Cell Therapy + Chemo + TBI for Skin Cancer

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Systemic steroids

Disqualifiers: Pregnancy, Infections, Immunodeficiency, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding total body irradiation (TBI) to a cell therapy and chemotherapy mix is more effective for treating metastatic melanoma, a type of skin cancer that has spread to other parts of the body. Participants will receive either cell therapy with chemotherapy alone or with the addition of TBI. Those diagnosed with metastatic melanoma and having a removable tumor for the study might be suitable candidates. The study seeks to identify which combination enhances the immune system's ability to fight the cancer. Regular follow-ups will monitor the cancer's response to the treatment. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to significant advancements in cancer 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 must wait more than four weeks since any prior systemic therapy and six weeks since any anti-CTLA4 antibody therapy before joining the trial.

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

Research has shown that using young tumor-infiltrating lymphocytes (TILs) to treat advanced melanoma is safe and generally well-tolerated. Most side effects arise from chemotherapy and a drug called high-dose aldesleukin, which boosts the immune system. Studies have found these side effects can be managed.

When TIL therapy combines with total body irradiation (TBI), the treatment remains promising. However, reports of serious side effects, including some deaths, have occurred, though these were often not directly caused by the treatment. It's important to understand that while TIL therapy with TBI can be effective, there is a risk of side effects.

Overall, TIL therapy, with or without TBI, is gaining attention for its potential to help patients with advanced melanoma. Anyone considering joining a clinical trial should discuss the possible risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach to fighting skin cancer. Unlike traditional treatments like surgery, radiation, or standard chemotherapy, these new options harness the power of the body's own immune system. The use of young Tumor Infiltrating Lymphocytes (TIL) is a standout feature, as these cells are specially reprogrammed to target and attack cancer cells more effectively. Additionally, the combination with high-dose aldesleukin and the optional use of Total Body Irradiation (TBI) helps to enhance the immune response, potentially leading to better outcomes for patients. This innovative approach could represent a significant advancement in immunotherapy for skin cancer.

What evidence suggests that this trial's treatments could be effective for metastatic melanoma?

Research has shown that young tumor-infiltrating lymphocytes (TIL) can yield positive results for patients with advanced melanoma, a type of skin cancer. In earlier studies, TIL therapy reduced tumors in about 58% of patients, meaning more than half experienced tumor shrinkage. In this trial, one group of participants will receive TIL therapy with chemotherapy. Previous studies showed that patients typically lived about 13.9 months with this combination. Another group will receive TIL therapy with chemotherapy and total body irradiation (TBI). Some studies reported better outcomes with this combination, with about 41.7% of patients surviving for at least two years. These encouraging findings suggest that TIL therapy, especially when combined with TBI, might effectively treat this skin cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Steven A Rosenberg, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults aged 18-66 with metastatic melanoma, able to consent, and have a life expectancy over three months. They must be in good health otherwise, not HIV or hepatitis positive, and have a tumor suitable for cell extraction. Women can't be pregnant/breastfeeding; participants must use birth control during/after the trial.

Inclusion Criteria

You are expected to live for more than three months.

Willing to sign a durable power of attorney.

Able to understand and sign the Informed Consent Document

Exclusion Criteria

My immune system is strong and I don't have infections that occur more often or are more severe because of weakened immunity.

I have undergone cell transfer therapy with intense chemotherapy.

I do not have any active major illnesses or infections affecting my heart, lungs, or immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Chemotherapy

Participants receive a non-myeloablative lymphodepleting chemotherapy regimen with cyclophosphamide and fludarabine over 7 days before cell therapy

7 days

Daily visits for chemotherapy administration

Cell Therapy and IL-2 Administration

Participants receive tumor-infiltrating lymphocytes followed by high-dose aldesleukin every 8 hours for up to 5 days

5 days

Multiple visits for IL-2 administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with regular follow-up visits for at least 5 years

5 years

Regular visits every 3 months for the first year, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Aldesleukin
• Cyclophosphamide
• Fludarabine
• Total Body Irradiation (TBI)
• Young TIL
• Young Tumor Infiltrating Lymphocytes

Trial Overview The study is testing if adding total body irradiation (TBI) to chemotherapy before cell therapy improves outcomes in metastatic melanoma patients. Participants are split into two groups: one receives just chemo while the other gets chemo plus TBI before their own grown white blood cells are reintroduced.

How Is the Trial Designed?

Group I: 2/ACT + TBI Experimental Treatment 5 Interventions

Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young TIL + highdose aldesleukin + TBI

Group II: 1/ACT Experimental Treatment 4 Interventions

Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young TIL + highdose aldesleukin

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2978753/

CD8+ enriched “young” tumor infiltrating lymphocytes can ... Young TIL cultures for therapy were successfully established from 83% of 122 consecutive melanoma patients. Nineteen of 33 patients (58%) treated with CD8+ ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S266663672400784X

Review The Clinical TIL Experience in Melanoma In this review, we highlight key historical data for TIL therapy in melanoma as well as ongoing efforts to improve its efficacy and applicability.

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01497-2/fulltext

Efficacy of TIL therapy in advanced cutaneous melanoma ... Among the 13 patients, median PFS was 5.6 months (95% CI 1.2-8.5 months), and the median OS was 8.8 months (95% CI 7.5 months to NR). Thus, this ...

4. bmjoncology.bmj.com bmjoncology.bmj.com/content/4/1/e000566

Tumour-infiltrating lymphocyte therapy landscape CD8+ Enriched “Young” Tumor Infiltrating Lymphocytes Can Mediate Regression of Metastatic Melanoma. Clin Cancer Res 2010; 16:6122–31. doi ...

5. aacr.org aacr.org/blog/2024/05/29/til-therapy-a-new-melanoma-treatment-30-years-in-the-making/

TIL Therapy: A New Melanoma Treatment 30 Years in the ... Almost two-thirds of patients diagnosed with metastatic melanoma are expected to die within five years, but a newly approved treatment may ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00135-8/fulltext

Safety of adoptive therapy with tumor-infiltrating ... TIL-ACT presents a safe and manageable toxicity profile, with most toxicities arising from chemotherapy and HD-IL-2. •. Further studies with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12272581/

Tumor-infiltrating lymphocytes in melanoma: diagnostic and ... Tumor-infiltrating lymphocytes (TILs) play a significant role in melanoma prognosis and treatment. High TIL density is consistently associated with improved ...

8. cell.com cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00089-8

Safety and efficacy of combined treatment with tumor- ... Tumor-infiltrating lymphocytes (TILs) are effective in the treatment of metastatic melanoma (MM), but toxicity limits its application.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e21508

Safety, tolerance, and preliminary efficacy of autologous ... TIL therapy has demonstrated good safety and tolerability in Chinese patients with advanced melanoma and achieved objective therapeutic effects.

10. clinicaltrials.gov clinicaltrials.gov/study/NCT06566092

NCT06566092 | Study of Autologous Tumor-Infiltrating ... This study is planned to test the safety and tolerability of the TIL regimen. The study will also test how well TIL fights cancer.