A Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Short-Term Cultured Tumor-Infiltrating Lymphocytes Plus IL-2 Following Either a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI)
A Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Short-Term Cultured Tumor-Infiltrating Lymphocytes Plus IL-2 Following Either a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI)
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:
Background:
Objectives:
-To determine, in a prospective randomized trial, the complete response rate and survival of patients with metastatic melanoma receiving adoptive cell transfer (ACT) using young TIL plus aldesleukin treatment following either a chemotherapy preparative regimen alone, or the same chemotherapy preparative regimen plus TBI.
Eligibility:
-Patients who are 18 years or older must have:
Design:
-Patients with metastatic melanoma will have lesions resected and after TIL growth is established patients with will be prospectively randomized to receive ACT with young TIL plus aldesleukin following either a non-myeloablative chemotherapy preparative regimen or this same regimen plus TBI.
INCLUSION CRITERIA:
Absolute neutrophil count greater than 1000/mm(3)
Hemoglobin greater than 8.0 g/dl
Platelet count greater than 100,000/mm(3)
j. 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, or hepatitis C antibody or antigen.
k. Chemistry:
Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than three times the upper limit of normal.
Calculated creatinine clearance (eGFR) > 50 ml/min.
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.
l. More than four weeks must have elapsed since any prior systemic therapy at the time of randomization, and patient's toxicities must have recovered to a grade 1 or less (except for alopecia or vitiligo). Patients must have stable or progressing disease after prior treatment.
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 inclusion criteria.
m. Six weeks must have elapsed since any prior anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) antibody therapy to allow antibody levels to decline.
Note: Patients who have previously received ipilimumab or tremelimumab, anti-programmed cell death protein 1 (PD1) or anti-programmed cell death ligand 1 (PD-L1) antibodies and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.
EXCLUSION CRITERIA:
Prior cell transfer therapy which included a non-myeloablative or myeloablative chemotherapy regimen.
Women of child-bearing potential who are pregnant or breastfeeding because 10 of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
Systemic steroid therapy requirement.
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.
Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and acquired immunodeficiency syndrome (AIDS).
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.)
History of severe immediate hypersensitivity reaction to any of the agents used in this study.
History of coronary revascularization or ischemic symptoms.
Any patient known to have a left ventricular ejection fraction (LVEF) less than or equal to 45%.
In patients > 60 years old, documented LVEF of less than or equal to 45%.
Documented forced expiratory volume in one second (FEV1) less than or equal to 60% predicted tested in patients with:
Prior radiation therapy that, in the judgment of the radiation oncologist, precludes the administration of total body irradiation.