Phase II Study of Short-Term Cultured Anti-Tumor Autologous Lymphocytes After Lymphocyte-Depleting Chemotherapy in Metastatic Melanoma

• Status: Completed
• Trial end date: 2012-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Most therapeutic therapies for metastatic melanoma have focused on the ability of T-cell lymphocytes to kill cells of tumors.

• An adaptive cell transfer therapy has been pioneered, in which cells are grown for a short time in the laboratory. The way they are grown may have a better effect in a patient's body than do other cells that are cultured for a longer time.

Objectives:

• To determine whether tumor-infiltrating lymphocytes (TIL) can be put in cells removed from patients' tumors or blood and then reinfused, with the purpose of shrinking tumors.

• To evaluate safety and effectiveness of the treatment.

Eligibility:

• Patients 18 years of age or older with metastatic cancer melanoma (cancer that has spread beyond the original site).

• Patient's leukocyte antigen type is human leukocyte antigens (HLA-A) 0201.

Design:

-Patients undergo the following procedures:

• Leukapheresis (on two occasions). This is a method of collecting large numbers of white blood cells. The cells obtained in the first leukapheresis procedure are grown in the laboratory, and the TIL cells (called young TIL cells) are inserted into the cells using an inactivated (harmless) virus in a process called retroviral transduction. Cells collected in the second leukapheresis procedure are used to evaluate the effectiveness of the study treatment.

• Chemotherapy. Patients are given chemotherapy through a vein (intravenously, IV) over 1 hour for 2 days to suppress the immune system so that the patient's immune cells do not interfere with the treatment.

• Treatment with young TIL cells. Patients receive an IV infusion of the treated cells, followed by infusions the drug aldesleukin-2 (IL-2), which helps boost the effectiveness of the treated white cells.

• Patients are given support medications to prevent complications such as infections.

• Patients may undergo a tumor biopsy (removal of a small piece of tumor tissue).

• Patients are evaluated with laboratory tests and imaging tests, such as computed tomography (CT) scans, 4 to 6 weeks after treatment and then once a month for 3 to 4 months to determine the response to treatment.

• Patients have blood tests at 3, 6, and 12 months and then annually for 5 years.

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

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2

Criteria

-INCLUSION CRITERIA:

1. Measurable metastatic melanoma with at least one lesion that is resectable for tumor infiltrating lymphocytes (TIL) generation.

2. Patients with one to three brain metastases are eligible (lesions greater than or equal to 1 cm each, or symptomatic lesions must have been treated and stable for 3 months).

3. Greater than or equal to 18 years of age .

4. Willing to practice birth control during treatment and for four months after receiving the preparative regimen.

5. Life expectancy of greater than three months.

6. Willing to sign a durable power of attorney.

7. Able to understand and sign the Informed Consent Document.

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

9. Hematology:

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

• Normal white blood cell (WBC) (greater than 3000/ mm^3).

• Hemoglobin greater than 8.0 g/dl.

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

10. 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 or hepatitis C.

11. Chemistry: . Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than three times the upper limit of normal. Serum creatinine less than or equal to 1.6 mg/dl. Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl.

12. 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). Patients may have undergone minor surgical procedures with the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria in Section 2.1.1.

13. Six weeks must have elapsed since prior MDX-010 (Ipilimumab) therapy to allow antibody levels to decline.

14. Patients who have previously received any anti-CTLA4 (cytotoxic T-lymphocyte antigen 4) antibody and experienced treatment related colitis must have a normal colonoscopy with normal colonic biopsies.

EXCLUSION CRITERIA:

1. Prior cell transfer therapy that included non-myeloablative or ablative chemotherapy (for cohorts 4 and 5).

2. 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.

3. Systemic steroid therapy required.

4. Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.

5. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and Acquired Immune Deficiency Syndrome (AIDS)).

6. 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.)

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

8. History of coronary revascularization or ischemic symptoms.

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

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

• Clinically significant atrial and/or ventricular arrhythmias including but not limited to:

atrial fibrillation, ventricular tachycardia, second or third degree heart block.

• Age greater than or equal to 60 years old.

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

• A prolonged history of cigarette smoking

• Symptoms of respiratory dysfunction