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

Primary Purpose

Recurrent Melanoma, Stage IV Melanoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cyclophosphamide
fludarabine phosphate
therapeutic autologous lymphocytes
in vitro-treated peripheral blood stem cell transplantation
gp100 antigen
MART-1 antigen
incomplete Freund's adjuvant
filgrastim
aldesleukin
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • National Cancer Institute Surgery Branch

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I

Arm II

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Objective clinical response (CR or PR)

Secondary Outcome Measures

Presence of anti-tumor T cells
Recovery of regulatory T cells
Incidence of DLTs and SAEs graded according to CTCAE version 3.0

Full Information

First Posted
March 15, 2006
Last Updated
June 5, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00303836
Brief Title
Vaccine Therapy With or Without Interleukin-2 After Chemotherapy and an Autologous White Blood Cell Infusion in Treating Patients With Metastatic Melanoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Terminated
Study Start Date
November 2005 (undefined)
Primary Completion Date
January 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Melanoma, Stage IV Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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 Title
Arm II
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Other Intervention Name(s)
2-F-ara-AMP, Beneflur, Fludara
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
therapeutic autologous lymphocytes
Other Intervention Name(s)
AL, Autologous Lymphocytes, autologous T cells
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
in vitro-treated peripheral blood stem cell transplantation
Other Intervention Name(s)
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
Intervention Description
Undergo in vitro-treated peripheral blood stem cell transplantation
Intervention Type
Biological
Intervention Name(s)
gp100 antigen
Other Intervention Name(s)
gp100
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
MART-1 antigen
Other Intervention Name(s)
Antigen LB39-AA, Antigen SK29-AA, MART-1, MART-1 Tumor Antigen
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
incomplete Freund's adjuvant
Other Intervention Name(s)
IFA, ISA-51, Montanide ISA 51
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
G-CSF, Neupogen
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
aldesleukin
Other Intervention Name(s)
IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Objective clinical response (CR or PR)
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Presence of anti-tumor T cells
Time Frame
Up to 2 years
Title
Recovery of regulatory T cells
Time Frame
Up to 2 years
Title
Incidence of DLTs and SAEs graded according to CTCAE version 3.0
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Rosenberg
Organizational Affiliation
National Cancer Institute Surgery Branch
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Institute Surgery Branch
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892-1201
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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