Immunotherapy + Adoptive Cell Therapy for Melanoma

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressive steroids

Disqualifiers: Active infections, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

13 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Purpose of this Pilot Study: The investigators want to study the safety, side effects, and benefits of tumor infiltrating lymphocytes (TILs), when they are given with the drug ipilimumab. Ipilimumab is a type of immunotherapy - a drug that is used to boost the ability of the immune system to fight cancer, infection, and other diseases.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic immunosuppressive steroids or medications for autoimmune diseases, you may not be eligible to participate.

What safety data exists for ipilimumab in treating melanoma?

Ipilimumab, used for treating melanoma, can cause immune-related side effects like skin rashes, liver issues, and inflammation of the gut, which are usually manageable but can sometimes be serious. Close monitoring and proper management can help control these side effects, allowing patients to benefit from the treatment. ^{1 2 3 4 5}

How is the treatment with Adoptive Cell Therapy and Ipilimumab for melanoma different from other treatments?

This treatment is unique because it combines adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) with Ipilimumab, aiming to enhance the immune system's ability to fight melanoma. TIL therapy has shown promising results, especially in patients with advanced melanoma who have not responded to other treatments, offering a potential for long-term remission. ^{6 7 8 9 10}

What data supports the effectiveness of this treatment for melanoma?

Research shows that adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) combined with high-dose interleukin-2 (IL-2) has a response rate of about 40%-50% in patients with advanced melanoma, with some patients experiencing long-lasting remission. This suggests that the treatment can be effective, especially for those who have not responded to other therapies. ^{6 7 8 10 11}

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 stage III or IV melanoma that hasn't spread to more than three areas in the brain. They can't have had ipilimumab before but may have had other treatments. Participants need good organ function and performance status, not be pregnant, agree to use contraception, and cannot have certain medical conditions or a history of severe autoimmune disease.

Inclusion Criteria

I do not have serious heart rhythm problems.

All laboratory and imaging studies must be completed and satisfactory within 30 days of signing the consent document, with specific exceptions

My tumor may have a BRAF mutation, and I haven't been treated with ipilimumab.

Exclusion Criteria

My brain scans show no growth in my cancer 90 days after treatment for more than 3 or larger than 1 cm brain tumors.

I am taking immunosuppressive drugs for an autoimmune disease.

I am unable to understand and agree to the study's details.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Long-term Follow-up

Participants are monitored for progression-free survival

42 months

What Are the Treatments Tested in This Trial?

Interventions

• Administration of Lymphodepletion
• Adoptive Cell Therapy with TIL
• Cyclophosphamide as Part of Lymphodepletion
• Fludarabine as Part of Lymphodepletion
• High Dose IL-2
• Ipilimumab

Trial Overview The study tests combining TIL (a type of white blood cell) therapy with ipilimumab (an immunotherapy drug), along with lymphodepletion (lowering white blood cells), high dose IL-2 (a substance that activates immune cells), and adoptive cell transfer to see if this approach is safe and effective against melanoma.

How Is the Trial Designed?

Group I: Combination Therapy Experimental Treatment 7 Interventions

The combination of ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials

26

Recruited

1,800+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Ipilimumab, an antibody that enhances T-cell activation, is effective for treating metastatic melanoma but can cause immune-mediated side effects, including rare cases of ileitis without colitis, as seen in a 54-year-old patient.

The study highlights the need for further research into genetic and epigenetic factors to personalize treatment and minimize adverse effects associated with ipilimumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis. Venditti, O., De Lisi, D., Caricato, M., et al.[2018]

Ipilimumab, an anti-CTLA-4 monoclonal antibody, significantly extends overall survival in patients with unresectable stage III or IV melanoma by enhancing T-cell activation and immune response against tumors.

While ipilimumab can lead to immune-related adverse events (irAEs), which are often manageable, proper management strategies are crucial to ensure patients can safely benefit from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-mediated adverse events associated with ipilimumab ctla-4 blockade therapy: the underlying mechanisms and clinical management. Tarhini, A.[2022]

Ipilimumab, a monoclonal antibody targeting CTLA-4, has been shown to significantly improve overall survival in patients with metastatic melanoma, with a median survival of 10.1 months compared to 6.4 months for those receiving a vaccine alone in a phase III trial involving previously treated patients.

While ipilimumab offers a clear survival benefit, it is associated with serious immune-related adverse events in 10% to 15% of patients, necessitating careful monitoring and potential use of immune-suppressive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma. Lipson, EJ., Drake, CG.[2022]

In a study of 56 patients with metastatic melanoma who had severe immune-related adverse events (AEs) from ipilimumab, 36% experienced at least one immune-related AE after receiving anti-PD-1 therapy, indicating a notable risk of recurrence but also a manageable safety profile.

Despite the risk of AEs, anti-PD-1 therapy showed a 43% overall response rate and a median overall survival of 21 months, suggesting it may offer improved outcomes for patients previously affected by severe toxic effects from ipilimumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Anti-Programmed Cell Death 1 Antibody Treatment With Risk of Recurrence of Toxic Effects After Immune-Related Adverse Events of Ipilimumab in Patients With Metastatic Melanoma. Brunot, A., Grob, JJ., Jeudy, G., et al.[2021]

In a phase II clinical trial involving 31 patients with metastatic melanoma, adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) resulted in a 48.4% objective clinical response rate, with 6.5% of patients achieving complete remission.

The study found that a higher number of infused TIL, particularly those with a greater proportion of CD8(+) T cells and a more differentiated effector phenotype, were significantly associated with better tumor regression outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Radvanyi, LG., Bernatchez, C., Zhang, M., et al.[2022]

Citations

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

Adoptive Cellular Therapy for Metastatic Melanoma: The Road to Commercialization and Treatment Guidelines for Clinicians. [2022]

2. 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]

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

Genomic Correlates of Outcome in Tumor-Infiltrating Lymphocyte Therapy for Metastatic Melanoma. [2022]

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

Tumor-Infiltrating Lymphocytes: Clinical Experience. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Minimally invasive liver resection to obtain tumor-infiltrating lymphocytes for adoptive cell therapy in patients with metastatic melanoma. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis. [2018]

7. Egypt pubmed.ncbi.nlm.nih.gov

Immune-mediated adverse events associated with ipilimumab ctla-4 blockade therapy: the underlying mechanisms and clinical management. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Elevated rates of transaminitis during ipilimumab therapy for metastatic melanoma. [2017]

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

Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma. [2022]

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

Association of Anti-Programmed Cell Death 1 Antibody Treatment With Risk of Recurrence of Toxic Effects After Immune-Related Adverse Events of Ipilimumab in Patients With Metastatic Melanoma. [2021]

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

Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. [2022]