Immunotherapy + Chemotherapy for Uveal Melanoma

Overseen By Sapna P. Patel

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

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

Compensation: Varies

Number of Visits: 103

34 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib trial studies the side effects and best dose of autologous CD8 positive (+) SLC45A2-specific T lymphocytes when given together with cyclophosphamide, aldesleukin, and ipilimumab, and to see how well they work in treating patients with uveal melanoma that has spread to other places in the body (metastatic). To make specialized CD8+ T cells, researchers separate out T cells collected from patients' blood and treat them so they are able to target melanoma cells. The blood cells are then given back to the patients. This is known as "adoptive T cell transfer" or "adoptive T cell therapy." Drugs used in chemotherapy, such as cyclophosphamide, may work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Biological therapies, such as aldesleukin, use substances made from living organisms that may stimulate the immune system in different ways and stop tumor cells from growing. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving autologous CD8+ SLC45A2-specific T lymphocytes together with cyclophosphamide, aldesleukin, and ipilimumab may work better in treating patients with metastatic uveal melanoma.

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.

What data supports the effectiveness of the treatment Immunotherapy + Chemotherapy for Uveal Melanoma?

Research shows that immunotherapy, including drugs like ipilimumab, has been used effectively in other types of melanoma, such as cutaneous melanoma, and has shown promise in uveal melanoma by potentially improving survival rates. Additionally, studies suggest that vaccines targeting specific immune cells can activate the body's immune response against uveal melanoma, indicating potential effectiveness of immunotherapy in this condition. ^{1 2 3 4 5}

What safety data exists for immunotherapy and chemotherapy in treating uveal melanoma?

Immunotherapy drugs like Ipilimumab can cause immune-related side effects, including skin, liver, and eye issues, with eye problems being rare but potentially serious. Some patients have experienced severe eye inflammation and other immune-related complications, which can be managed with medications like corticosteroids. It's important to monitor for these side effects and manage them promptly to prevent long-term damage. ^{6 7 8 9 10}

How is the treatment for uveal melanoma with Aldesleukin, Autologous CD8+ SLC45A2-specific T Lymphocytes, Cyclophosphamide, and Ipilimumab different from other treatments?

This treatment is unique because it combines immunotherapy and chemotherapy, using a personalized approach with autologous (patient's own) CD8+ T cells that target specific tumor antigens, alongside drugs like Ipilimumab, which is known for its role in enhancing immune response against melanoma. ^{1 2 5 11 12}

Research Team

Sapna P. Patel

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Characterization of CD4+ T cells primed and boosted by MHCII primary uveal melanoma cell-based vaccines. [2020]

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

MHC class II-transduced tumor cells originating in the immune-privileged eye prime and boost CD4(+) T lymphocytes that cross-react with primary and metastatic uveal melanoma cells. [2017]

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

Circulating immune profile can predict survival of metastatic uveal melanoma patients: results of an exploratory study. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Adjuvant Ipilimumab in High-Risk Uveal Melanoma. [2020]

5. United States 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. [2022]

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

Severe Ocular Myositis After Ipilimumab Treatment for Melanoma: A Report of 2 Cases. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Neuromyelitis Optica After Treatment of Uveal Melanoma With Nivolumab and Ipilimumab. [2022]

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

Toxicities Associated With PD-1/PD-L1 Blockade. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Ophthalmic immune-related adverse events associated with immune checkpoint inhibitors. [2023]

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

Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD), and human leukocyte interferon for metastatic uveal melanoma. [2015]

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

Long overall survival after dendritic cell vaccination in metastatic uveal melanoma patients. [2021]