CAR T-Cell Therapy for Pediatric Cancer

Overseen By Chris DeRenzo, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Systemic steroids

Disqualifiers: Primary immunodeficiency, HIV, Severe infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new immunotherapy for children and young adults with certain stubborn cancers. The treatment uses special T cells, engineered to target and attack cancer cells, known as B7-H3 CAR T cells. Researchers aim to determine the safest dose of these modified T cells and assess their effectiveness against cancer. The trial seeks participants who are 21 years old or younger, have a type of solid tumor that has returned or hasn't responded to other treatments, and have a positive B7-H3 marker on their cancer cells. As a Phase 1 trial, this research focuses on understanding 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 infusion and any systemic therapy that might interfere with the CAR T-cell product 14 days before the infusion.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that B7-H3 CAR T cells are safe for patients. Studies have found that these cells can fight tumors without causing serious side effects. In one trial, patients tolerated the treatment well, even with multiple doses.

Other research has tested B7-H3 CAR T cells on various tumor types. These studies found the treatment to be generally safe, without harming healthy tissues.

B7-H3 is a protein found in many tumors, making it a good target for CAR T cells. Although this is an early-stage trial, current evidence suggests that B7-H3 CAR T cells are safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pediatric cancer, which often include chemotherapy and radiation, B7-H3 CAR T-cell therapy works by reprogramming the patient's own immune cells to specifically target cancer cells. This therapy is unique because it focuses on the B7-H3 protein, a molecule commonly found on cancer cells but not on most normal cells, allowing for a more precise attack on the cancer. Researchers are excited about this approach because it offers the potential for fewer side effects compared to traditional treatments and represents a highly targeted method to eliminate cancer cells.

What evidence suggests that B7-H3 CAR T cells might be an effective treatment for pediatric cancer?

Research has shown that a new treatment called B7-H3 CAR T cells, which participants in this trial will receive, shows promise against solid tumors in children. These specially designed cells can locate and attack cancer cells, as demonstrated in lab tests and animal studies. For example, in one study, mice treated with B7-H3 CAR T cells lived longer. Another study found these cells to be highly effective in fighting tumors in various childhood cancers, such as osteosarcoma. Although human trial data remains limited, early results suggest that the treatment is safe and potentially effective. ^{1 3 6 7 8}

Who Is on the Research Team?

Chris DeRenzo, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults (≤21 years old) with certain solid tumors that have come back or didn't respond to treatment. Participants must have a life expectancy of more than 8 weeks, a performance score ≥50, good heart function, adequate kidney and lung function, not be pregnant or breastfeeding, agree to use birth control methods if applicable, and have an available T-cell product made from their own cells.

Inclusion Criteria

I am not pregnant or breastfeeding and can undergo or have had apheresis.

My tumor is B7-H3 positive and can be measured.

I am 21 years old or younger.

Exclusion Criteria

I haven't taken any medication in the last 14 days that could affect my upcoming CAR T-cell therapy.

I do not have any severe, uncontrolled infections.

I haven't taken high doses of steroids in the week before my planned CAR T-cell therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Collection and Manufacturing

Collection of T cells from participants and manufacturing of B7-H3-CAR T cells

4-6 weeks

Treatment

Participants receive lymphodepleting chemotherapy followed by a single infusion of B7-H3-CAR T cells

6 weeks

Multiple visits for chemotherapy and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Long-term follow-up

Participants enroll in an institutional long-term follow-up protocol

1 year

What Are the Treatments Tested in This Trial?

Interventions

• B7-H3 CAR T cells
• Cyclophosphamide
• Fludarabine
• MESNA

Trial Overview The trial tests B7-H3-CAR T cell therapy in pediatric patients with relapsed/refractory solid tumors expressing B7-H3. It aims to find the highest safe dose of these genetically modified T cells after chemotherapy that depletes lymphocytes (a type of white blood cell).

How Is the Trial Designed?

Group I: Treatment Phase Experimental Treatment 4 Interventions

During the treatment phase, the participant receives an infusion of the B7-H3-CAR T cells that were made in the Collection and Manufacturing Phase. Chemotherapy is given for several days prior to the cellular infusion. Patients are then monitored for possible side effects, as well as effects of the treatment on their cancer.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

CAR T cell therapy shows promise for pediatric patients with relapsed or refractory malignancies, emphasizing the importance of patient selection and coordination in the treatment process.

Effective management of toxicities following CAR T cell infusion is crucial for the safety and success of this immunotherapy, highlighting the need for nursing staff to be well-informed about these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization of CAR T Cell Therapy in Pediatric Patients. Szenes, V., Curran, KJ.[2020]

CAR-T cell therapy shows promise in treating relapsed or refractory malignancies, particularly in hematological cancers like acute B-cell lymphoblastic leukemia and B-cell lymphomas, with ongoing research into its application for solid tumors.

This systematic review aims to comprehensively assess the safety and efficacy of CAR-T cell therapy by analyzing various studies, focusing on outcomes such as complete response rates and adverse events, to better understand its potential risks and benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with haematological and solid malignancies: protocol for a systematic review and meta-analysis. Grigor, EJM., Fergusson, DA., Haggar, F., et al.[2019]

Atypical teratoid/rhabdoid tumors (ATRTs) express the B7-H3 protein, which is crucial for their growth and can be targeted for therapy, highlighting its potential as a therapeutic target for this aggressive pediatric cancer.

Using B7-H3-targeted CAR T cells delivered directly into the brain showed faster and more effective tumor suppression in mouse models compared to traditional intravenous delivery, suggesting that localized treatment may reduce systemic side effects and improve outcomes for children with ATRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors. Theruvath, J., Sotillo, E., Mount, CW., et al.[2022]

B7-H3 is a promising target for immunotherapy in pediatric solid tumors, as it is highly expressed in cancers like neuroblastoma and rhabdomyosarcoma but low in normal tissues, making it a safe target for treatment.

Research shows that targeting B7-H3 with antibody-drug conjugates and CAR-T cells can significantly reduce tumor growth and improve anti-tumor immune responses in preclinical models, indicating strong potential for effective therapies in children with these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting B7-H3-A Novel Strategy for the Design of Anticancer Agents for Extracranial Pediatric Solid Tumors Treatment. Rasic, P., Jeremic, M., Jeremic, R., et al.[2023]

B7-H3 CAR T cells have shown significant antitumor activity in various pediatric solid tumor models, including osteosarcoma and medulloblastoma, indicating their potential as a treatment option for relapsed pediatric malignancies.

The effectiveness of B7-H3 CAR T cells is linked to the density of the B7-H3 antigen on tumor cells, suggesting that this therapy could be selectively effective against tumors with high antigen expression while minimizing effects on normal tissues with lower expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors. Majzner, RG., Theruvath, JL., Nellan, A., et al.[2021]

CAR T-cell therapy has shown high response rates in treating relapsed/refractory B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) in children, but the effects are often of limited duration, highlighting the need for improved persistence and strategies to prevent relapse.

There are significant challenges in applying CAR T-cell therapy to other pediatric malignancies like acute myeloid leukaemia (AML) and solid tumors, necessitating further research into alternative targets and combination therapies to enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paediatric Strategy Forum for medicinal product development of chimeric antigen receptor T-cells in children and adolescents with cancer: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration. Pearson, AD., Rossig, C., Mackall, C., et al.[2023]

In a study involving 1,926 subjects from 17 clinical trials, patients with acute lymphocytic leukemia (ALL) were found to have a higher risk of severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX) compared to those with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM).

The use of CAR T cells produced with gammaretrovirus vectors containing CD28 sequences was linked to increased rates of sNTX, while administering cytokine-directed therapies and corticosteroids at lower toxicity grades was associated with reduced rates of sCRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. Foster, M., Negash, Y., Eberhardt, L., et al.[2022]

An 11-year-old girl with relapsed acute B lymphoblastic leukemia (B-ALL) was treated with fourth generation CD19 CAR-T therapy, which was found to be effective and safe, resulting in a negative minimal residual disease after treatment.

Despite initial success and 10 months of disease-free survival, the patient ultimately relapsed due to increasing TEL-AML1 gene copies, highlighting the need for ongoing monitoring and potential further interventions in CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chimeric antigen receptors T cells in treatment of a relapsed pediatric acute lymphoblastic leukemia, relapse after allogenetic hematopoietic stem cell transplantation: case report and review of literature review]. Zuo, Y., Wang, J., Lu, A., et al.[2020]

CAR-T cell therapy, while currently approved only for B cell malignancies, shows promising potential for treating pediatric brain tumors, with early clinical trials indicating some positive responses.

Recent preclinical studies have identified new tumor antigens and combination strategies that enhance the effectiveness of CAR-T cells, particularly when administered directly to the tumor site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cells for pediatric brain tumors: Present and future. Leruste, A., Beccaria, K., Doz, F.[2021]

CAR-modified T-cell therapy targeting CD19 has shown impressive remission rates of 50% to 60% at 1 year for patients with relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL), marking a significant advancement in treatment for this challenging condition.

While the therapy is effective, it can lead to side effects such as cytokine release syndrome (CRS) and neurotoxicity shortly after treatment, as well as long-term B-cell aplasia, which are important considerations for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapy Clinical Results in Pediatric and Young Adult B-ALL. DiNofia, AM., Maude, SL.[2020]

B7-H3 is widely expressed in various human solid tumors but has limited expression in normal tissues, making it a promising target for CAR T-cell therapy.

Combining B7-H3.CAR T cells with the epigenetic drug SAHA significantly boosts their ability to kill solid cancer cells, suggesting this combination could improve treatment outcomes in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3-Specific CAR T Cells in Solid Tumors. Lei, X., Ou, Z., Yang, Z., et al.[2022]

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. 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.

3. 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 ...

4. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A364

315 Improving pediatric neuroblastoma ... Mice treated with B7-H3 CAR-Ts alone showed a median survival of 82 days, with one mouse surviving disease-free past 130 days. In contrast, all ...

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

Therapeutic Efficacy of B7-H3 CAR T Cell Therapy In ... We evaluated the capability of B7-H3 CAR T cells to eliminate KNS-42 cells through in vitro testing. Our results after 72 hours of co-culture ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39255444/

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

7. 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 ...

8. link.springer.com link.springer.com/article/10.1007/s10555-025-10294-y

B7-H3 in the tumor microenvironment: Implications for CAR ... This selective expression makes B7-H3 an attractive, widely applicable target for CAR T cells and other cell-surface directed therapeutics.