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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Melanoma (Skin)

Treatments: Biological: gp100 antigen; Biological: MART-1 antigen; Biological: aldesleukin

Study type: Interventional

Funder types: NIH

Identifiers

NCT00019214

NCI-97-C-0046

NCI-97-C-0019

NCI-T96-0046N

CDR0000065234

Details and patient eligibility

About

RATIONALE: Vaccines made from white blood cells treated with antigens may make the body build an immune response to kill melanoma cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Combining vaccine therapy with interleukin-2 may kill more melanoma cells.

PURPOSE: This phase I/II trial is studying the side effects and how well giving vaccine therapy and interleukin-2 works compared to vaccine therapy alone in treating patients with metastatic melanoma that has not responded to previous therapy.

Full description

OBJECTIVES:

• Evaluate the toxicity, immunologic reactivity, and possible therapeutic efficacy of immunization with dendritic cells presenting the MART-1 and gp100 melanoma antigens with or without interleukin-2 in patients with metastatic melanoma.

OUTLINE: This is a dose-escalation study of dendritic cells pulsed with MART-1 and gp100 antigens.

Patients receive vaccinations with dendritic cells pulsed with MART-1 and gp100 antigens, either intralymphatically every 4 weeks for 2 doses, or IV every 3 weeks for 4 doses. Some patients also receive interleukin-2 subcutaneously or IV, over 3-5 days, beginning 24 hours after immunization.

Cohorts of 2-9 patients receive escalating doses of pulsed dendritic cells IV until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Subsequent cohorts receive cells with or without interleukin-2. One cohort may expand to 15 patients to determine the accuracy of immunologic response to the vaccine.

One cohort of 11 patients receives cells intralymphatically without interleukin-2 every 3-4 weeks for 2 courses. Patients with stable disease or who achieve minor, mixed, or partial response may be retreated.

Patients with stable or responding disease undergo a second course of vaccination. Patients who completed treatment with vaccine alone and have stable disease, progressive disease, disease progression after a response, or a partial response with no further improvement may receive 2 additional courses.

PROJECTED ACCRUAL: A total of 10-42 patients will be accrued for this study.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic melanoma that has failed standard effective therapy
• Measurable or evaluable disease
• HLA-A2 positive

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC greater than 3,000/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 8.0 g/dL

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• AST/ALT less than 4 times upper limit of normal
• Negative hepatitis B surface antigen
• No coagulation disorder

Renal:

• Creatinine no greater than 1.6 mg/dL OR
• Creatinine clearance greater than 75 mL/min

Cardiovascular:

• No major cardiovascular disease

Pulmonary:

• No major respiratory disease

Other:

• No major immunological disease
• No penicillin allergy
• HIV negative
• No active systemic infection
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• At least 4 weeks since prior steroid therapy and recovered

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 4 weeks since any other prior therapy and recovered