Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma
Condition: Metastatic Melanoma
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Aldesleukin; Fludarabine; Fludarabine; Cyclophosphamide; Cyclophosphamide; Cyclophosphamide; Young TIL; Pembrolizumab
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Biological; Drug
Intervention description(s): 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).
Other intervention name(s): Proleukin; Fludara; Fludara; Cytoxan; Cytoxan; Cytoxan; Young Tumor Infiltrating Lymphocytes; Keytruda
Intervention MeSH terms: Vidarabine; Aldesleukin; Cyclophosphamide; Pembrolizumab; Fludarabine; Fludarabine phosphate
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Melanoma; Adoptive Cell Therapy