Tumor Infiltrating Lymphocytes (TIL Cells) Transduced With An Interleukin-2 (SBIL-2) Gene Following The Administration Of A Nonmyeloablative But Lymphocyte Depleting Regimen in Metastatic Melanoma
- 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.
- 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.
- 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
- Phase II: Patients receive treatment and retreatment as in phase I with the MTD of IL-2
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.
Masking: Open Label, Primary Purpose: Treatment
Steven A. Rosenberg, MD, PhD
NCI - Surgery Branch
United States: Food and Drug Administration
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|
|NCI - Center for Cancer Research||Bethesda, Maryland 20892|