Immunotherapy + Chemotherapy for Uveal Melanoma

Overseen By Sapna P. Patel

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Non-oncology vaccines

Disqualifiers: Cardiovascular disease, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: 103

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for uveal melanoma that has spread to other parts of the body. It combines personalized immune therapy, where T cells (a type of white blood cell) from the patient's own body are trained to fight melanoma, with chemotherapy and other immune-boosting drugs, including Aldesleukin (an immunotherapy drug also known as Interleukin-2 or Proleukin). The goal is to find the best dose, check for side effects, and determine the effectiveness of this combination against the cancer. People with metastatic uveal melanoma, especially those with frequent recurrences, might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that steroids at doses higher than 10 mg are not allowed 3 days before and during the T cell infusion. You also cannot be on other cancer treatments aside from those in the study.

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

Research shows that each treatment in this study has some safety data in humans, though side effects are possible. Here is a breakdown:

1. **Aldesleukin**: High doses of aldesleukin can cause serious side effects, including life-threatening reactions. One study found that 4% of patients experienced fatal side effects. While it can be effective, close monitoring is essential.

2. **Autologous CD8+ SLC45A2-specific T Lymphocytes**: This cell therapy has been found safe and well-tolerated in patients with advanced uveal melanoma, suggesting that any side effects are manageable.

3. **Cyclophosphamide**: This drug can cause side effects like nausea, hair loss, and a weakened immune system. Long-term issues such as infertility or secondary cancers may also occur, necessitating careful use.

4. **Ipilimumab**: Ipilimumab is considered a reasonable option for those with advanced uveal melanoma. Common side effects include tiredness, diarrhea, and skin rash. Severe immune-related effects can occur and need attention.

Overall, while these treatments have known safety profiles, they can still cause significant side effects. Participants in trials should be aware and discuss potential risks with healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for uveal melanoma because it combines immunotherapy and chemotherapy in a novel way. Unlike standard treatments, which often rely on surgery, radiation, or traditional chemotherapy alone, this approach uses a patient's own modified T-cells to target cancer cells specifically. The unique use of autologous CD8+ SLC45A2-specific T lymphocytes, delivered directly to the liver via hepatic arterial infusion, offers a targeted attack on tumor cells. Additionally, the combination with aldesleukin and ipilimumab may enhance the immune system's ability to fight cancer, potentially leading to more effective and durable responses.

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

In this trial, participants will receive a combination of treatments to target advanced uveal melanoma. Research has shown that using a patient's own immune cells, specifically CD8+ T cells, can help target melanoma cells. This method involves training these T cells to attack cancer cells. Early studies suggest that these trained cells can persist in the body and effectively target tumors. Cyclophosphamide, a chemotherapy drug included in this trial, may help by slowing tumor growth. Aldesleukin, also part of the trial, can boost the immune system to better fight cancer. Additionally, Ipilimumab, an immunotherapy drug used in this trial, has effectively treated advanced uveal melanoma by aiding the immune system in attacking cancer. Together, these treatments aim to strengthen the body's defense against cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Sapna P. Patel

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with metastatic uveal melanoma. They must have measurable disease, specific human leukocyte antigen types, and be in good physical condition (ECOG/Zubrod status of 0-1). Women who can bear children and men must use contraception. Patients should not have significant heart issues or other conditions that could complicate treatment.

Inclusion Criteria

I am fully active or can carry out light work.

It has been over 4 weeks since my last cancer treatment or major surgery.

Your hematocrit level is at least 24% or your hemoglobin level is at least 8 g/dL.

Exclusion Criteria

I have another cancer type but it doesn't need treatment right now.

You have tested positive for HIV, Hepatitis B, or Hepatitis C.

You have received another type of immunotherapy treatment that the principal investigator believes would not be safe to combine with this study's treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Patients receive cyclophosphamide intravenously over 30-60 minutes on day -2

1 day

1 visit (in-person)

T-Cell Infusion

Patients receive autologous CD8+ SLC45A2-specific T lymphocytes via hepatic arterial infusion and aldesleukin subcutaneously for 14 days

14 days

Daily visits for 14 days

Post T-Cell Infusion

Patients receive ipilimumab intravenously on days 1, 22, 43, and 64

64 days

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up at days 84 and 168, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Aldesleukin
• Autologous CD8+ SLC45A2-specific T Lymphocytes
• Cyclophosphamide
• Ipilimumab

Trial Overview The trial tests a combination of treatments: autologous CD8+ T lymphocytes tailored to target melanoma cells, cyclophosphamide chemotherapy, aldesleukin biological therapy, and ipilimumab immunotherapy. The goal is to see if this mix works better for treating metastatic uveal melanoma.

How Is the Trial Designed?

Group I: Treatment (cyclophosphamide, T-cells, aldesleukin, ipilimumab) Experimental Treatment 4 Interventions

PREPARATIVE REGIMEN: Patients receive cyclophosphamide IV over 30-60 minutes on day -2. T-CELL INFUSION: Patients receive autologous CD8+ SLC45A2-specific T lymphocytes via hepatic arterial infusion via central catheter over 60 minutes on day 0. Within 6 hours of T-cell infusion, patients also receive aldesleukin BID SC for 14 days in the absence of disease progression or unacceptable toxicity. POST T-CELL INFUSION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 in the absence of disease progression or unacceptable toxicity.

Aldesleukin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Proleukin for:

• Metastatic renal cell carcinoma
• Metastatic melanoma

Approved in European Union as Proleukin for:

• Metastatic renal cell carcinoma

Approved in Canada as Proleukin for:

• Metastatic renal cell carcinoma
• Metastatic melanoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 39 patients with uveal melanoma treated with ipilimumab, the overall response rate was low at 2.6%, but the combined response plus stable disease rate was 46% at 12 weeks, indicating some potential for disease stabilization.

Ipilimumab was associated with significant immune-related adverse events in 71.8% of patients, with more severe events occurring in those receiving higher doses, but the treatment was deemed to have manageable toxicity and a median overall survival of 9.6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience. Luke, JJ., Callahan, MK., Postow, MA., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5604296/

High-dose interleukin-2 (HD IL-2) for advanced melanoma Results · PFS and OS analyses. The primary analysis of 243 patients revealed a median OS of 9.6 months (95% CI, 7.4 to 11.2 months) in the entire ...

2. curemelanoma.org curemelanoma.org/blog/clinical-trials-to-watch-july-2025

Melanoma Clinical Trials to Watch: July 2025 The goal of phase 2 and phase 3 trials is to collect data on the treatment's effectiveness, safety, and side effects in larger numbers of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5767160/

Clinical outcomes in metastatic uveal melanoma treated with ... Antibodies inhibiting the programmed death receptor 1 (PD-1) have shown significant activity in the treatment of advanced cutaneous melanoma.

4. curemelanoma.org curemelanoma.org/patient-eng/melanoma-treatment/options/interleukin-2-il-2-aldesleukin-proleukin

Interleukin-2 (IL-2, Aldesleukin, PROLEUKIN®) Discover how high-dose IL-2 (Proleukin) supports melanoma treatment by boosting immune response. Learn who benefits and what to expect.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03467516

Study Details | NCT03467516 | Adoptive Transfer of Tumor ... Metastatic uveal melanoma (UM) carries a poor prognosis with estimated survival of 4-6 months. There are no known effective systemic therapies. Metastatic UM is ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6889624/

High dose interleukin-2 (Aldesleukin) - expert consensus on ... Retrospective analysis of the safety and efficacy of interleukin-2 after prior VEGF-targeted therapy in patients with advanced renal cell carcinoma. J ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/103293s5130lbl.pdf

Proleukin (aldesleukin) injection label - accessdata.fda.gov The rate of drug-related deaths in the 255 metastatic RCC patients who received single- agent Proleukin® (aldesleukin) was 4% (11/255); the rate of drug-related ...

8. curemelanoma.org curemelanoma.org/blog/clinical-trials-to-watch-january-2025

Clinical Trials to Watch: January 2025 Despite the possible anti-tumor benefits, HD IL-2 can cause potentially life-threatening toxicities and patients receiving this treatment need ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8280448/

Clinical Trials in Metastatic Uveal Melanoma: Immunotherapy There is a rising number of immunotherapy clinical trials for patients with UM/MUM, including checkpoint inhibition, vaccines, and T-cell therapies.

10. clinicaltrials.gov clinicaltrials.gov/study/NCT00058279

Monoclonal Antibody Therapy and Interleukin-2 in Treating ... Combining monoclonal antibody therapy with interleukin-2 may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining monoclonal ...