Lymphodepletion + Adoptive Cell Transfer with High Dose IL-2 for Melanoma

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Infections, HIV, Hepatitis, Autoimmune, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treat melanoma, a type of skin cancer. It uses a treatment called adoptive cell transfer combined with high doses of a protein called IL-2, which boosts the immune system's ability to fight cancer. Additionally, the trial includes lymphodepletion, a preparatory step to enhance the effectiveness of adoptive cell transfer. The study examines whether this method can be safe and remain effective in the body over time. People with melanoma that has spread and remains measurable might be suitable for this trial, especially if they have undergone surgery to remove some but not all of their cancer. As an unphased trial, this study offers patients the opportunity to contribute to innovative research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on chronic immunosuppressive medications or systemic steroids, you may not be eligible to participate.

What prior data suggests that this treatment is safe for melanoma?

Research has shown that using Tumor-Infiltrating Lymphocytes (TIL) with High Dose Interleukin-2 (IL-2) is generally safe, though some side effects occur. TIL therapy has specific side effects, but doctors can manage them with supportive care.

For High Dose IL-2, studies indicate its safe use in melanoma patients, even those with brain metastases. Some patients respond well to this treatment. While risks exist, selecting the right patients can enhance safety.

Both treatments show promise but require managing side effects. Participants should discuss expectations with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for melanoma, which often involve surgery, radiation, or chemotherapy, this treatment uses a unique approach called Adoptive Cell Transfer (ACT). ACT works by harnessing the patient's own immune cells, specifically T cells, and infusing them back into the body to fight cancer. Researchers are excited about this method because it directly empowers the immune system to target and destroy melanoma cells. Additionally, the use of high dose IL-2 helps to boost the activity and persistence of these T cells, potentially leading to more effective and lasting responses against the cancer. This combination represents a promising shift towards personalized and immune-based cancer therapies.

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

Research has shown that using a patient's own immune cells combined with a high dose of IL-2 (a protein that boosts the immune system) can effectively treat melanoma. In this trial, participants will receive this combination treatment, which studies have shown results in significant tumor shrinkage in 55% of melanoma patients. This treatment is generally safe, with manageable side effects. High-dose IL-2 remains effective even when other treatments fail, making it a promising option for people with advanced melanoma. ^{2 3 6 7 8}

Who Is on the Research Team?

Amod Sarnaik, M.D.

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma, either untreated or previously treated. They can have up to 3 brain metastases if certain conditions are met. Participants need good organ function and a performance status indicating they're mostly active. Pregnant women, those with severe infections, blood clotting issues, autoimmune diseases needing steroids, or significant psychiatric illness cannot join.

Inclusion Criteria

I have allergies to antibiotics, but I understand the treatment minimizes exposure.

I have TILs stored from a previous trial that meet the current trial's criteria.

I have brain metastases treated with surgery or radiation.

Exclusion Criteria

I need to take steroids every day for my immune system.

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

I have an autoimmune disease and take medication to suppress my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive cyclophosphamide and fludarabine to reduce normal lymphocytes

7 days

Daily visits for drug administration

TIL Infusion

Tumor infiltrating lymphocytes (TIL) are infused into the patient

1 day

1 visit (in-person)

High Dose IL-2 Treatment

Participants receive high dose IL-2 every 8-16 hours for up to 15 doses

5 days

Multiple visits (in-person) for IL-2 administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Administration of Lymphodepletion
• Adoptive Cell Transfer
• High Dose IL-2

Trial Overview The study tests a combination of treatments: lymphodepletion (weakening the immune system), adoptive cell transfer (injecting immune cells), high dose IL-2 (a substance that activates immune cells), and surgery on patients with metastatic melanoma to see if this improves treatment outcomes.

How Is the Trial Designed?

Group I: TIL With High Dose IL-2 Experimental Treatment 4 Interventions

Day -7 and -6: Cyclophosphamide 60 mg/kg/day I.V. in 250 ml NS over approximately 2 hours. Mesna 20 mg/kg with D5W or NS at 125 ml/hour infused intravenously over 24 hours. Day -5 to Day -1: Fludarabine 25 mg/m\^2 intravenous piggyback (IVPB0 daily over approximately 30 minutes for 5 days. Day 0: T cell infusion in 250-1000 ml NS over approximately 15-60 minutes depending on volume to be infused. Days 1-5: High dose IL-2, 720,000 IU/kg IV bolus (about 15 minutes) every 8-16 hours for up to 15 doses, beginning approximately 12-16 hours after T cell infusion.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Published Research Related to This Trial

In a pilot study involving 6 patients with metastatic melanoma, the combination of tumor-infiltrating lymphocyte (TIL) therapy and low-dose IL-2 injections resulted in significant reductions in treatment-related toxicity, with no severe adverse events reported.

The treatment led to objective clinical responses in 2 patients, with ongoing complete responses lasting over 10 months, suggesting that low-dose IL-2 can enhance the safety and efficacy of adoptive cell therapy for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. Ellebaek, E., Iversen, TZ., Junker, N., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12128428/

Role of high-dose interleukin-2 for melanoma in the age of ... Retrospective data demonstrate that HD IL-2 can be used safely after ICI failure, and its modest efficacy is retained. In a retrospective ...

2. astctjournal.org astctjournal.org/article/S2666-6367(24)00784-X/fulltext

The Clinical TIL Experience in Melanoma: Past, Present ... Objective responses were observed in 11 of 20 treated patients, leading to an objective response rate (ORR) of 55%. This included 9 responses among 15 IL-2 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0923753425001358

Review Safety of adoptive therapy with tumor-infiltrating ... This meta-analysis examined the safety of TIL-ACT therapy along with HD-IL-2, in advanced melanoma patients. · TIL-ACT presents a safe and manageable toxicity ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02621021

NCT02621021 | A Phase 2 Trial for Metastatic Melanoma ... A Phase 2 Trial for Metastatic Melanoma Using Adoptive Cell Therapy With Tumor Infiltrating Lymphocytes Plus IL-2 Either Alone or Following the Administration ...

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

Safety of adoptive therapy with tumor-infiltrating ... This meta-analysis examined the safety of TIL-ACT therapy along with HD-IL-2, in advanced melanoma patients. •. TIL-ACT presents a safe and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40210086/

Safety of adoptive therapy with tumor-infiltrating ... TIL-ACT, a new approved and promising therapy for melanoma patients, presents a distinctive toxicity profile that is currently manageable with supportive care ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6028054/

Outcomes of adoptive cell transfer with tumor-infiltrating ... We found that ACT with TIL can eliminate small melanoma brain metastases. However, following TIL therapy these patients frequently progress in the brain at a ...

8. onclive.com onclive.com/view/tumor-infiltrating-lymphocyte-therapy-tackles-treatment-blind-spot-in-advanced-melanoma

Tumor-Infiltrating Lymphocyte Therapy Tackles Treatment ... ACT with TILs showed objective response rates (ORRs) between 31% and 35% in findings from an early clinical trial from 1994 in patients with ...