Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma
Condition: Metastatic Melanoma
MeSH terms: Melanoma
Intervention: Aldesleukin; Fludarabine; Fludarabine; Cyclophosphamide; Cyclophosphamide; Cyclophosphamide; Young TIL; Pembrolizumab
Intervention description: 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).
Intervention MeSH terms: Vidarabine; Aldesleukin; Cyclophosphamide; Pembrolizumab; Fludarabine; Fludarabine phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Melanoma; Adoptive Cell Therapy

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.
    

Eligibility criteria:

        -INCLUSION CRITERIA:

          1. Measurable metastatic melanoma with at least one lesion that is resectable for tumor
             infiltrating lymphocytes (TIL) generation and at least one other lesion that can be
             measured by Response Evaluation Criteria In Solid Tumors (RECIST) criteria.

          2. Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of
             National Cancer Institute (NCI).

          3. Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and
             asymptomatic are eligible. Lesions that have been treated with stereotactic
             radiosurgery must be clinically stable for 1 month after treatment for the patient to
             be eligible. Patients with surgically resected brain metastases are eligible.

          4. Greater than or equal to 18 years of age and less than or equal to 70 years of age.

          5. Ability of subject to understand and the willingness to sign the Informed Consent
             Document

          6. Willing to sign a durable power of attorney.

          7. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2.

          8. 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 treatment.

          9. 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
                  are less responsive to the experimental treatment and more susceptible to its
                  toxicities.)

               -  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 (HCV) ribonucleic acid (RNA) negative.

         10. Women of child-bearing potential must have a negative pregnancy test because of the
             potentially dangerous effects of the treatment on the fetus.

         11. Hematology:

               -  Absolute neutrophil count greater than 1000/mm(3) without the support of
                  filgrastim

               -  White blood cell (WBC) greater than or equal to 3000/mm(3)

               -  Platelet count greater than or equal to 100,000/mm(3)

               -  Hemoglobin > 8.0 g/dl

         12. Chemistry:

               -  Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than
                  or equal to 2.5 times the upper limit of normal

               -  Serum Creatinine less than or equal to 1.6 mg/dl

               -  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.

         13. 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 must have progressive 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.

         14. Subjects must be co-enrolled in 03-C-0277

        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. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
             Disease).

          3. 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).

          4. Active systemic infections, (e.g.: requiring anti-infective treatment), coagulation
             disorders or any other active major medical illnesses.

          5. Concurrent systemic steroid therapy.

          6. History of severe immediate hypersensitivity reaction to any of the agents used in
             this study.

          7. History of coronary revascularization or ischemic symptoms.

          8. Any patient known to have an left ventricular ejection fraction (LVEF) less than or
             equal to 45%

          9. Documented LVEF of less than or equal to 45%, note: testing is required in patients
             with:

               -  Age greater than or equal to 65 years old

               -  Clinically significant atrial and or ventricular arrhythmias including but not
                  limited to: atrial fibrillation, ventricular tachycardia, second or third degree
                  heart block or history of ischemic heart disease or chest pain.

         10. Patients who are receiving other investigational agents

         11. Documented forced expiratory volume (FEV1) less than or equal to 60% predicted tested
             in patients with:

               -  A prolonged history of cigarette smoking (20 pack (pk)/year of smoking within the
                  past 2 years).

               -  Symptoms of respiratory dysfunction