Use of IL-15 After Chemotherapy and Lymphocyte Transfer in Metastatic Melanoma

• Status: Terminated
• Trial end date: 2014-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Researchers have developed an experimental cancer treatment called cell therapy. White blood cells called lymphocytes are taken from a tumor, grown in large numbers in the lab, and then given back to the patient. Interleukin-15, given to the patient after the cells (now called Young tumor-infiltrating lymphocytes of Young TIL cells) are replaced, helps the cells to grow and boosts the immune system. This process changes your normal cells into cells that are able to recognize your tumor has been studied in the lab. These cells can destroy tumor cells in the test tube, but scientists want to see if they work inside the body.

Objectives:

-To test the effectiveness of lymphocytes drawn from tumor cells combined with interleukin-15 in treating metastatic melanoma.

Eligibility:

• Patients must be 18 - 66 years of age and have a diagnosis of metastatic melanoma.

• They will have heart and lung function tests, lab tests, and imaging procedures.

• Patients may not have conditions such as active systemic infections, blood clotting disorders, or other active major medical illnesses.

• Patients may not be pregnant or nursing.

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

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Cyclophosphamide; Fludarabine; Polystyrene sulfonic acid

Criteria

• INCLUSION CRITERIA:

1. Measurable metastatic melanoma with available autologous tumor infiltrating lymphocyte (TIL).

2. Patients with 3 or less brain metastases are eligible. Note: If lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been treated and stable for 3 months for the patient to be eligible.

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

4. Able to understand and sign the Informed Consent Document

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

6. Life expectancy of greater than three months.

7. 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 receiving the preparative regimen.

8. Serology:

1. 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.)

2. 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.

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

9. Hematology:

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

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

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

4. Hemoglobin greater than 8.0 g/dl.

10. Chemistry:

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

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

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

11. 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).

Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria.

12. Six weeks must have elapsed from the time of any antibody therapy that could affect an anti cancer immune response, including anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody therapy, at the time the patient receives the preparative regimen to allow antibody levels to decline.

13. Patients who have previously received any anti-CTLA4 antibody and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.

EXCLUSION CRITERIA:

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

2. 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.

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

4. 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).

5. Concurrent systemic steroid therapy.

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

7. Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.

8. In patients > 60 years old, documented LVEF of less than or equal to 45%.

9. Documented LVEF of less than or equal to 45% tested in patients with:

1. clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or.

2. age greater than or equal to 60 years old.

10. Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with:

1. A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).

2. Symptoms of respiratory dysfunction.