and -2 | Drug | RAD3CAR Treatment |
| CyclophosphamideIntravenously on day -3, -2 | Drug | RAD3CAR Treatment |
| B7-H3-CAR T CellsIntravenously on day 0 | Drug | RAD3CAR Treatment |
| Radiation Therapy5 or 8 treatment sessions (fractions), scheduled to complete on Day -2 | Radiation | RAD3CAR Treatment |
Primary outcome
Dose limiting toxicity (DLT) rate
Time frame: up to 4 weeks after CAR T cell infusion
Proportion of evaluable participants experiencing DLTs
Incidence of adverse events (AEs)
Time frame: up to 4 weeks after CAR T cell infusion
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
2 secondary outcomes
Clinical antitumor activity
Time frame: 4-12 weeks after CAR T cell infusion
B7-H3-CAR T cell trafficking to tumor sites
Time frame: 2 weeks after CAR T cell infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2026.
- St. Jude Children's Research HospitalLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rebecca Epperly, MD principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fludarabine, Cyclophosphamide and B7-H3-CAR T Cells in people with Sarcoma and Childhood Osteosarcoma, run by St. Jude Children's Research Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 45 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rebecca Epperly, MD (8662785833, referralinfo@stjude.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicity (DLT) rate (time frame: up to 4 weeks after CAR T cell infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2026.