Protocol Number: 97-C-0019

Title:

Phase I/II Study in Patients with Metastatic Melanoma of Immunization with Dendritic Cells Presenting Epitopes Derived from the Melanoma Associated Antigen MART-1 and gp100

Number:

97-C-0019

Summary:

This is a dose escalation study.

Patients are given separate doses of dendritic cells (DC) pulsed with either the MART-1 or G9-209-2M peptides. Patients receive four successive immunizations of an equal number of DCs every 3 weeks. When the maximum tolerated dose (MTD) or the highest dose of DCs to be given is reached, interleukin-2 (IL-2) is administered according to one of three dosage schedules. IL-2 is begun within 24 hours after DC administration.

If 2 or more patients out of 6 at any dose level exhibit dose limiting toxicity, the preceding dose level will be considered the MTD.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Patients must have evidence of measurable or evaluable metastatic melanoma. Patients with completely resected metastatic disease are also eligible.

Age greater than or equal to 18 years.

Patients must have undergone standard HLA typing of peripheral blood lymphocytes and be HLA-A2 positive.

Patients must have a histologic diagnosis of melanoma confirmed by pathologists at the NIH.

Clinical performance status of ECOG 0,1 or 2.

White blood cell count must be greater than 3,000/mm(3).

Platelet count greater than 100,000/mm(3).

Hemoglobin greater than 8.0 g/dl.

Serum ALT/AST less than four times the upper limit of normal.

Serum creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than 75 ml/min.

Bilirubin less than or equal to 2.0 mg/dl.

More than four weeks must have elapsed since any prior therapy.

Women of child-bearing potential must have a negative pregnancy test and be willing to use an effective method of contraception during the trial.

Life expectancy greater than three months.

No steroid therapy required during the last month.

Seronegative for HIV antibody.

Seronegative for hepatitis B antigen.

No active systemic infection, coagulation disorder or other major medical illness of the cardiovascular, respiratory or immune system.

Patients must be able to provide informed consent.

Patients must have recovered from toxicities from previous therapies.

EXCLUSION CRITERIA:

All patients not eligible according to inclusion criteria.

Allergy to Penicillin.

ELIGIBILITY FOR ADMINISTRATION OF IL-2:

Patients with EKG abnormalities, symptoms of cardiac ischemia or arrhythmias or age greater than 50 years will have a normal stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram or other stress test).

Patients with recent prolonged history of cigarette smoking or symptoms of respiratory dysfunction must have a normal pulmonary function test as evidenced by a FEV(1) greater than 60% predicted.

Patients may not have active major medical illnesses such as cardiac ischemia, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.

Patients may not have received prior high dose IL-2 therapy (greater than or equal to 600,000 IU/kg).

Patients must be willing to sign a Durable Power of Attorney.

Special Instructions:

Many protocols are potentially hazardous, are intended only for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this protocol should be consulted before using this protocol. Dose and schedule modifications are required for patients who develop gastrointestinal, hematologic, neurologic, and biochemical (renal, hepatic, etc.) and/or other abnormalities after the administration of therapy. Additionally, Federal regulations for the protection of human subjects require approval of clinical trials by your local Institutional Review Board.

Keywords:

Immunotherapy

Vaccination

Interleukin-2

Antigen Presenting Cells

Advanced Cancer

Recruitment Keywords:

None

Conditions:

Melanoma

Neoplasm Metastasis

Investigational Drug(s):

Interleukin-2

Interleukin-4

GM-CSF

MART-1: 26-35(27L)

G9-209-2M Peptide

rhCD40 Ligand

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Induction of tumor reactive CTL from peripheral blood and tumor infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1

Recognition of multiple epitopes in the human melanoma antigen gp 100 by peripheral blood lymphocytes stimulated in vitro with synthetic peptides

Karnofsky Memorial Lecture The immunotherapy and gene therapy of cancer

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

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Bethesda, Maryland 20892. Last update: 10/19/2004