TIL Therapy for Pediatric Cancer

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

Trial Summary

What is the purpose of this trial?

Part One of this study will determine the feasibility of creating Tumor-Infiltrating Lymphocyte (TIL) product prospectively from high-risk pediatric solid tumors. Part Two of this study will determine the safety of TIL therapy with lymphodepleting chemotherapy and post-TIL Interleukin-2 in high-risk pediatric solid tumors

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.

What data supports the effectiveness of this treatment 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 pediatric cancers. Although expanding TILs for therapy in children is challenging, they are known to be powerful anti-tumor cells, suggesting promise for future treatments. ^{1 2 3 4 5}

Is TIL therapy generally safe for humans?

TIL therapy has been studied in patients with advanced melanoma and nasopharyngeal carcinoma, showing no serious adverse effects and no treatment-related deaths. The safety profile is consistent with the use of lymphodepleting chemotherapy and high-dose interleukin-2, which are part of the treatment process. ^{6 7 8 9 10}

How is TIL therapy different from other treatments for pediatric cancer?

TIL therapy (Tumor Infiltrating Lymphocytes therapy) is unique because it uses the patient's own immune cells, specifically T cells, to fight cancer. These cells are extracted from the tumor, expanded in the lab, and then reintroduced into the patient to enhance the body's natural ability to combat cancer, offering a personalized and potentially more effective treatment option compared to traditional therapies. ^{1 2 4 10 11}

Research Team

Jonathan Metts, MD

Principal Investigator

Johns Hopkins All Children's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Roles of Tumor Infiltrating Lymphocytes in Hematologic Malignancies-Review]. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Adoptive Cellular Therapy for Pediatric Solid Tumors: Beyond Chimeric Antigen Receptor-T Cell Therapy. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Phenotypic and functional analysis of lymphocytes infiltrating paediatric tumours, with a characterization of the tumour phenotype. [2019]

4. Switzerland 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. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Tumor-infiltrating lymphocytes and interleukin-2: dose and schedules of administration in the treatment of metastatic cancer. [2006]

6. England pubmed.ncbi.nlm.nih.gov

Neoantigen-specific CD4+ tumor-infiltrating lymphocytes are potent effectors identified within adoptive cell therapy products for metastatic melanoma patients. [2023]

7. Egypt pubmed.ncbi.nlm.nih.gov

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

A phase II randomised controlled trial of adjuvant tumour-infiltrating lymphocytes for pretreatment Epstein-Barr virus DNA-selected high-risk nasopharyngeal carcinoma patients. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Adoptive cellular immunotherapy for childhood malignancies. [2008]