Cyclophosphamide and Fludarabine Followed By Interleukin-2 Gene-Modified Tumor Infiltrating Lymphocytes in Treating Patients With Metastatic Melanoma
Condition: Melanoma (Skin)
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy such as cyclophosphamide and fludarabine use different
      ways to stop tumor cells from dividing so they stop growing or die. Inserting the gene for
      interleukin-2 into a person's tumor infiltrating lymphocytes may make the body build an
      immune response to kill tumor cells. Combining cyclophosphamide and fludarabine with
      gene-modified tumor cells may kill more cancer cells.

      PURPOSE: This phase I/II trial is studying the side effects and best dose of gene-modified
      tumor infiltrating lymphocytes when given together with cyclophosphamide and fludarabine and
      to see how well they work in patients with metastatic melanoma (phase I is closed to accrual
      3/29/06).
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the survival of patients with metastatic melanoma administered interleukin-2
           gene-modified tumor infiltrating lymphocytes after cyclophosphamide and fludarabine.

        -  Compare survival results with prior Surgery Branch studies using adoptive cell therapy
           without the interleukin-2 retroviral vector (SBIL-2) gene.

      Secondary

        -  Determine clinical tumor regression in patients administered interleukin-2 gene-modified
           TIL after cyclophosphamide and fludarabine followed by interleukin-2.

        -  Determine the toxicity profile of this regimen in these patients.

      OUTLINE:

        -  Phase I (closed to accrual as of 3/29/06):

             -  Harvest: TIL are harvested, transduced with IL-2 gene, and expanded in vitro over a
                period of approximately 4 weeks.

             -  Nonmyeloablative preparative regimen (chemotherapy): Patients receive
                cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30
                minutes on days -5 to -1.

             -  Lymphocyte administration: Patients receive IL-2 gene-transduced TIL IV over 20-30
                minutes on day 0. They also receive high-dose IL-2 IV over 15 minutes every 8 hours
                on days 0 -5 (maximum 15 doses). Beginning 1-2 days after lymphocyte
                administration, patients receive filgrastim (G-CSF) subcutaneously (SC) daily, ,
                until blood counts recover.

             -  Retreatment: Patients are re-evaluated every 4-6 weeks. Retreatment depends on
                disease status after each regimen. Patients with dose-limiting toxicity do not
                receive further treatment.

                  -  No response: Patients with stable disease or disease progression after the
                     initial treatment are followed or removed from the study.

                  -  Partial response: Patients with a partial or minor response after the initial
                     treatment may receive retreatment, approximately 2-4 weeks later, with
                     chemotherapy, IL-2 gene-transduced TIL, immunization, and high-dose IL-2 as
                     above, every 4-6 weeks for up to 2 courses provided at least a partial
                     response is documented after each regimen.

                  -  Complete response: Patients with a complete response receive no further
                     treatment.

        -  Phase II: Patients receive treatment and retreatment as in phase I with the MTD of IL-2
           gene-transduced TIL.

      Patients are followed every 3-6 weeks in the absence disease progression.

      PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.
    

Intervention name(s): aldesleukin; filgrastim; incomplete Freund's adjuvant; interleukin-2 gene; therapeutic tumor infiltrating lymphocytes; cyclophosphamide; fludarabine phosphate
Intervention type(s): Biological; Biological; Biological; Biological; Biological; Drug; Drug
Intervention MeSH terms: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2; Freund's Adjuvant
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IV melanoma; recurrent melanoma