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Aldesleukin With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Melanoma

Primary Purpose

Recurrent Melanoma, Stage IIIA Skin Melanoma, Stage IIIB Skin Melanoma

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Aldesleukin
gp100 Antigen
Montanide ISA 51 VG
Quality-of-Life Assessment
Questionnaire Administration
Laboratory Biomarker Analysis
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: Any patient with measurable metastatic (stage IV or locally advanced stage III) cutaneous melanoma and an expected survival of greater than three months will be considered Serum creatinine of 1.6 mg/dl or less Total bilirubin 1.6 mg/dl or less White blood cell (WBC) 3000/mm^3 or greater Platelet count 90,000 mm^3 or greater Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less then three times normal Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Patients of both genders must be willing to practice effective birth control during this trial Pathologic confirmation of cutaneous melanoma; patients may enter the study with a pathologic diagnosis of cutaneous melanoma from any institution; all slides will be reviewed at National Institutes of Health (NIH) (department of Anatomic Pathology) and if the diagnosis is not confirmed, the patient will be excluded from the study Tissue type human leukocyte antigen (HLA) A0201 Exclusion Criteria: Patients who have types of melanoma other than cutaneous, i.e. ocular or mucosal Patients who are undergoing or have undergone in the past 4 weeks any other form of therapy except surgery for their cancer, including radiation therapy to any site Patients who have active systemic infections, coagulation disorders, autoimmune disease or history of other major medical illnesses such as insulin dependent diabetes mellitus, cardiac ischemia, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary diseases and inflammatory bowel disorders Patients who have significant psychiatric disease which in the opinion of the principal investigator would prevent adequate informed consent or render immunotherapy unsafe or contraindicated Patients who require steroid therapy or steroid-containing compounds, or have used systemic steroids in the past 4 weeks, or have used topical or inhalational steroids in the past 2 weeks Patients who are pregnant Patients who are known to be positive for viral hepatitis B or C (hepatitis B surface antigen [HBsAg] or anti hepatitis C virus [HCV]) or human immunodeficiency virus (HIV) (HIV antibody) Patients who have any form of primary or secondary immunodeficiency Patients who have received previous high dose IL-2 (> 600,000 IU/kg) Patients who have received previous gp100 vaccines Patients who have an abnormal stress cardiac test (stress thallium, stress multi gated acquisition scan [MUGA], dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) Patients who have abnormal pulmonary function tests (forced expiratory volume in one second [FEV1] < 65% or forced vital capacity [FVC] < 65% of predicted) Patients who have brain metastasis or history of brain metastasis No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years

Sites / Locations

  • University of Alabama at Birmingham
  • Mayo Clinic in Arizona
  • Kaiser Permanente Medical Center
  • University of Colorado Cancer Center - Anschutz Cancer Pavilion
  • Lakeland Regional Cancer Center
  • Emory University/Winship Cancer Institute
  • Northwestern University
  • Rush University Medical Center
  • Advocate Lutheran General Hospital.
  • IU Health Goshen Center for Cancer Care
  • The James Graham Brown Cancer Center at University of Louisville
  • National Institutes of Health
  • Carolinas Medical Center
  • The Christ Hospital
  • Ohio State University Comprehensive Cancer Center
  • Saint Luke's University Hospital-Bethlehem Campus
  • Penn State Milton S Hershey Medical Center
  • M D Anderson Cancer Center
  • Aurora Saint Luke's Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I (aldesleukin)

Arm II (gp100 antigen in Montanide IDA-51 and aldesleukin)

Arm Description

Patients receive aldesleukin IV over 15 minutes every 8 hours for 12 doses. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.

Patients receive gp100 antigen emulsified in Montanide ISA-51 SC on day 1. Patients also receive aldesleukin as in Arm I beginning on day 2. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.

Outcomes

Primary Outcome Measures

Best Response Rate (Partial Response [PR] + Complete Response [CR])
A complete response (CR) was defined as the disappearance of all clinical evidence of disease for at least 4 weeks. A partial response (PR) was defined as a 50% or greater decrease in the sum of the products of perpendicular diameters of all measurable lesions for at least one month. No new lesions could appear, and none could increase 25% or more.

Secondary Outcome Measures

Progression Free Survival
Progression free survival was compared between groups by means of Kaplan-Meier curves using the log-rank test to evaluate the significance of the difference between the arms.
Change in T-cell Precursors
To measure change in T-cell precursors, PBMC were tested for reactivity by measuring gamma-interferon release after overnight coculture with peptide pulsed T2 cells. PBMC obtained after 4 cycles of study treatment were compared to pre treatment PBMC. A positive assay was defined as greater than 100pg/ml gamma-interferon release and at least twice the release (including all control peptides) by post treatment PBMC compared to pre treatment PBMC.
Change in Quality of Life (QOL) Score Assessed by the FACT-G (Functional Assessment of Cancer Therapy- General), FACT-F (Functional Assessment of Cancer Therapy- Fatigue), SF-36 (Short Form 36) and SDS (Symptom Distress Scale)
QOL was measured before and after 2 cycles of treatment using 4 measures: FACT-G is a 27 item measure of QOL. A total score is calculated by summing across responses on a 5 point scale and ranges from 0-135, with higher scores indicating better QOL. FACT-F is 13 item measure of fatigue. A total score is calculated by summing across responses on a 5 point scale. Total score ranges from 0-52, with higher scores indicating less fatigue. SF-36 is a 36 item measure of self-reported health status. SF-36 is comprised of 8 subscales: physical function, role physical, bodily pain vitality, role emotional function, mental health, social function and general health. Summated scores range from 0-100, with higher scores indicating a better health state. SDS is a 13 item measure of symptom distress. A total score is calculated by summing across responses on a 5 point scale. Total score ranges from 13 to 65, with higher scores indicating more symptom distress.

Full Information

First Posted
July 11, 2001
Last Updated
November 16, 2017
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00019682
Brief Title
Aldesleukin With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Melanoma
Official Title
A Phase III Multi-Institutional Randomized Study of Immunization With the gp100: 209-217 (210M) Peptide Followed by High Dose IL-2 vs. High Dose IL-2 Alone in Patients With Metastatic Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
December 1999 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2011 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized phase III trial studies aldesleukin with vaccine therapy to see how well it works compared to aldesleukin alone in treating patients with melanoma that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Aldesleukin may stimulate a person's white blood cells to kill melanoma cells. Vaccines may make the body build an immune response to kill tumor cells. It is not yet known whether combining aldesleukin with vaccine therapy is more effective than aldesleukin alone in treating melanoma.
Detailed Description
PRIMARY OBJECTIVES: I. To identify whether the addition of the peptide vaccine to high dose interleukin (IL)-2 (aldesleukin) can result in a clinical response rate which may be superior to that found in similar patients treated with high dose IL-2 alone. SECONDARY OBJECTIVES: I. To evaluate the toxicity profile of patients treated on this trial, according to the regimen received. II. To compare the disease free/progression free survival of patients treated on both arms of the study. III. To determine the immunologic response experienced by patients who have received the peptide vaccination, as measured by changes in T-cell precursors from before to after treatment. IV. To evaluate the quality of life of patients before and after high-dose IL-2. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive aldesleukin intravenously (IV) over 15 minutes every 8 hours for 12 doses. ARM II: Patients receive gp100 antigen emulsified in Montanide ISA-51 subcutaneously (SC) on day 1. Patients also receive aldesleukin as in Arm I beginning on day 2. In both arms, treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses. After completion of treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
185 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (aldesleukin)
Arm Type
Experimental
Arm Description
Patients receive aldesleukin IV over 15 minutes every 8 hours for 12 doses. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
Arm Title
Arm II (gp100 antigen in Montanide IDA-51 and aldesleukin)
Arm Type
Experimental
Arm Description
Patients receive gp100 antigen emulsified in Montanide ISA-51 SC on day 1. Patients also receive aldesleukin as in Arm I beginning on day 2. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
Intervention Type
Biological
Intervention Name(s)
Aldesleukin
Other Intervention Name(s)
Ro-236019
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
gp100 Antigen
Other Intervention Name(s)
gp 100, gp100
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
Montanide ISA 51 VG
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Best Response Rate (Partial Response [PR] + Complete Response [CR])
Description
A complete response (CR) was defined as the disappearance of all clinical evidence of disease for at least 4 weeks. A partial response (PR) was defined as a 50% or greater decrease in the sum of the products of perpendicular diameters of all measurable lesions for at least one month. No new lesions could appear, and none could increase 25% or more.
Time Frame
Up to 12 years
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
Progression free survival was compared between groups by means of Kaplan-Meier curves using the log-rank test to evaluate the significance of the difference between the arms.
Time Frame
From the date of randomization until documentation of progression or last follow up, assessed up to 12 years
Title
Change in T-cell Precursors
Description
To measure change in T-cell precursors, PBMC were tested for reactivity by measuring gamma-interferon release after overnight coculture with peptide pulsed T2 cells. PBMC obtained after 4 cycles of study treatment were compared to pre treatment PBMC. A positive assay was defined as greater than 100pg/ml gamma-interferon release and at least twice the release (including all control peptides) by post treatment PBMC compared to pre treatment PBMC.
Time Frame
Baseline to up to 12 years
Title
Change in Quality of Life (QOL) Score Assessed by the FACT-G (Functional Assessment of Cancer Therapy- General), FACT-F (Functional Assessment of Cancer Therapy- Fatigue), SF-36 (Short Form 36) and SDS (Symptom Distress Scale)
Description
QOL was measured before and after 2 cycles of treatment using 4 measures: FACT-G is a 27 item measure of QOL. A total score is calculated by summing across responses on a 5 point scale and ranges from 0-135, with higher scores indicating better QOL. FACT-F is 13 item measure of fatigue. A total score is calculated by summing across responses on a 5 point scale. Total score ranges from 0-52, with higher scores indicating less fatigue. SF-36 is a 36 item measure of self-reported health status. SF-36 is comprised of 8 subscales: physical function, role physical, bodily pain vitality, role emotional function, mental health, social function and general health. Summated scores range from 0-100, with higher scores indicating a better health state. SDS is a 13 item measure of symptom distress. A total score is calculated by summing across responses on a 5 point scale. Total score ranges from 13 to 65, with higher scores indicating more symptom distress.
Time Frame
Baseline to up to 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Any patient with measurable metastatic (stage IV or locally advanced stage III) cutaneous melanoma and an expected survival of greater than three months will be considered Serum creatinine of 1.6 mg/dl or less Total bilirubin 1.6 mg/dl or less White blood cell (WBC) 3000/mm^3 or greater Platelet count 90,000 mm^3 or greater Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less then three times normal Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Patients of both genders must be willing to practice effective birth control during this trial Pathologic confirmation of cutaneous melanoma; patients may enter the study with a pathologic diagnosis of cutaneous melanoma from any institution; all slides will be reviewed at National Institutes of Health (NIH) (department of Anatomic Pathology) and if the diagnosis is not confirmed, the patient will be excluded from the study Tissue type human leukocyte antigen (HLA) A0201 Exclusion Criteria: Patients who have types of melanoma other than cutaneous, i.e. ocular or mucosal Patients who are undergoing or have undergone in the past 4 weeks any other form of therapy except surgery for their cancer, including radiation therapy to any site Patients who have active systemic infections, coagulation disorders, autoimmune disease or history of other major medical illnesses such as insulin dependent diabetes mellitus, cardiac ischemia, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary diseases and inflammatory bowel disorders Patients who have significant psychiatric disease which in the opinion of the principal investigator would prevent adequate informed consent or render immunotherapy unsafe or contraindicated Patients who require steroid therapy or steroid-containing compounds, or have used systemic steroids in the past 4 weeks, or have used topical or inhalational steroids in the past 2 weeks Patients who are pregnant Patients who are known to be positive for viral hepatitis B or C (hepatitis B surface antigen [HBsAg] or anti hepatitis C virus [HCV]) or human immunodeficiency virus (HIV) (HIV antibody) Patients who have any form of primary or secondary immunodeficiency Patients who have received previous high dose IL-2 (> 600,000 IU/kg) Patients who have received previous gp100 vaccines Patients who have an abnormal stress cardiac test (stress thallium, stress multi gated acquisition scan [MUGA], dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) Patients who have abnormal pulmonary function tests (forced expiratory volume in one second [FEV1] < 65% or forced vital capacity [FVC] < 65% of predicted) Patients who have brain metastasis or history of brain metastasis No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Douglas Schwartzentruber
Organizational Affiliation
IU Health Goshen Center for Cancer Care
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Kaiser Permanente Medical Center
City
Riverside
State/Province
California
ZIP/Postal Code
92505
Country
United States
Facility Name
University of Colorado Cancer Center - Anschutz Cancer Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Lakeland Regional Cancer Center
City
Lakeland
State/Province
Florida
ZIP/Postal Code
33805
Country
United States
Facility Name
Emory University/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Advocate Lutheran General Hospital.
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068
Country
United States
Facility Name
IU Health Goshen Center for Cancer Care
City
Goshen
State/Province
Indiana
ZIP/Postal Code
46526
Country
United States
Facility Name
The James Graham Brown Cancer Center at University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
National Institutes of Health
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
The Christ Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Saint Luke's University Hospital-Bethlehem Campus
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18015
Country
United States
Facility Name
Penn State Milton S Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033-0850
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Aurora Saint Luke's Medical Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21631324
Citation
Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, Gailani F, Riley L, Conlon K, Pockaj B, Kendra KL, White RL, Gonzalez R, Kuzel TM, Curti B, Leming PD, Whitman ED, Balkissoon J, Reintgen DS, Kaufman H, Marincola FM, Merino MJ, Rosenberg SA, Choyke P, Vena D, Hwu P. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011 Jun 2;364(22):2119-27. doi: 10.1056/NEJMoa1012863.
Results Reference
derived

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Aldesleukin With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Melanoma

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