What side effects are associated with this type of intervention?

Common treatments for melanoma include immune cell therapies and alkylating agents like Temozolomide. Immune cell therapies, such as those involving natural killer (NK) cells, can cause side effects like inflammation in various organs, including the skin, liver, and gastrointestinal tract. These therapies may also lead to autoimmune reactions and hematologic toxicities. Temozolomide, an alkylating agent, is known to cause side effects such as nausea, vomiting, fatigue, and myelosuppression, which can lead to anemia, leukopenia, and thrombocytopenia. Both treatment types aim to enhance anti-tumor immunity and inhibit cancer cell growth, respectively.

What prior FDA approvals exist?

The FDA has approved several treatments for melanoma that enhance anti-tumor immunity and use alkylating agents. Immune checkpoint inhibitors like nivolumab and ipilimumab have been approved for their ability to boost the immune system's response against melanoma cells. Pembrolizumab, another checkpoint inhibitor, is also approved for melanoma treatment. Temozolomide, an alkylating agent, is used to slow or stop the growth of cancer cells, particularly in cases where melanoma has metastasized to the brain. These treatments align with the mechanisms of action being studied in the trial involving UD TGFbetai NK cells and Temozolomide.

What other types of research exist?

Promising novel alternatives for melanoma treatment in 2024 include: 1) Nivolumab (PD-1 inhibitor) and Ipilimumab (CTLA-4 inhibitor) combination therapy, which has shown improved response rates in advanced melanoma. 2) Pembrolizumab (PD-1 inhibitor), effective in high-risk node-positive melanoma. 3) Dabrafenib plus Trametinib (BRAF and MEK inhibitors), suitable for patients with BRAF V600 mutations who prefer oral targeted therapy.

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CAR T-cell Therapy

NK Cell Therapy + Temozolomide for Melanoma with Brain Metastasis

Phase 1 & 2

Recruiting

Led By Kari L Kendra, MD

Research Sponsored by Kari Kendra

Eligibility Criteria Checklist

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

Must have

No indication for stereotactic radiotherapy

Radiologically confirmed brain metastasis (n >= 1) with at least one measurable central nervous system (CNS) lesion >= 10 mm on T1-weighted gadolinium enhanced magnetic resonance imaging (MRI) and unequivocal evidence of progression

Must not have

Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as: Active infection, Current active hepatic or renal disease

Planned or concurrent systemic treatment or radiation therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of special immune cells and a cancer drug to treat patients with advanced melanoma that has spread to the brain. The immune cells aim to kill the cancer, and the drug helps stop its growth. A new treatment has shown effectiveness against advanced melanoma and brain involvement.

Who is the study for?

This trial is for adults over 18 with stage IV melanoma that has spread to the brain. Participants must have finished any cancer treatments at least 4 weeks prior, have certain normal organ function tests, and no severe mental status changes or other serious medical conditions. Women of childbearing age and men who can father a child must use effective contraception.

What is being tested?

The trial is testing the safety and effectiveness of UD TGFbetai NK cell therapy combined with temozolomide in shrinking brain tumors caused by melanoma. It's exploring the best dose of these therapies in patients whose cancer has advanced despite previous treatments.

What are the potential side effects?

Potential side effects may include reactions from the immune system due to NK cell therapy, as well as typical chemotherapy-related issues like fatigue, nausea, hair loss, and increased risk of infections from temozolomide.

Eligibility Criteria

Inclusion Criteria

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

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I am not a candidate for precise, high-dose radiation therapy.

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I have at least one brain tumor larger than 10 mm that is growing.

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My melanoma is confirmed and has spread to other parts of my body.

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I can take care of myself and am up and about more than half of the day.

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I am older than 18 years.

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

Exclusion Criteria

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

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I do not have any severe illnesses like active infections or liver/kidney diseases.

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I am scheduled for or currently receiving chemotherapy or radiation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 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

Dose limited toxicities (Phase I)

Incidence of adverse events (AEs) (Phase I)

Proportion of subjects who achieve an intracranial complete response or partial response (Phase II)

Secondary study objectives

Extracranial response rate (Phase II)

Temozolomide

Overall Survival (OS) (Phase II)

+2 more

Other study objectives

Cerebrospinal fluid shunts procedure

Immune activation post infusion

Natural Killer Cells

+1 more

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 (UD TGFbetai NK cells, temozolomide)Experimental Treatment2 Interventions

Patients receive UD TGFbetai NK cells IV over 30 minutes on day 1 and temozolomide PO daily on days 1-5. Treatment with UD TGFbetai NK cells repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Cycles of temozolomide repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Natural Killer Cell Therapy

2013

Completed Phase 2

~180

Temozolomide

2010

Completed Phase 3

~1880

0 / 8Eligibility 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

Melanoma treatments often include immune cell therapies and alkylating agents. Immune cell therapies, such as the use of natural killer (NK) cells, enhance the body's immune response by recognizing and destroying cancer cells, thereby boosting anti-tumor immunity. This is crucial for melanoma patients as it leverages the body's natural defenses to target and eliminate cancer cells. Alkylating agents like Temozolomide work by adding alkyl groups to DNA, which interferes with the DNA replication process, ultimately slowing or stopping the growth of cancer cells. This dual approach of enhancing immune response and directly targeting cancer cell replication is vital for effectively managing melanoma, especially in advanced stages.