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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00303836
First received: March 15, 2006
Last updated: June 5, 2013
Last verified: June 2013

March 15, 2006
June 5, 2013
November 2005
January 2007   (final data collection date for primary outcome measure)
Objective clinical response (CR or PR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00303836 on ClinicalTrials.gov Archive Site
  • Presence of anti-tumor T cells [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Recovery of regulatory T cells [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Incidence of DLTs and SAEs graded according to CTCAE version 3.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
Vaccine Therapy With or Without Interleukin-2 After Chemotherapy and an Autologous White Blood Cell Infusion in Treating Patients With Metastatic Melanoma
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Melanoma
  • Stage IV Melanoma
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: fludarabine phosphate
    Given IV
    Other Names:
    • 2-F-ara-AMP
    • Beneflur
    • Fludara
  • Biological: therapeutic autologous lymphocytes
    Given IV
    Other Names:
    • AL
    • Autologous Lymphocytes
    • autologous T cells
  • Procedure: in vitro-treated peripheral blood stem cell transplantation
    Undergo in vitro-treated peripheral blood stem cell transplantation
    Other Names:
    • 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
  • Biological: gp100 antigen
    Given SC
    Other Name: gp100
  • Biological: MART-1 antigen
    Given SC
    Other Names:
    • Antigen LB39-AA
    • Antigen SK29-AA
    • MART-1
    • MART-1 Tumor Antigen
  • Biological: incomplete Freund's adjuvant
    Given SC
    Other Names:
    • IFA
    • ISA-51
    • Montanide ISA 51
  • Biological: filgrastim
    Given SC
    Other Names:
    • G-CSF
    • Neupogen
  • Biological: aldesleukin
    Given IV
    Other Names:
    • IL-2
    • Proleukin
    • recombinant human interleukin-2
    • recombinant interleukin-2
  • Experimental: 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.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: fludarabine phosphate
    • Biological: therapeutic autologous lymphocytes
    • Procedure: in vitro-treated peripheral blood stem cell transplantation
    • Biological: gp100 antigen
    • Biological: MART-1 antigen
    • Biological: incomplete Freund's adjuvant
    • Biological: filgrastim
  • Experimental: 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.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: fludarabine phosphate
    • Biological: therapeutic autologous lymphocytes
    • Procedure: in vitro-treated peripheral blood stem cell transplantation
    • Biological: gp100 antigen
    • Biological: MART-1 antigen
    • Biological: incomplete Freund's adjuvant
    • Biological: filgrastim
    • Biological: aldesleukin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
58
Not Provided
January 2007   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00303836
NCI-2012-02684, P6574, NCI-06-C-0028, CDR0000459683, NCI-7547, NCI-P6574
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Steven Rosenberg National Cancer Institute Surgery Branch
National Cancer Institute (NCI)
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP