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
  Purpose

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.


Condition Intervention Phase
Recurrent Melanoma
Stage IV Melanoma
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
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective clinical response (CR or PR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 58
Study Start Date: November 2005
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303836

Locations
United States, Maryland
National Cancer Institute Surgery Branch
Bethesda, Maryland, United States, 20892-1201
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Rosenberg National Cancer Institute Surgery Branch
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00303836     History of Changes
Obsolete Identifiers: NCT00255203
Other Study ID Numbers: NCI-2012-02684, P6574, NCI-06-C-0028, CDR0000459683, NCI-7547, NCI-P6574
Study First Received: March 15, 2006
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Aldesleukin
Interleukin-2
Freund's Adjuvant
Lenograstim
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Adjuvants, Immunologic
Analgesics, Non-Narcotic
Analgesics

ClinicalTrials.gov processed this record on August 19, 2014