What side effects are associated with this type of intervention?

Common treatments for melanoma, particularly those involving genetically modified T cells like IL13Ralpha2 CAR T cells, can have several side effects. These include cytokine release syndrome (CRS), which may cause fever, fatigue, and muscle pain, as well as neurotoxicity, leading to confusion, headaches, or seizures. Other potential side effects are infusion reactions, low blood cell counts, and an increased risk of infections due to immune system modulation.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of melanoma, particularly those involving genetically modified T cells. One notable example is the approval of T-cell receptor (TCR) gene therapy targeting specific cancer antigens. Additionally, chimeric antigen receptor (CAR) T-cell therapies, although more commonly associated with hematologic malignancies, are being explored for solid tumors like melanoma. These therapies involve modifying a patient's T cells to express receptors that target tumor-specific proteins, similar to the IL13Ralpha2 CAR T cells being studied. Other approved immunotherapies for melanoma include checkpoint inhibitors like nivolumab and ipilimumab, which enhance the immune system's ability to attack cancer cells.

What other types of research exist?

Promising novel alternatives to IL13Ralpha2 CAR T cells for melanoma patients include: 1) Immune checkpoint inhibitors such as pembrolizumab (anti-PD-1) and nivolumab (anti-PD-1), which have shown significant efficacy in melanoma. 2) Combination therapies involving checkpoint inhibitors and other agents like ipilimumab (anti-CTLA-4) combined with nivolumab. 3) Adoptive cell transfer therapies, including tumor-infiltrating lymphocytes (TILs) therapy. 4) Bispecific antibodies targeting multiple tumor antigens. 5) Personalized cancer vaccines targeting specific neoantigens identified in the patient's tumor. These alternatives offer diverse mechanisms to enhance the immune response against melanoma.

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CAR T-cell Therapy

IL13Ralpha2 CAR T Cells for Advanced Skin Cancer

Phase 1

Recruiting

Led By Antoni Ribas

Research Sponsored by Jonsson Comprehensive Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Must have received at least one prior systemic therapy for advanced melanoma (i.e. anti-PD-1 therapy, BRAF plus MEK inhibitor therapy for BRAFV600 mutated melanoma) and is not considered to have an alternate treatment option with curative intent

A minimum of one measurable lesion defined as meeting the criteria for measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) or skin lesion(s) selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s)

Must not have

A Tiffeneau-Pinelli index < 70% of the predicted value. Subjects will be excluded if pulmonary function tests indicate they have insufficient pulmonary capability

Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT (QTC) > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus tachycardia (HR>120 beats per minute) will be evaluated by a cardiologist prior to starting the trial. Patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as > 20 premature ventricular complex [PVC]s per minute), ventricular tachycardia, 3rd degree heart block will be excluded from the study unless cleared by a cardiologist

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety and best dose of modified immune cells for patients with advanced melanoma or other cancers that have spread. The treatment uses the patient's own T cells, which are changed in a lab to better attack cancer cells. The goal is to see if these modified cells can safely and effectively fight the cancer.

Who is the study for?

This trial is for adults with advanced melanoma (Stage IIIC or IV) who have tried at least one other treatment and can't be cured by surgery. They must have a certain protein on their cancer cells, be in good physical shape, and able to undergo a procedure to collect immune cells. Pregnant women, those with heart issues, severe allergies to study drugs, active infections like HIV or hepatitis B/C, or using immunosuppressive drugs can't join.

What is being tested?

The trial tests genetically modified immune cells called IL13Ralpha2 CAR T Cells after chemotherapy (cyclophosphamide and fludarabine phosphate) plus interleukin-2. It aims to find the safest dose of these modified cells that stay in the body and effectively target melanoma.

What are the potential side effects?

Possible side effects include reactions from the infusion of modified T-cells, effects from chemotherapy such as nausea and hair loss, increased risk of infection due to weakened immunity from conditioning treatments, fatigue, fever, and potential organ inflammation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I've had treatment for advanced melanoma but no curative options are left.

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I have at least one tumor that can be measured accurately.

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My tumor shows IL13Ralpha2 expression.

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I am fully active or can carry out light work.

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My melanoma cannot be removed by surgery and is either stage IIIC or IV.

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I am willing to undergo a procedure to collect white blood cells.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My lung function is below 70% of what is expected.

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My heart test results are normal or cleared by a cardiologist.

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I do not have another active cancer that could affect this study's results.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events

Secondary study objectives

Objective response rate

Other study objectives

Evaluation of an endogenous T cell anti-tumor response

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (chemotherapy, IL13Ralpha2)Experimental Treatment9 Interventions

Patients may receive cyclophosphamide IV over 60 minutes on days -5 to -3 and fludarabine phosphate IV over 15-30 minutes on days -5 to -2. Patients then receive IL13Ralpha2 CAR T cells IV on day 0. Patients also undergo biopsy at baseline and on study, CT, or PET and CT scan at screening and on study, magnetic resonance imaging (MRI) throughout the trial, and collection of blood samples throughout the trial. Patients with disease progression may receive a second cycle with an infusion of IL13Ralpha2 CAR T cells.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Positron Emission Tomography

2011

Completed Phase 2

~2200

Biospecimen Collection

2004

Completed Phase 3

~2020

Computed Tomography

2017

Completed Phase 2

~2740

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Biopsy

2014

Completed Phase 4

~1090

Cyclophosphamide

2010

Completed Phase 4

~2310

Fludarabine Phosphate

1997

Completed Phase 3

~2390

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for melanoma, particularly advanced stages, include immunotherapies such as checkpoint inhibitors and CAR T cell therapies. Checkpoint inhibitors like nivolumab and ipilimumab work by blocking proteins (PD-1 and CTLA-4) that prevent T cells from attacking cancer cells, thereby enhancing the immune response against tumors. CAR T cell therapies, such as those targeting IL13Ralpha2, involve modifying a patient's T cells to express receptors that specifically bind to proteins on melanoma cells, leading to targeted tumor cell destruction. These treatments are crucial for melanoma patients as they offer targeted, potent options that can lead to significant tumor reduction and potentially prolonged survival, especially in cases where traditional therapies have failed.