Cell Therapy for Metastatic Melanoma Using CD8 Enriched Tumor Infiltrating Lymphocytes

• Status: Terminated
• Trial end date: 2015-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• One experimental treatment for certain types of cancer is cell therapy, which involves collecting lymphocytes (white blood cells) from a tumor, growing them in the laboratory in large numbers, and then modifying the cells with a gene (interleukin-12 (IL-12)) that stimulates the immune system to attack and destroy the cancer cells. Because this treatment is experimental, researchers are interested in determining the side effects and overall effectiveness of cell therapy using white blood cells modified with IL-12 as a treatment for aggressive cancer.

Objectives:

• To determine the safety and effectiveness of cell therapy using IL-12 modified tumor white blood cells to treat metastatic melanoma.

Eligibility:

• Individuals greater than or equal to 18 years of age and less than or equal to age 66 who have been diagnosed with metastatic melanoma.

Design:

• Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies.

• Cells for treatment will be collected during tumor biopsy or surgery.

• Prior to the start of cell therapy, participants will have imaging procedures, heart and lung function tests, and blood and urine tests, as well as leukapheresis to collect additional white blood cells.

• For 5 days before the cell infusion, participants will be admitted for inpatient chemotherapy with cyclophosphamide and fludarabine to suppress the immune system in preparation for the cell therapy.

• Participants will receive the modified white blood cells as an infusion 1 to 4 days after the last dose of chemotherapy. The day after the infusion, participants will receive filgrastim to stimulate blood cell growth.

• Participants will remain as inpatients for at least 5 to 10 days to recover from the treatment, and will be followed regularly after the treatment to study side effects and general effectiveness.

• Participants who initially respond to treatment but have a relapse may have one additional treatment using the same procedure.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-12; Vidarabine

Criteria

• INCLUSION CRITERIA:

• Metastatic melanoma with evaluable disease.

• Greater than or equal to 18 years of age and less than or equal to age 66.

• Willing to sign a durable power of attorney

• Able to understand and sign the Informed Consent Document

• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1

• Life expectancy of greater than three months

• Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after the cells are no longer detected in the blood.

• Serology:

• Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)

• Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by reverse transcription polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative.

• Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.

• Hematology:

• Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.

• White blood cell (WBC) (> 3000/mm^3).

• Platelet count greater than 100,000/mm^3.

• Hemoglobin greater than 8.0 g/dl.

• Chemistry:

• Serum alanine transaminase (ALT)/aspartate transaminase (AST) less or equal to 2.5 times the upper limit of normal.

• Serum creatinine less than or equal to 1.6 mg/dl.

• Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilberts Syndrome who must have a total bilirubin less than 3.0 mg/dl.

• More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).

EXCLUSION CRITERIA:

• Previous treatment with interleukin-12 (IL-12).

• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

• Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.

• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).

• Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).

• Concurrent systemic steroid therapy.

• History of severe immediate hypersensitivity reaction to any of the agents used in this study.

• In patients > 60 years old and/or history of coronary revasularization or ischemic symptoms, documented left ventricular ejection fraction (LVEF) of less than or equal to 45%.