Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Metastatic Melanoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	NCI-98-C-0095 NCI-T98-0012, T98-0012, NCT00019487

Special Category: NIH Clinical Center trial

Objectives

1. Determine whether reinfused activated cells alone or in conjunction with high or subcutaneous dose interleukin-2 may result in clinical tumor regression in patients with metastatic melanoma who had previously failed therapy on protocols involving immunization against the gp100 molecule.
2. Determine the survival of infused cells with antitumor activity in these patients.

Entry Criteria

Disease Characteristics:

• Histologically proven metastatic melanoma that has failed therapy on protocols involving immunization against the gp100 molecule



• Measurable or evaluable metastatic disease



• Must be HLA-A201 positive by standard HLA typing

Prior/Concurrent Therapy:

Biologic therapy:

• At least 4 weeks since prior biologic therapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• No concurrent steroid therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• Not specified

Other:

• No concurrent active treatment of brain metastases

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Greater than 3 months

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm³
• Platelet count greater than 100,000/mm³
• Hemoglobin greater than 8.0 g/dL

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• ALT/AST less than 4 times upper limit of normal

Renal:

• Creatinine no greater than 1.6 mg/dL

Cardiovascular:

• For patients randomized to receive interleukin-2:
  • No major medical illnesses of the cardiovascular system

Pulmonary:

• For patients randomized to receive interleukin-2:
  • No major medical illnesses of the pulmonary system

Other:

• HIV negative
• Hepatitis B antigen negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• For patients randomized to receive interleukin-2:
  • No active systemic infection
  • No other major medical illnesses of immune system
  • No coagulation disorders

Expected Enrollment

A total of 91 patients will be accrued for this study over 2 years.

Outline

This is a salvage regimen.

Patients undergo leukopheresis to obtain peripheral blood mononuclear cells or tumor biopsy to obtain tumor infiltrating lymphocytes (TIL). Cells are incubated in the presence of gp209-2M peptide and then harvested and cloned. Patients receive 30-minute IV infusions of these in vitro sensitized cells. Treatment repeats every 2 weeks for 2 courses. An additional cohort of 8 patients receives gp209-2M peptide in Montanide ISA-51 subcutaneously in 2 different sites followed 2 days later by the adoptive transfer of cloned lymphocytes. At 4 to 6 weeks after the treatment courses, patients with stable or regressing disease may be retreated.

Patients with disease progression after 2 courses may receive 2 additional courses of cell infusion followed by interleukin-2 (IL-2) on one of two schedules. One cohort of patients receives IL-2 by intravenous bolus over 15 minutes every 8 hours beginning on the day after cell infusion and continuing for up to 5 days of each treatment course. Another cohort receives IL-2 by daily subcutaneous injections on days 1-12 of each course of therapy. If after 12-16 patients have been treated with cloned cells alone initially and responses are inadequate, subsequent patients entered into this study are randomized to receive the cell infusion followed by IL-2 on one of the two described schedules.

Patients are followed at 4-6 weeks.

Dudley ME, Wunderlich J, Nishimura MI, et al.: Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma. J Immunother 24 (4): 363-73, 2001 Jul-Aug.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Steven Rosenberg, MD, PhD, Protocol chair		Ph: 866-820-4505 Email: sar@nih.gov

Registry Information
Official Title		Treatment of Patients With Metastatic Melanoma Using Cloned Peripheral Blood Lymphocytes Sensitized In Vitro to the gp209-2M Immunodominant Peptide
Trial Start Date		1998-11-04
Registered in ClinicalTrials.gov		NCT00019487
Date Submitted to PDQ		1998-05-13
Information Last Verified		2003-03-14