Cyclophosphamide, Fludarabine, and Total-Body Irradiation Followed By Cellular Adoptive Immunotherapy, Autologous Stem Cell Transplantation, and Interleukin-2 in Treating Patients With Metastatic Melanoma
Condition: Melanoma (Skin)
MeSH terms: Melanoma
Intervention: aldesleukin; filgrastim; therapeutic tumor infiltrating lymphocytes; cyclophosphamide; fludarabine phosphate; radiation therapy
Intervention description: high dose: 720,000 IU/kg intravenously over 15 minutes every 8 hours for up to 5 days (maximum 5 doses) or low dose: 250,000 IU/kg subcutaneously daily for 5 days, after a two day rest, 125,000 IU/kg subcutaneously daily for 5 days for five weeks (2 days rest per week); 10 mcg/kg/day daily subcutaneously until neutrophil count >1x10^9/1.; Lymphocytes that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.; 60 mg/kg/day x 2 days intravenously over 1 hour; 25 mg/m^2/day intravenous piggyback daily over 15-20 minutes for 5 days; Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Intervention MeSH terms: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IV melanoma; recurrent melanoma

Summary:

      RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in
      different ways to stop tumor cells from dividing so they stop growing or die. Radiation
      therapy uses high-energy x-rays to damage tumor cells. Biological therapies, such as cellular
      adoptive immunotherapy, work in different ways to stimulate the immune system and stop tumor
      cells from growing. Autologous stem cell transplant may be able to replace immune cells that
      were destroyed by chemotherapy and radiation therapy. Interleukin-2 may stimulate a person's
      lymphocytes to kill tumor cells. Combining chemotherapy, radiation therapy, and biological
      therapy may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine
      together with radiation therapy followed by cellular adoptive immunotherapy, autologous stem
      cell transplant, and interleukin-2 works in treating patients with metastatic melanoma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of metastatic melanoma

          -  Measurable disease

          -  Resected or stable brain metastases are allowed

        PATIENT CHARACTERISTICS:

        Age

          -  18 and over

        Performance status

          -  Eastern Cooperative Oncology Group (ECOG) 0-1

        Life expectancy

          -  At least 3 months

        Hematopoietic

          -  See Immunologic

          -  Absolute neutrophil count > 1,000/mm^3 (without support of filgrastim [G-CSF])

          -  Platelet count > 100,000/mm^3

          -  Hemoglobin ≥ 8 g/dL (transfusion allowed)

          -  No coagulation disorders

        Hepatic

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 times upper
             limit of normal

          -  Bilirubin ≤ 2 mg/dL (< 3 mg/dL in patients with Gilbert's syndrome)

          -  No hepatitis B or C

        Renal

          -  Creatinine ≤ 1.6 mg/dL

        Cardiovascular

          -  Left ventricular ejection fraction (LVEF) ≥ 45% by cardiac stress test*

          -  No active major cardiovascular illness as evidenced by stress thallium or other
             comparable test

          -  No myocardial infarction

          -  No cardiac arrhythmias NOTE: *For patients ≥ 50 years of age receiving high-dose
             interleukin-2 (IL-2) OR patients with a history of electrocardiogram (EKG)
             abnormalities, symptoms of cardiac ischemia, or arrhythmias

        Pulmonary

          -  Forced expiratory volume 1 (FEV_1) ≥ 60% of predicted by pulmonary function test in
             patients with prolonged history of cigarette smoking or symptoms of respiratory
             dysfunction*

          -  No active major respiratory illness

          -  No obstructive or restrictive pulmonary disease NOTE: *For patients receiving
             high-dose IL-2 only

        Immunologic

          -  No active major immunologic illness

          -  No active systemic infections

          -  No primary or secondary immunodeficiency

               -  Fully recovered immune competence after prior chemotherapy or radiotherapy as
                  evidenced by both of the following:

                    -  Absolute neutrophil count > 1,000/mm^3

                    -  No opportunistic infections

          -  Human Immunodeficiency virus (HIV) negative

          -  Epstein-Barr virus positive

        Other

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception during and for 4 months after study
             treatment

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  See Disease Characteristics

        Chemotherapy

          -  At least 6 weeks since prior nitrosourea therapy

          -  No prior cyclophosphamide and fludarabine as part of a preparative regimen on National
             Cancer Institute (NCI) Surgery Branch adoptive cell therapy studies unless sufficient
             numbers of CD34+ stem cells (more than 2 x10^6/kg patient weight) have been obtained
             prior to the administration of chemotherapy

        Endocrine therapy

          -  No concurrent systemic steroid therapy

        Radiotherapy

          -  Not specified

        Surgery

          -  See Disease Characteristics

          -  Prior minor surgery within the past 3 weeks allowed if recovered

        Other

          -  Recovered from all prior therapy

          -  At least 30 days since prior systemic therapy

          -  No other concurrent experimental agents