Background: * The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 400 patients with melanoma. * In this trial, we are determining if there is a difference in the response between patients who have received prior anti-programmed cell death-1 (PD-1) treatment to those who have not received this prior ant-PD1 treatment. Objectives: \- To determine if there is a difference in the rate of response between patients who have received prior anti-PD1 and those who have not. Eligibility: \- Individuals at least 18 years and less than or equal to 70 years of age who have metastatic melanoma. Design: * Work up stage: Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. * Surgery: Surgery or biopsy will be performed to obtain tumor from which to grow white blood cells. White blood cells will be grown from the tumor in the laboratory. * Leukapheresis: Participants will have leukapheresis to collect additional white blood cells. (Leukapheresis is a common procedure which removes only the white blood cells from the patient.) * Treatment: Participants will receive standard dose chemotherapy to prepare their immune system to accept the white blood cells. Participants will receive an infusion of their own white blood cells grown from tumor. They will also receive aldesleukin for up to five days to boost the immune system s response to the white blood cells. They will stay in the hospital for about 4 weeks for the treatment. * Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.
Background: * Adoptive cell therapy (ACT) using autologous tumor infiltrating lymphocytes can mediate the regression of bulky metastatic melanoma when administered along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen consisting of cyclophosphamide and fludarabine. * In a series of consecutive trials using this chemotherapy preparative regimen alone or with 2 Gray (Gy) or 12 Gy total body irradiation (TBI) objective response rates using Response Evaluation Criteria In Solid Tumors (RECIST) criteria were 49%, 52%, and 72%, respectively. Of the 20 complete regressions seen in this trial, 19 are on-going at 70 to 114 months. * The chemotherapy alone preparative regimen required in-patient treatment and was associated with significant neutropenia and thrombocytopenia requiring multiple transfusions and treatment for febrile neutropenia. Objectives: * With amendment D, to determine if there is a difference in the rate of response between patients who have received prior anti-PD1 and those who have not; both groups will receive non-myeloablative lymphoid depleting preparative regimen followed by autologous young tumor infiltrating lymphocytes (TIL) and administration of high dose aldesleukin. * To determine the toxicity of the treatment. Eligibility: * Age greater than or equal to 18 and less than or equal to 70 years * Evaluable metastatic melanoma * Metastatic melanoma lesion suitable for surgical resection for the preparation of TIL * No contraindications to high-dose aldesleukin administration * No concurrent major medical illnesses or any form of immunodeficiency Design: * Patients with metastatic melanoma will have lesions resected and after TIL growth is established, patients will receive ACT with TIL plus aldesleukin following high dose chemotherapy preparative regimen. * Up to 64 patients may be enrolled over 4-5 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
33
720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days
30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days.
60 mg/kg/day X 2 days intravenous (IV)
Days -5 to -3 (low-dose arm):30 mg/kg IV over 60 minutes for 2 days
Days -5 to -3 (low-dose arm): 300 mg/m\^2 IV over 60 minutes.
Day 0: Cells will be infused intravenously (IV)
2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Number of participants with Grades 3-5 treatment-related adverse events were compared in Arm 1N and Arm 1P; and adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening, and Grade 5 is death related to adverse event.
Time frame: 30 days after end of treatment
Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
Clinical response to treatment was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST v1.0). Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive Disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.
Time frame: 4 weeks after cell infusion, then every 3 months x 3 and then every 6 months for 5 years, then per Principal Investigator (PI) discretion up to 5 years or disease progression
Overall Response Rate (ORR)
Overall response is the best response recorded from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.0). Progression is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Date of cells until time of disease progression, up to approximately 67.2 months.
Number of Treatment-related Adverse Events for Participants Who Received Pembrolizumab
Number of treatment-related adverse events for participants who received pembrolizumab. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Time frame: Date treatment consent signed until approximately 4 weeks following last dose of Pembrolizumab, up to 4 weeks
Progression-free Survival (PFS)
PFS is defined as the time to disease progression following the start of treatment, and time to death following the start of treatment. Progression was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.0 and is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Date of cells until time of disease progression up to approximately 67.2 months.
Overall Survival
Overall survival is defined as the time from treatment start date until date of death, or date last known alive.
Time frame: Date of cells until time to death, up until 90.1 months.
Overall Survival
Overall survival is defined as the time from treatment start date until date of death, or date last known alive.
Time frame: An average of 25.6 months.
Overall Progression Free Survival (PFS)
PFS is defined as the time to disease progression following the start of treatment, and time to death following the start of treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 and is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Time to progression and time to death, approximately up to 67.2 months.
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