Cell Therapy + Chemo + TBI for Skin Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Systemic steroids

Disqualifiers: Pregnancy, Infections, Immunodeficiency, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

102 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: - An experimental treatment for metastatic melanoma involves cell therapy, in which researchers take white blood cells (lymphocytes) from the tumor tissue, grow them in the laboratory in large numbers, and then use the cells to attack the tumor tissue. Before receiving the cells, chemotherapy is needed to temporarily suppress the immune system to improve the chances that the tumor-fighting cells will be able to survive in the body. In some studies of cell therapy, individuals who have received total body irradiation (TBI) in addition to the chemotherapy (in order to increase the length of time that they do not produce white blood cells) seem to have a slightly better response to the treatment, but it is not known if adding radiation to the cell therapy will cause a better response for all individuals. Researchers are interested in comparing cell therapy given with the usual chemotherapy to cell therapy given with the usual chemotherapy and TBI. Objectives: - To compare the effectiveness of cell therapy given with chemotherapy to cell therapy given with chemotherapy and total body irradiation in individuals with metastatic melanoma. Eligibility: - Individuals at least 18 years of age who have been diagnosed with metastatic melanoma. Design: * Participants will be screened with a physical examination, medical history, blood tests, and tumor imaging studies. * Participants will be divided into two groups: cell therapy with chemotherapy alone (group 1) or cell therapy with chemotherapy plus TBI (group 2). * All participants will provide a tumor sample from either surgery or a tumor biopsy for white blood cell collection. * Participants will have leukapheresis to collect additional white blood cells for cell growth and future testing, and TBI group participants will also provide stem cells to help them recover after radiation. (TBI participants who cannot provide enough stem cells will be moved to the non-radiation treatment group.) * Participants will have chemotherapy with cyclophosphamide (two treatments over 2 days) and fludarabine (five treatments over 5 days) starting 7 days before the cell therapy. Participants in the TBI group will also have TBI for the 3 days immediately before the cell therapy. * All participants will receive the white blood cells, followed by high-dose aldesleukin every 8 hours for up to 5 days after the cell infusion to help keep the therapy cells alive and active. Participants will also have injections of filgrastim to stimulate blood cell production, and participants in the TBI group will also receive their stem cells. * Participants will take an antibiotic for at least 6 months after treatment to prevent pneumonia, and will be asked to return for regular monitoring and followup visits for at least 5 years to evaluate the tumor s response to treatment.

Research Team

Steven A Rosenberg, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults aged 18-66 with metastatic melanoma, able to consent, and have a life expectancy over three months. They must be in good health otherwise, not HIV or hepatitis positive, and have a tumor suitable for cell extraction. Women can't be pregnant/breastfeeding; participants must use birth control during/after the trial.

Inclusion Criteria

You are expected to live for more than three months.

Willing to sign a durable power of attorney.

Able to understand and sign the Informed Consent Document

Exclusion Criteria

My immune system is strong and I don't have infections that occur more often or are more severe because of weakened immunity.

I have undergone cell transfer therapy with intense chemotherapy.

I do not have any active major illnesses or infections affecting my heart, lungs, or immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Chemotherapy

Participants receive a non-myeloablative lymphodepleting chemotherapy regimen with cyclophosphamide and fludarabine over 7 days before cell therapy

7 days

Daily visits for chemotherapy administration

Cell Therapy and IL-2 Administration

Participants receive tumor-infiltrating lymphocytes followed by high-dose aldesleukin every 8 hours for up to 5 days

5 days

Multiple visits for IL-2 administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with regular follow-up visits for at least 5 years

5 years

Regular visits every 3 months for the first year, then every 6 months

Treatment Details

Interventions

• Aldesleukin
• Cyclophosphamide
• Fludarabine
• Total Body Irradiation (TBI)
• Young TIL
• Young Tumor Infiltrating Lymphocytes

Trial Overview The study is testing if adding total body irradiation (TBI) to chemotherapy before cell therapy improves outcomes in metastatic melanoma patients. Participants are split into two groups: one receives just chemo while the other gets chemo plus TBI before their own grown white blood cells are reintroduced.

Participant Groups

Group I: 2/ACT + TBI Experimental Treatment 5 Interventions

Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young TIL + highdose aldesleukin + TBI

Group II: 1/ACT Experimental Treatment 4 Interventions

Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young TIL + highdose aldesleukin

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+