Vaccine Therapy With or Without Interleukin-2 After Chemotherapy and an Autologous White Blood Cell Infusion in Treating Patients With Metastatic Melanoma

NCT ID: NCT00303836

Last Updated: 2013-06-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30

Brief Summary

This randomized phase II trial is studying how well giving vaccine therapy with or without interleukin-2 after chemotherapy and an autologous white blood cell infusion works in treating patients with metastatic melanoma. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy with interleukin-2, chemotherapy, and an autologous white blood cell infusion may be a more effective treatment for metastatic melanoma.

Detailed Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

Conditions

Recurrent Melanoma; Stage IV Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

Given IV

fludarabine phosphate

Intervention Type: DRUG

Given IV

therapeutic autologous lymphocytes

Intervention Type: BIOLOGICAL

Given IV

in vitro-treated peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Undergo in vitro-treated peripheral blood stem cell transplantation

gp100 antigen

Intervention Type: BIOLOGICAL

Given SC

MART-1 antigen

Intervention Type: BIOLOGICAL

Given SC

incomplete Freund's adjuvant

Intervention Type: BIOLOGICAL

Given SC

filgrastim

Intervention Type: BIOLOGICAL

Given SC

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.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

Given IV

fludarabine phosphate

Intervention Type: DRUG

Given IV

therapeutic autologous lymphocytes

Intervention Type: BIOLOGICAL

Given IV

in vitro-treated peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Undergo in vitro-treated peripheral blood stem cell transplantation

gp100 antigen

Intervention Type: BIOLOGICAL

Given SC

MART-1 antigen

Intervention Type: BIOLOGICAL

Given SC

incomplete Freund's adjuvant

Intervention Type: BIOLOGICAL

Given SC

filgrastim

Intervention Type: BIOLOGICAL

Given SC

aldesleukin

Intervention Type: BIOLOGICAL

Given IV

Interventions

cyclophosphamide

Given IV

Intervention Type: DRUG

fludarabine phosphate

Given IV

Intervention Type: DRUG

therapeutic autologous lymphocytes

Given IV

Intervention Type: BIOLOGICAL

in vitro-treated peripheral blood stem cell transplantation

Undergo in vitro-treated peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

gp100 antigen

Given SC

Intervention Type: BIOLOGICAL

MART-1 antigen

Given SC

Intervention Type: BIOLOGICAL

incomplete Freund's adjuvant

Given SC

Intervention Type: BIOLOGICAL

filgrastim

Given SC

Intervention Type: BIOLOGICAL

aldesleukin

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

CPM; CTX; Cytoxan; Endoxan; Endoxana; 2-F-ara-AMP; Beneflur; Fludara; AL; Autologous Lymphocytes; autologous T cells; in vitro-treated PBPC transplantation; in vitro-treated PBSC; in vitro-treated peripheral blood progenitor cell transplantation; PBPC transplantation, in vitro-treated; peripheral blood progenitor cell transplantation, in vitro-treated; gp100; Antigen LB39-AA; Antigen SK29-AA; MART-1; MART-1 Tumor Antigen; IFA; ISA-51; Montanide ISA 51; G-CSF; Neupogen; IL-2; Proleukin; recombinant human interleukin-2; recombinant interleukin-2

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven Rosenberg

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute Surgery Branch

Locations

National Cancer Institute Surgery Branch

Bethesda, Maryland, United States

Countries

United States

Other Identifiers

P6574

Identifier Type: -

Identifier Source: secondary_id

NCI-06-C-0028

Identifier Type: -

Identifier Source: secondary_id

CDR0000459683

Identifier Type: -

Identifier Source: secondary_id

NCI-7547

Identifier Type: -

Identifier Source: secondary_id

NCI-P6574

Identifier Type: -

Identifier Source: secondary_id

NCI-2012-02684

Identifier Type: -

Identifier Source: org_study_id

NCT00255203

Identifier Type: -

Identifier Source: nct_alias