Cyclophosphamide and Fludarabine Followed By Interleukin-2 Gene-Modified Tumor Infiltrating Lymphocytes in Treating Patients With Metastatic Melanoma

Melanoma (Skin) Clinical Trial

Official title: 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

Status Completed

Clinical Trial 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).

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

• NCT number: NCT00062036
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 2003
• Completion date: September 2008