B7-H3-CAR T Cells + Radiation for Childhood Cancer

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Systemic steroids

Disqualifiers: HIV, Active infection, Other malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for children and young adults under 21 with certain cancers that have returned or resisted standard treatment. It combines a special cell therapy called B7-H3-CAR T cells with radiation and chemotherapy to assess safety and effectiveness. The trial seeks participants with specific types of sarcomas, such as osteosarcoma or Ewing sarcoma, that have relapsed or are treatment-resistant. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic steroid therapy exceeding a certain dose 7 days before the CAR T cell infusion and any systemic therapy 14 days before starting the trial treatment. If you're on these medications, you may need to stop or adjust them.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that B7-H3-CAR T cells, a type of cell therapy for cancer, have been tested in early studies and appear well-tolerated. One study found that using these cells in children and young adults was manageable, with patients not experiencing severe side effects. Another study discovered that these CAR T cells did not mistakenly attack healthy cells.

These findings suggest the treatment is relatively safe, but it's important to remember that this trial is in its first phase. This phase focuses on assessing safety, so while results are promising, the full safety picture is still emerging. Participants in this trial will contribute to gathering more information about the treatment's safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about B7-H3-CAR T Cells because they offer a novel approach to treating childhood cancer by targeting the B7-H3 protein, which is often present on cancer cells but not on most normal cells. Unlike traditional chemotherapy, which can affect both cancerous and healthy cells, CAR T Cells are engineered to specifically seek out and destroy cancer cells, potentially leading to fewer side effects. Additionally, combining this targeted therapy with radiation and lymphodepleting chemotherapy could enhance its effectiveness, offering a new hope for better outcomes in young patients battling cancer.

What evidence suggests that B7-H3-CAR T cells combined with radiation might be an effective treatment for childhood cancer?

Research has shown that B7-H3-CAR T cells, which participants in this trial will receive, are highly active against solid tumors in children. These cells target a protein called B7-H3, found in many cancers, and have proven effective in early lab studies. Animal tests have demonstrated promising results for difficult childhood cancers, such as osteosarcoma. Another study supported their potential for various childhood cancers, indicating they can effectively attack cancer cells. Early human trials suggested that these treatments can be administered safely, even in challenging cases like brain tumors. ^{2 6 7 8 9}

Who Is on the Research Team?

Rebecca Epperly, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for pediatric patients aged 21 or younger with relapsed/refractory sarcomas that express B7-H3. Participants must have tried standard treatments without success and be able to handle the side effects of chemotherapy.

Inclusion Criteria

Estimated life expectancy of > 12 weeks

For sexually active females of child-bearing age: agreement to use contraception until 3 months after T cell infusion

I am 21 years old or younger.

Exclusion Criteria

Known primary immunodeficiency

Known underlying medical condition(s) that could compromise the health of the participant or confound protocol assessments

Known severe hypersensitivity to corn starch or hydroxyethyl starch

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and Manufacturing

Peripheral blood mononuclear cells (PBMC) are collected by autologous apheresis for CAR T cell manufacturing

2-3 weeks

Treatment

Participants receive hypofractionated radiation therapy (HFRT) and lymphodepleting chemotherapy followed by B7-H3-CAR T cell infusion

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and dose limiting toxicities

4-12 weeks

Optional Additional Treatment

Participants who meet specified criteria may be eligible for optional additional treatment courses

What Are the Treatments Tested in This Trial?

Interventions

• B7-H3-CAR T Cells
• Cyclophosphamide
• Fludarabine
• Hypofractionated Radiation Therapy

Trial Overview The RAD3CAR study tests the safety of a new therapy combining B7-H3-CAR T cells with hypofractionated radiation and lymphodepleting chemo (Fludarabine, Cyclophosphamide) in young patients with specific sarcomas.

How Is the Trial Designed?

Group I: RAD3CAR Treatment Experimental Treatment 4 Interventions

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.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2772610X24000199

CAR T cells redirected to B7-H3 for pediatric solid tumors CAR T cells targeting B7-H3, a pan-cancer antigen, demonstrate potent preclinical activity against pediatric solid tumors and brain tumors.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8456711/

CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen ... B7-H3 CAR T cells show significant in vivo activity against a range of xenograft models of lethal childhood cancers, including orthotopic models of osteosarcoma ...

3. scholarlyexchange.childrensmercy.org scholarlyexchange.childrensmercy.org/researchdays/GME_Research_Days_2024/ResearchDay3/2/

Therapeutic Efficacy of B7-H3 CAR T Cell Therapy In ... This study aims to assess the potential of anti-B7-H3 CAR T cell therapy in treating the challenging pHGG tumors.

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2019/car-t-cell-childhood-cancers

CAR T-Cell Study Suggests Promise for Childhood Cancers A CAR T-cell therapy targeting the B7-H3 protein may have potential as a treatment for several childhood cancers, results from a study in ...

5. nature.com nature.com/articles/s41591-024-03451-3

Intracerebroventricular B7-H3-targeting CAR T cells for ... This completed first-in-human trial shows that repetitive ICV dosing of B7-H3 CAR T cells in pediatric and young adult patients with DIPG is tolerable.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11218663/

CAR T cells redirected to B7-H3 for pediatric solid tumors Based on the encouraging preclinical data and safety profile, B7-H3 CAR T cells are now being evaluated in early phase clinical studies. Table 1 outlines “ ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1040842825000368

CAR T-cell therapy landscape in pediatric, adolescent and ... For instance, systemic administration of B7-H3 CAR-T cells has shown significant regression and eradication of osteosarcoma, Ewing sarcoma, and medulloblastoma ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06612645

Safety and Efficacy of CMD03 CAR T Cell in Children With ... A Phase 1 clinical trial to evaluate the safety and early efficacy of CAR T-cells with IL-7Ra signal targeting B7H3 in children with solid tumors patients after ...

9. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.23.02229

STRIvE-02: A First-in-Human Phase I Study of Systemically ... B7-H3 CAR T cells are tolerable and demonstrate limited antitumor activity without acute on-target, off-tumor toxicity. High levels of CAR T ...