TIL Therapy for Pediatric Cancer

Recruiting at 1 trial location

Overseen By Jade Hanson

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Infections, HIV, Hepatitis, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using Tumor-Infiltrating Lymphocytes (TIL therapy) to address high-risk solid tumors in children and young adults. The first part of the study creates a TIL product from these tumors, while the second part assesses the safety of TIL therapy combined with chemotherapy and Interleukin-2, a type of immunotherapy. This trial is open to young patients with certain aggressive cancers outside the central nervous system, such as high-risk neuroblastoma or metastatic Ewing sarcoma, who have not responded to initial treatments or are at high risk of relapse. 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.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on chronic immunosuppressive steroids or receive other anti-cancer or investigational therapies during the trial.

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

Research shows that Tumor-Infiltrating Lymphocyte (TIL) therapy, combined with specific chemotherapy and Interleukin-2, holds promise for treating serious childhood solid tumors. Studies indicate that this combination can be safe for children with high-risk tumors.

Earlier studies tested TIL therapy in other cancers, such as non-small cell lung cancer, and found positive results regarding safety and effectiveness. The body can handle the treatment without many serious side effects.

Currently, researchers are studying TIL therapy for its safety and potential benefits in treating various solid tumors. While more research is needed, existing evidence suggests it can be a safe option for children facing these challenging cancers. ^{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, radiation, and surgery, Tumor Infiltrating Lymphocytes (TIL) therapy takes a different approach by harnessing the body's own immune cells to fight cancer. Researchers are excited about TIL therapy because it involves extracting immune cells from a patient's tumor, growing them in large numbers, and reintroducing them to attack cancer cells more effectively. This method potentially offers a more personalized and targeted treatment option, which could lead to better outcomes with fewer side effects than traditional therapies.

What evidence suggests that TIL therapy might be an effective treatment for pediatric cancer?

This trial will evaluate TIL therapy for pediatric cancer. Studies have shown that tumor-infiltrating lymphocytes (TILs) can effectively treat certain adult cancers, like metastatic melanoma, and may also work for children's solid tumors. Research indicates that TIL therapy uses a patient's own immune cells, taken from the tumor, expanded in number, and then reintroduced into the body to help fight cancer. Previous patients demonstrated that TILs can be successfully grown from children's tumors, supporting their potential use in kids. Although more data is needed for children, early signs are promising, suggesting TIL therapy could be a valuable treatment option for high-risk solid tumors in children. ^{1 5 6 7 8}

Who Is on the Research Team?

Jonathan Metts, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1 to 21 with high-risk solid tumors outside the brain. They must have recovered from previous cancer treatments, meet organ function requirements, and not be pregnant or nursing. Participants need a Karnofsky/Lansky score of at least 60%, no active infections requiring IV antibiotics, no CNS metastases history, and cannot be on other cancer therapies.

Inclusion Criteria

You have verified the availability of an acceptable TIL cellular product.

This is a prospective biobanking research study.

I am scheduled for an open surgical biopsy or resection for my tumor.

Exclusion Criteria

Sexually active patients of reproductive potential are eligible if they have agreed to use an effective contraceptive method from the time of informed consent through the duration and for 1 month following completion of protocol treatment. The definition of an effective contraceptive method will be at the discretion of the institutional investigator.

I am not on long-term steroids for immune suppression.

I have or had brain metastases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Biobanking

Feasibility of creating Tumor-Infiltrating Lymphocyte (TIL) product from high-risk pediatric solid tumors

3 years

Treatment

TIL therapy with lymphodepleting chemotherapy and Interleukin 2

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• Interleukin-2
• Tumor Infiltrating Lymphocytes

Trial Overview The study has two parts: first to see if it's possible to make TIL (Tumor-Infiltrating Lymphocyte) products from pediatric tumors; second to test the safety of TIL therapy combined with lymphodepleting chemo drugs Fludarabine and Cyclophosphamide followed by Interleukin-2 in these patients.

How Is the Trial Designed?

Group I: TIL Therapy Experimental Treatment 1 Intervention

TIL therapy with lymphodepleting chemotherapy and Interleukin 2

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Johns Hopkins All Children's Hospital

Lead Sponsor

Trials

47

Recruited

5,009,000+

Cannonball Kids Cancer Foundation

Collaborator

Trials

1

Recruited

30+

Swim Across America

Collaborator

Trials

11

Recruited

410+

Benjamin Gilkey Fund

Collaborator

Trials

1

Recruited

30+

Swim Across America Foundation

Collaborator

Trials

1

Recruited

30+

Cannonball Kids' Cancer Foundation

Collaborator

Trials

6

Recruited

140+

Published Research Related to This Trial

A study analyzing tumor-infiltrating lymphocytes (TILs) from 11 breast cancer biopsies revealed that CD4+ TILs have distinct T cell receptor (TCR) characteristics compared to CD8+ TILs, including larger sequences and a higher usage of positively charged residues.

The CD4+ TILs exhibited a more restricted TCR repertoire with greater similarity among sequences, suggesting a potential tumor-driven adaptation that may enhance their ability to recognize and respond to cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of tumor infiltrating CD4+ and CD8+ CDR3 sequences reveals shared features putatively associated to the anti-tumor immune response. Aran, A., Lázaro, G., Marco, V., et al.[2023]

A retrospective analysis of 21 patients with advanced cutaneous melanoma showed that nonselected autologous tumor-infiltrating lymphocytes (TILs) resulted in a high overall response rate of 67% and a complete response rate of 19%, indicating significant efficacy even in patients who had previously undergone PD-1 inhibition.

The treatment was found to be safe, with no treatment-related deaths and a median overall survival of 21.3 months, suggesting that TIL therapy could be a promising option for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma. Pillai, M., Jiang, Y., Lorigan, PC., et al.[2022]

Tumor-infiltrating lymphocytes (TIL) have shown to be significantly more effective than other immune cells in treating advanced metastatic tumors, with successful expansion from 24 out of 25 human tumors, including various types of cancers.

The method developed for large-scale expansion of TIL resulted in generating over 10 billion lymphocytes in some cases, and clinical trials using these expanded TIL for treating metastatic disease have already commenced.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. Topalian, SL., Muul, LM., Solomon, D., et al.[2020]

In a study analyzing tumor-infiltrating lymphocytes (TILs) from metastatic melanoma patients, neoantigen-specific CD4+ T cells were found to be crucial, showing effective responses against tumors, even in non-responders.

The research highlights the need to focus on neoantigen-specific CD4+ T cells in adoptive cell therapy (ACT) protocols, as they can enhance antitumor immunity and provide a potent source of tumor-specific effectors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoantigen-specific CD4+ tumor-infiltrating lymphocytes are potent effectors identified within adoptive cell therapy products for metastatic melanoma patients. Hall, MS., Teer, JK., Yu, X., et al.[2023]

In a study of 10 patients with advanced melanoma treated with autologous tumor-infiltrating lymphocytes (TILs) and interleukin-2 (IL-2), no serious adverse effects were reported, indicating a favorable safety profile for this immunotherapy approach.

Among the patients, there were instances of complete and partial remission, with one patient surviving for 9 years post-treatment, suggesting potential long-term benefits; however, the presence of certain T cell types was associated with shorter overall survival, highlighting the need for further research into optimizing treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients. Saint-Jean, M., Knol, AC., Volteau, C., et al.[2021]

In a study involving 55 patients with various cancers, including melanoma, renal cell carcinoma, and colorectal cancer, only one patient showed an objective tumor response, indicating limited efficacy of tumor-infiltrating lymphocytes (TIL) as a treatment.

Patients receiving a higher dose of TIL (mean = 54.4 x 10^9) had a median survival of 11.8 months, suggesting a potential dose/benefit relationship, although overall response rates were not encouraging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-infiltrating lymphocytes and interleukin-2: dose and schedules of administration in the treatment of metastatic cancer. Dillman, R., Schiltz, P., DePriest, C., et al.[2006]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9847472/

Adoptive Cellular Therapy for Pediatric Solid Tumors Children and adolescents with high-risk (metastatic and relapsed) solid tumors have poor outcomes despite intensive multimodal therapy, and there is a pressing ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324924008259

Expansion of tumor-infiltrating and marrow ... TIL and MIL expansion from pediatric solid tumors was successful, including the full-scale expansion process. This data supports translation to an ACT-TIL ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11393248/

Recent clinical researches and technological development in ... In this comprehensive review, we aim to elucidate the remarkable potential of TIL therapy by delving into recent advancements in basic and clinical researches.

4. withpower.com withpower.com/trial/phase-1-neoplasms-11-2023-3b5e3

TIL Therapy for Pediatric Cancer Research shows that tumor-infiltrating lymphocytes (TILs) have been effective in treating certain adult cancers, like metastatic melanoma, and have potential in ...

5. vcm.edpsciences.org vcm.edpsciences.org/articles/vcm/full_html/2025/01/vcm20250003/vcm20250003.html

Tumor-infiltrating lymphocyte therapy: therapeutic advances ... The net efficacy of TIL therapy thus results from a careful choreography: the patient is lymphodepleted, a large number of partially rejuvenated T cells with ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2025-04759

Tumor Infiltrating Lymphocytes for the Treatment of ... Giving TIL with lymphodepleting chemotherapy and post infusion IL-2 may be safe, feasible and/or effective in treating children with high risk solid tumors.

7. astctjournal.org astctjournal.org/article/S2666-6367(24)00783-8/fulltext

Tumor-Infiltrating Lymphocyte Therapy: A New Frontier This trial indicated that TIL therapy could achieve durable and meaningful responses in NSCLC, including in the important subset of never-smoker lung cancer ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05141474

Study Details | NCT05141474 | Assessment of the Safety ... To evaluate the safety and the tolerability of ex vivo next generation neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) in patients with metastatic or ...