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

19 Participants Needed

Trial Summary

What is the purpose of this trial?

The overall purpose of this research study is to find a better way to treat melanoma. This will be a single arm exploratory trial to evaluate prospectively the feasibility of, the toxicities of, and the persistence of TIL which can survive in vivo.

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 data supports the effectiveness of the treatment Lymphodepletion + Adoptive Cell Transfer with High Dose IL-2 for Melanoma?

Research shows that adoptive cell transfer therapy, especially when combined with high-dose IL-2, has resulted in clinical response rates of 50% or more in patients with metastatic melanoma, indicating significant effectiveness in treating this condition. ^{1 2 3 4 5}

Is the combination of lymphodepletion, adoptive cell transfer, and high-dose IL-2 safe for humans?

The combination of lymphodepletion, adoptive cell transfer, and high-dose IL-2 has been studied in patients with metastatic melanoma. While it has shown significant clinical benefits, it is associated with notable toxicities, particularly due to high-dose IL-2. However, studies using lower doses of IL-2 have reported no unexpected adverse events, suggesting that the treatment can be safe with modified dosing. ^{1 2 4 5 6}

How is the treatment of lymphodepletion and adoptive cell transfer with high dose IL-2 for melanoma different from other treatments?

This treatment is unique because it involves using the patient's own immune cells, which are expanded and activated outside the body, and then reinfused to fight melanoma, combined with high doses of IL-2 to boost the immune response. This approach can lead to higher response rates compared to traditional therapies, but it also comes with significant toxicity challenges. ^{1 2 4 5 7}

Research Team

Amod Sarnaik, M.D.

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

White paper on adoptive cell therapy for cancer with tumor-infiltrating lymphocytes: a report of the CTEP subcommittee on adoptive cell therapy. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy of adoptive therapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 in advanced cutaneous melanoma: a systematic review and meta-analysis. [2023]

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

Immunotherapy for advanced melanoma. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2. [2019]

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

Immunization with interleukin-2 transfected melanoma cells. A phase I-II study in patients with metastatic melanoma. [2012]

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

Successful treatment of melanoma brain metastases with adoptive cell therapy. [2022]