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

Status: Recruiting
Location: See location...
Intervention Type: Drug, Radiation
Study Type: Interventional
Study Phase: Phase 1
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

Eligibility
Participation Requirements
Sex: All
Maximum Age: 21
Healthy Volunteers: f
View:

∙ \*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

⁃ 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

⁃ 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

Locations
United States
Tennessee
St. Jude Children's Research Hospital
RECRUITING
Memphis
Contact Information
Primary
Rebecca Epperly, MD
referralinfo@stjude.org
8662785833
Time Frame
Start Date: 2025-12-05
Estimated Completion Date: 2031-11-05
Participants
Target number of participants: 42
Treatments
Experimental: RAD3CAR Treatment
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.
Sponsors
Leads: St. Jude Children's Research Hospital

This content was sourced from clinicaltrials.gov

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