36 Participants Needed

CD40L-augmented TIL for Melanoma

KS
TS
Overseen ByTina Swartzlander
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CD40L-augmented TIL, a type of cell therapy, for individuals with advanced melanoma, a type of skin cancer. The researchers aim to determine if this treatment is safe and effective for patients whose cancer hasn't responded to standard therapies. Participants will have a tumor removed to prepare the treatment and will receive additional medications to aid the process. This trial suits those with advanced melanoma that has not improved with usual treatments. 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.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications, such as systemic steroid therapy above a low dose, at least one week before starting the trial. If you are on immunosuppressive medications or high-dose steroids, you may need to taper off before participating.

Is there any evidence suggesting that CD40L-augmented TIL is likely to be safe for humans?

Research shows that Tumor-Infiltrating Lymphocyte (TIL) therapy has received FDA approval for treating melanoma, indicating its safety for this condition is well-understood. Studies are ongoing to test a new version called CD40L-augmented TIL, focusing on its safety.

Early results from other studies examine how well patients tolerate CD40L-augmented TIL, assessing how patients handle the treatment. Researchers closely monitor safety, especially after every four patients, to detect any harmful effects early.

While detailed safety information for CD40L-augmented TIL is still being collected, its similarity to the approved TIL therapy suggests it might be safe for treating melanoma. However, this treatment remains experimental, and further research is needed to confirm its safety.12345

Why are researchers excited about this study treatment for melanoma?

Researchers are excited about CD40L-augmented TIL for melanoma because it introduces a novel approach to cancer treatment by enhancing the activity of tumor-infiltrating lymphocytes (TILs) with the CD40 ligand (CD40L). Most traditional treatments for melanoma, like immune checkpoint inhibitors and targeted therapies, focus on blocking cancer growth or boosting the immune response in a broader way. However, CD40L-augmented TIL specifically supercharges the immune cells already present in the tumor, potentially increasing their ability to attack cancer cells more effectively. This targeted enhancement could lead to better outcomes, especially for patients with rare melanoma subtypes, where existing treatments are limited.

What evidence suggests that CD40L-augmented TIL might be an effective treatment for melanoma?

Research has shown that a new treatment using enhanced immune cells, called CD40L-augmented tumor-infiltrating lymphocytes (TIL), may help treat advanced melanoma. CD40L activates immune cells like B-cells, potentially boosting the body's ability to fight cancer. This trial will evaluate CD40L-augmented TIL in different cohorts, including a Phase I safety trial, a Phase II efficacy trial, and a cohort for rare melanoma subtypes. Early results suggest these modified TILs could help melanoma patients who haven't responded to other treatments. While more clinical data is needed, this therapy offers a promising new way to address melanoma.12678

Who Is on the Research Team?

LK

Lilit Karapetyan, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with advanced melanoma, specifically cutaneous acral and non-acral melanoma (26 people), as well as mucosal and uveal melanoma (10 people). Participants must have progressive disease after standard treatments. They will undergo tumor removal for TIL preparation and must be fit for lymphodepletion.

Inclusion Criteria

Participants must be seronegative for HIV, hepatitis B, and hepatitis C
Participants must be willing to sign an informed consent document
My melanoma is advanced and cannot be removed by surgery.
See 7 more

Exclusion Criteria

Participants with primary or acquired immunodeficiency disorders
Pregnant or breastfeeding women
Participants with severe hypersensitivity reactions to study agents
See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Tumor Excision

Patients undergo an excision of a readily accessible tumor for preparation of TIL

1 week

Lymphodepletion

Eligible patients undergo lymphodepletion with cyclophosphamide and fludarabine

1 week

Treatment

Patients receive a single dose of CD40L-augmented TIL followed by standard of care bolus dose interleukin-2

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Participants are monitored for long-term outcomes such as overall survival and progression-free survival

Up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

  • CD40L-augmented TIL
Trial Overview The study tests a single dose of CD40L-augmented TIL in two cohorts of melanoma patients. It involves removing a tumor to prepare the TIL, then treating patients with cyclophosphamide and fludarabine to weaken their immune system before administering the TIL followed by interleukin-2.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Group I: Cohort 2: Rare melanoma subtypesExperimental Treatment4 Interventions
Group II: Cohort 1: Phase II efficacy trialExperimental Treatment4 Interventions
Group III: Cohort 1: Phase I safety trialExperimental Treatment4 Interventions

Find a Clinic Near You

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

CD40 agonists have shown potential in cancer immunotherapy, demonstrating moderate antitumor effects in some tumors, based on early clinical trials.
The adverse events associated with CD40 agonists, such as cytokine release and hepatotoxicity, have been mostly transient and manageable, suggesting a favorable safety profile for further investigation.
Characteristics and clinical trial results of agonistic anti-CD40 antibodies in the treatment of malignancies.Li, DK., Wang, W.[2020]

Citations

NCT06961357 | Clinical Trial of CD40L-augmented TIL for ...This is a phase I/II clinical trial of a single dose of CD40L-augmented TIL administered in patients with advanced melanoma (Cohort 1: Cutaneous acral ...
Tumor-Infiltrating Lymphocyte Therapy: A New FrontierThe goal of knocking out PDCD-1 in TILs is to enhance TIL efficacy and potentially avoid the need for systemic anti-PD-1 therapy and its associated toxicities.
CD40L stimulates tumor-infiltrating B-cells and improves ex ...We now report the results obtained in human melanoma and lung TIL of CD40L-enhanced TIL expansion and quality and provide mechanistic insight ...
Clinical Trials Using CD40L-augmented Autologous Tumor ...Review the clinical trials studying cd40l-augmented autologous tumor infiltrating lymphocytes on this list and use the filters to refine the results by age ...
Research Creates Hope and Hope Changes EverythingDr. Karapetyan's project is timely as the first cancer tumor infiltrating lymphocyte (TIL) therapy (AMTAGVI™) was recently approved by the FDA ...
Lymphodepletion Chemotherapy, CD40L-Augmented ...To evaluate the safety and toxicity of CD40L-augmented TIL administered in patients with advanced melanoma. II. To evaluate the efficacy of CD40L-augmented ...
Melanoma Clinical TrialsPhase I/II Clinical Trial of CD40L-augmented Tumor Infiltrating Lymphocytes (TIL) for Patients with Advanced Melanoma Condition: Cutaneous Intervention ...
Top Uveal Melanoma Clinical Trials | PowerThis is a phase I/II clinical trial of a single dose of CD40L-augmented TIL administered in patients with advanced melanoma (Cohort 1: Cutaneous acral melanoma, ...
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