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A Phase II Study Using a Peptide Vaccine With or Without Aldesleukin Following a Lymphodepleting Chemotherapy and Reinfusion of Autologous Lymphocytes Depleted of T Regulatory Lymphocytes in Metastatic Melanoma

Phase 2
18 Years
Not Enrolling
Recurrent Melanoma, Stage IV Melanoma

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Trial Information

A Phase II Study Using a Peptide Vaccine With or Without Aldesleukin Following a Lymphodepleting Chemotherapy and Reinfusion of Autologous Lymphocytes Depleted of T Regulatory Lymphocytes in Metastatic Melanoma


I. Determine the ability of gp100 and MART-1 peptide vaccines with or without a high-dose
interleukin-2 (IL-2), when administered after a nonmyeloablative, lymphodepleting
preparative regimen and reinfusion of autologous CD25+ T-regulatory-depleted lymphocytes, to
mediate tumor regression in patients with metastatic melanoma.


I. Determine the generation of antitumor lymphocytes and the rate of repopulation of CD25+
T-regulatory cells in patients treated with this regimen.

II. Determine the toxicity of this treatment regimen.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo apheresis and in-vitro depletion of T-regulatory cells. Patients
then receive a nonmyeloablative, lymphocyte-depleting preparative regimen comprising
cyclophosphamide IV over 1 hour on days -8 and -7 and fludarabine IV over 15-30 minutes on
days -6 to -2 followed by autologous T-regulatory-depleted lymphocytes IV over 20-30 minutes
on day 0. Patients receive vaccination with gp100:209-217 (210M) and MART-1:27-35 peptides
emulsified in Montanide ISA-51 subcutaneously (SC) on days 0-3, 20-23, 41-44, and 62-65.
Patients also receive filgrastim (G-CSF) SC beginning on day 1 and continuing until blood
counts recover.

ARM II: Patients receive treatment as in arm I. Patients also receive high-dose IL-2 IV over
15 minutes every 8 hours on days 0-4, beginning after the lymphocyte infusion. IL-2
treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed every 1-3 months.

Inclusion Criteria:

- Diagnosis of metastatic melanoma

- No tumor reactive cells available for cell transfer therapy

- Measurable disease

- Previously treated with interleukin-2 (IL-2) and meets 1 of the following criteria:

- No response (progressive disease)

- Recurrent disease

- HLA*0201 positive

- ECOG performance status 0 or 1

- Absolute neutrophil count > 1,000/mm^3

- Platelet count > 100,000/mm^3

- Hemoglobin > 8.0 g/dL

- ALT and AST < 3 times upper limit of normal

- Bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL if Gilbert's disease is present)

- Creatinine ≤ 2.0 mg/dL

- Life expectancy ≥ 3 months

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for up to 4 months after
receiving the preparative regimen

- No active systemic infections, coagulation disorders, or other major medical
illnesses of the cardiovascular, respiratory, or immune system, as evidenced by a
positive stress thallium or comparable test, myocardial infarction, cardiac
arrhythmias, or obstructive or restrictive pulmonary disease

- No autoimmune disease (e.g., autoimmune colitis or Crohn's disease) or primary
immunodeficiency disease

- No HIV positivity

- No hepatitis B or C virus positivity

- No Epstein-Barr virus negativity

- Eligible to receive high-dose IL-2, as evidenced by the following:

- Patients ≥ 50 years of age must have a normal cardiac stress test (e.g., stress
thallium, stress MUGA, dobutamine echocardiogram, or other stress test) AND LVEF
≥ 45%

- Patients with a history of EKG abnormalities, symptoms of cardiac ischemia, or
arrhythmias must have a normal cardiac stress test AND LVEF ≥ 45%

- Patients with a prolonged history of cigarette smoking or symptoms of
respiratory dysfunction must have a normal pulmonary function test, as evidenced
by FEV 1 ≥ 60% of predicted

- At least 4 weeks since prior systemic therapy

- At least 6 weeks since prior nitrosourea therapy

- No concurrent systemic steroid therapy

- Recovered immune competence after prior chemotherapy or radiotherapy

- No prior gp100:209-217 or MART-1:27-35 peptide vaccine

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective clinical response (CR or PR)

Outcome Time Frame:

Up to 2 years

Safety Issue:


Principal Investigator

Steven Rosenberg

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute Surgery Branch


United States: Food and Drug Administration

Study ID:




Start Date:

November 2005

Completion Date:

Related Keywords:

  • Recurrent Melanoma
  • Stage IV Melanoma
  • Melanoma



National Cancer Institute Surgery Branch Bethesda, Maryland  20892-1201