Ipilimumab With or Without High-Dose Recombinant Interferon Alfa-2b in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

A Randomized Phase II Study of Ipilimumab at 3 mg/kg or 10 mg/kg Alone or in Combination With High Dose Interferon-Alpha in Advanced Melanoma

This randomized phase II trial studies how well ipilimumab with or without high-dose recombinant interferon alpha-2b works in treating patients with stage III-IV melanoma that cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab, may block tumor growth by targeting certain cells. Recombinant interferon alfa-2b may interfere with the growth of tumor cells. It is not yet known whether ipilimumab is more effective with or without high-dose recombinant interferon alfa-2b in treating melanoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Stage IV Cutaneous Melanoma AJCC v6 and v7; Recurrent Melanoma; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Ipilimumab; Biological: Recombinant Interferon Alfa-2b

Detailed Description

PRIMARY OBJECTIVES:

I. Test the hypothesis that the combination of ipilimumab and high-dose interferon-alpha 2b (HDI [recombinant interferon alfa-2b]) will improve progression free survival (PFS) of patients with advanced metastatic melanoma as compared to ipilimumab alone (across ipilimumab treatment status).

SECONDARY OBJECTIVES:

I. Test the hypothesis that the combination of ipilimumab and HDI will prove to be safe and tolerable.

II. Within the constraints of the sample size, attempt to test the hypotheses that (1) ipilimumab 10 mg/kg will lead to improved PFS in comparison to ipilimumab 3 mg/kg (across HDI treatment status); (2) the combination of ipilimumab and HDI will improve overall survival (OS) of patients with advanced metastatic melanoma as compared to ipilimumab alone (across ipilimumab treatment status) and (3) ipilimumab 10 mg/kg will lead to improved OS in comparison to ipilimumab 3 mg/kg (across HDI treatment status).

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM A:

INDUCTION PHASE: Patients receive higher dose ipilimumab intravenously (IV) over 90 minutes once every 3 weeks for 4 doses and recombinant interferon alfa-2b IV over 20 minutes 5 days a week for 4 weeks and then subcutaneously (SC) 3 times weekly for 8 weeks.

MAINTENANCE PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24 and recombinant interferon alfa-2b SC 3 times weekly for 48 weeks.

ARM B:

INDUCTION PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses.

MAINTENANCE PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24.

ARM C:

INDUCTION PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses and recombinant interferon alfa-2b IV over 20 minutes 5 days a week for 4 weeks and then SC 3 times weekly for 8 weeks.

MAINTENANCE PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24 and recombinant interferon alfa-2b SC 3 times weekly for 48 weeks.

ARM D:

INDUCTION PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses.

MAINTENANCE PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually for up to 5 years.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers-Aurora
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Boulder, Colorado, United States, 80303
      • Boulder Community Foothills Hospital
    • Boulder, Colorado, United States, 80304
      • Rocky Mountain Cancer Centers-Boulder
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Colorado Springs, Colorado, United States, 80907
      • Rocky Mountain Cancer Centers-Penrose
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
    • Denver, Colorado, United States, 80222
      • Western States Cancer Research NCORP
    • Denver, Colorado, United States, 80218
      • Saint Joseph Hospital - Cancer Centers of Colorado
    • Denver, Colorado, United States, 80210
      • AdventHealth Porter
    • Englewood, Colorado, United States, 80113
      • Mountain Blue Cancer Care Center - Swedish
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Greeley, Colorado, United States, 80631
      • Banner North Colorado Medical Center
    • Lakewood, Colorado, United States, 80228
      • CommonSpirit Saint Anthony Hospital Cancer Center
    • Littleton, Colorado, United States, 80120
      • Rocky Mountain Cancer Centers-Littleton
    • Littleton, Colorado, United States, 80122
      • AdventHealth Littleton
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Loveland, Colorado, United States, 80539
      • Banner North Colorado Medical Center - Loveland Campus
    • Parker, Colorado, United States, 80138
      • Rocky Mountain Cancer Centers-Parker
    • Parker, Colorado, United States, 80138
      • AdventHealth Parker
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
    • Wheat Ridge, Colorado, United States, 80401
      • Intermountain Health Lutheran Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19713
      • Delaware Clinical and Laboratory Physicians PA
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Rehoboth Beach, Delaware, United States, 19971
      • Beebe Health Campus
    • Seaford, Delaware, United States, 19973
      • TidalHealth Nanticoke / Allen Cancer Center
    • Wilmington, Delaware, United States, 19801
      • Christiana Care Health System-Wilmington Hospital
  • Georgia
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush-Copley Medical Center
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Bloomington, Illinois, United States, 61701
      • OSF Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Centralia, Illinois, United States, 62801
      • Centralia Oncology Clinic
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Danville, Illinois, United States, 61832
      • Carle at The Riverfront
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Illinois - Decatur
    • Decatur, Illinois, United States, 62526
      • Heartland Cancer Research NCORP
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
    • Highland Park, Illinois, United States, 60035
      • Hematology Oncology Associates of Illinois-Highland Park
    • Libertyville, Illinois, United States, 60048
      • AMG Libertyville - Oncology
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • Moline, Illinois, United States, 61265
      • Garneau, Stewart C MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Porubcin, Michael MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Spector, David MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Trinity Medical Center
    • Monmouth, Illinois, United States, 61462
      • Illinois CancerCare-Monmouth
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists-Niles
    • Normal, Illinois, United States, 61761
      • Carle Cancer Institute Normal
    • O'Fallon, Illinois, United States, 62269
      • Cancer Care Center of O'Fallon
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Ottawa, Illinois, United States, 61350
      • Ottawa Regional Hospital and Healthcare Center
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61615
      • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Rockford, Illinois, United States, 61104
      • Swedish American Hospital
    • Rockford, Illinois, United States, 61114
      • UW Health Carbone Cancer Center Rockford
    • Skokie, Illinois, United States, 60076
      • Hematology Oncology Associates of Illinois - Skokie
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
    • Springfield, Illinois, United States, 62702
      • Central Illinois Hematology Oncology Center
    • Springfield, Illinois, United States, 62781
      • Springfield Memorial Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • The Carle Foundation Hospital
    • Yorkville, Illinois, United States, 60560
      • Rush-Copley Healthcare Center
  • Indiana
    • Indianapolis, Indiana, United States, 46219
      • IU Health Central Indiana Cancer Centers-East
    • Michigan City, Indiana, United States, 46360
      • Franciscan Saint Anthony Health-Michigan City
    • Michigan City, Indiana, United States, 46360
      • Woodland Cancer Care Center
  • Iowa
    • Ames, Iowa, United States, 50010
      • Mary Greeley Medical Center
    • Ames, Iowa, United States, 50010
      • McFarland Clinic - Ames
    • Bettendorf, Iowa, United States, 52722
      • Constantinou, Costas L MD (UIA Investigator)
    • Boone, Iowa, United States, 50036
      • McFarland Clinic - Boone
    • Clive, Iowa, United States, 50325
      • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50309
      • Iowa-Wide Oncology Research Coalition NCORP
    • Des Moines, Iowa, United States, 50309
      • UI Health Care Mission Cancer and Blood - Des Moines Clinic
    • Des Moines, Iowa, United States, 50314
      • UI Health Care Mission Cancer and Blood - Laurel Clinic
    • Fort Dodge, Iowa, United States, 50501
      • McFarland Clinic - Trinity Cancer Center
    • Jefferson, Iowa, United States, 50129
      • McFarland Clinic - Jefferson
    • Marshalltown, Iowa, United States, 50158
      • McFarland Clinic - Marshalltown
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51102
      • Mercy Medical Center-Sioux City
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical Center
    • West Des Moines, Iowa, United States, 50266-7700
      • Methodist West Hospital
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67905
      • Cancer Center of Kansas-Liberal
    • Manhattan, Kansas, United States, 66502
      • Cancer Center of Kansas-Manhattan
    • McPherson, Kansas, United States, 67460
      • Cancer Center of Kansas - McPherson
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Wichita NCI Community Oncology Research Program
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Ochsner Health Center-Summa
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
    • New Orleans, Louisiana, United States, 70115
      • Ochsner Baptist Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Elkton, Maryland, United States, 21921
      • Christiana Care - Union Hospital
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Bixby Medical Center
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium NCORP
    • Ann Arbor, Michigan, United States, 48106
      • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
    • Dearborn, Michigan, United States, 48124
      • Corewell Health Dearborn Hospital
    • Detroit, Michigan, United States, 48236
      • Henry Ford Health Saint John Hospital
    • Escanaba, Michigan, United States, 49829
      • OSF Saint Francis Hospital and Medical Group
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Lansing, Michigan, United States, 48912
      • University of Michigan Health - Sparrow Lansing
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital
    • Monroe, Michigan, United States, 48162
      • Toledo Clinic Cancer Centers-Monroe
    • Port Huron, Michigan, United States, 48060
      • Lake Huron Medical Center
    • Saginaw, Michigan, United States, 48601
      • MyMichigan Medical Center Saginaw
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55454
      • Health Partners Inc
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro Minnesota Community Oncology Research Consortium
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
  • Missouri
    • Bonne Terre, Missouri, United States, 63628
      • Parkland Health Center-Bonne Terre
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Mercy Cancer Center - Cape Girardeau
    • Jefferson City, Missouri, United States, 65109
      • MU Health Care Goldschmidt Cancer Center
    • Sainte Genevieve, Missouri, United States, 63670
      • Sainte Genevieve County Memorial Hospital
    • St Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Sullivan, Missouri, United States, 63080
      • Missouri Baptist Sullivan Hospital
    • Sunset Hills, Missouri, United States, 63127
      • BJC Outpatient Center at Sunset Hills
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Nebraska Hematology and Oncology
    • Lincoln, Nebraska, United States, 68510
      • Nebraska Cancer Research Center
    • Lincoln, Nebraska, United States, 68516
      • Cancer Partners of Nebraska
    • Omaha, Nebraska, United States, 68124
      • Alegent Health Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
    • Omaha, Nebraska, United States, 68130
      • Alegent Health Lakeside Hospital
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68106
      • Missouri Valley Cancer Consortium
    • Omaha, Nebraska, United States, 68124
      • Nebraska Cancer Specialists - Omaha
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West PC
    • Scottsbluff, Nebraska, United States, 69361
      • Regional West Medical Center Cancer Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • East Orange, New Jersey, United States, 07018-1095
      • Veterans Adminstration New Jersey Health Care System
    • Flemington, New Jersey, United States, 08822
      • Hunterdon Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology PC - Albany Medical Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health System - Akron Campus
    • Belpre, Ohio, United States, 45714
      • Strecker Cancer Center-Belpre
    • Bowling Green, Ohio, United States, 43402
      • Toledo Clinic Cancer Centers-Bowling Green
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43219
      • The Mark H Zangmeister Center
    • Columbus, Ohio, United States, 43214
      • Columbus Oncology and Hematology Associates Inc
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Columbus, Ohio, United States, 43215
      • Columbus NCI Community Oncology Research Program
    • Delaware, Ohio, United States, 43015
      • Delaware Health Center-Grady Cancer Center
    • Delaware, Ohio, United States, 43015
      • Delaware Radiation Oncology
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lancaster, Ohio, United States, 43130
      • Lancaster Radiation Oncology
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Maumee, Ohio, United States, 43537
      • Toledo Clinic Cancer Centers-Maumee
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Newark, Ohio, United States, 43055
      • Newark Radiation Oncology
    • Oregon, Ohio, United States, 43616
      • Saint Charles Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic Cancer Centers-Oregon
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Medical Center
    • Springfield, Ohio, United States, 45504
      • Springfield Regional Medical Center
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43606
      • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
    • Toledo, Ohio, United States, 43623
      • Mercy Health - Saint Anne Hospital
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Centers-Toledo
    • Toledo, Ohio, United States, 43614
      • University of Toledo
    • Toledo, Ohio, United States, 43617
      • Toledo Community Hospital Oncology Program CCOP
    • Toledo, Ohio, United States, 43608
      • Mercy Health - Saint Vincent Hospital
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System Cancer Care Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at Saint Francis
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • Lewisburg, Pennsylvania, United States, 17837
      • Geisinger Medical Oncology-Lewisburg
    • Lewistown, Pennsylvania, United States, 17044
      • Lewistown Hospital
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
    • Pottsville, Pennsylvania, United States, 17901
      • Geisinger Cancer Services-Pottsville
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Medical Center
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology Inc
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Charleston Division
  • Wisconsin
    • Burlington, Wisconsin, United States, 53105
      • Aurora Cancer Care-Southern Lakes VLCC
    • Fond du Lac, Wisconsin, United States, 54937
      • Aurora Health Center-Fond du Lac
    • Germantown, Wisconsin, United States, 53022
      • Aurora Health Care Germantown Health Center
    • Grafton, Wisconsin, United States, 53024
      • Aurora Cancer Care-Grafton
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay, Wisconsin, United States, 54303
      • Saint Vincent Hospital Cancer Center at Saint Mary's
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology at Saint Vincent Hospital
    • Johnson Creek, Wisconsin, United States, 53038
      • University of Wisconsin Carbone Cancer Center - Johnson Creek
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center - University Hospital
    • Manitowoc, Wisconsin, United States, 54221
      • Holy Family Memorial Hospital
    • Marinette, Wisconsin, United States, 54143
      • Aurora Bay Area Medical Group-Marinette
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Aurora Cancer Care-Milwaukee
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Sinai Medical Center
    • Milwaukee, Wisconsin, United States, 53210
      • Ascension Southeast Wisconsin Hospital - Saint Joseph Campus
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin
    • Oconto Falls, Wisconsin, United States, 54154
      • Saint Vincent Hospital Cancer Center at Oconto Falls
    • Oshkosh, Wisconsin, United States, 54904
      • Vince Lombardi Cancer Clinic - Oshkosh
    • Racine, Wisconsin, United States, 53406
      • Aurora Cancer Care-Racine
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • Sheboygan, Wisconsin, United States, 53081
      • HSHS Saint Nicholas Hospital
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic-Two Rivers
    • Waukesha, Wisconsin, United States, 53188
      • Aurora Cancer Care-Waukesha
    • Wauwatosa, Wisconsin, United States, 53226
      • Aurora Cancer Care-Milwaukee West
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have unresectable stage III or stage IV melanoma, either initial presentation or recurrent, that is of cutaneous origin or unknown primary origin and that is histologically diagnosed
• No more than one prior systemic therapeutic regimen for unresectable stage III or stage IV melanoma; this includes chemotherapy, biologic therapy, biochemotherapy, or investigational treatment; this does not include any therapies given in the adjuvant setting; however, patients are excluded if they have a history of prior treatment for melanoma (either adjuvant or metastatic disease) with ipilimumab or other cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor, or prior interferon-alpha treatment for metastatic disease (history of adjuvant interferon-alpha is allowed); there should be a 4-week washout period between last treatment administration and initiation of study therapy
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Patients must not have other significant medical, surgical, or psychiatric conditions or require any medication or treatment that in the opinion of the investigator may interfere with compliance, make the administration of ipilimumab or HDI hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea; patients must not have an active infection requiring current treatment with parenteral antibiotics
• Patients must not have a history of inflammatory bowel disease or diverticulitis (history of diverticulosis is allowed)

• Patients who have other current malignancies are not eligible; patients with other malignancies are eligible if they have been continuously disease free for > 5 years prior to the time of randomization; one exception are patients treated with a curative intent and are continuously disease free for > 3 years; these patients would be considered eligible:

  • Patients with prior history at any time of any in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or Clark I melanoma in situ are eligible
  • Patients with prior history of basal or squamous skin cancer are eligible
• Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (e.g., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed; replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of these classes of medication for at least 2 weeks prior to randomization are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study; exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis [e.g., Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and Myasthenia gravis); other central nervous system (CNS) autoimmune disease (e.g., poliomyelitis, multiple sclerosis); patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible
• Due to the possible effect of treatment with ipilimumab on the immunologic response to infectious disease vaccines, patients must not have had any infectious disease vaccination (e.g, standard influenza, H1N1 influenza, pneumococcal, meningococcal, tetanus toxoid) within 4 weeks prior to randomization

• Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study during screening to rule out pregnancy; NOTE: a woman of childbearing potential (WOCBP) is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); for the purposes of this study, post-menopause is defined as:

  • Amenorrhea >= 24 consecutive months without another cause, or
  • For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >= 35 mIU/mL Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential; men of fathering potential and WOCBP must be using an adequate method of contraception or must abstain from sexual intercourse to avoid conception/pregnancy throughout the study and for up to 26 weeks after the last dose of ipilimumab or HDI in such a manner that the risk of pregnancy is minimized; men or WOCBP who are unwilling or unable to strictly follow this requirement are not eligible
• White blood cells (WBC) >= 3000/uL
• Absolute neutrophil count (ANC) >= 1500/uL
• Platelets >= 100 x 10^3/uL
• Hemoglobin >= 10 g/dL
• Serum creatinine =< 1.8 mg/dl
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) for patients with liver metastases and =< 2.0 x ULN for patients without liver metastases
• Serum bilirubin < 2 x ULN for patients with liver metastases and =< 1.5 x ULN for patients without liver metastases, (except patients with Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL)
• No active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Patients must be free of brain metastasis by contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI) scans within 4 weeks prior to enrollment; if known to have prior brain metastases, must not have evidence of active brain disease after definitive therapy (surgery, radiation therapy or stereotactic radiosurgery) on two successive MRI evaluations at least 3 months apart (one of which is =< 4 weeks prior to starting the study drugs)
• All sites of disease must be evaluated within 4 weeks prior to randomization; patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (higher dose ipilimumab, HDI); INDUCTION PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses and recombinant interferon alfa-2b IV over 20 minutes 5 days a week for 4 weeks and then SC 3 times weekly for 8 weeks. MAINTENANCE PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24 and recombinant interferon alfa-2b SC 3 times weekly for 48 weeks.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Ipilimumab; Given IV; Other Names: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody; BMS-734016; Ipilimumab Biosimilar CS1002; MDX-010; MDX-CTLA4; Yervoy; MDX010; BMS734016; BMS 734016; MDX 010; Biological: Recombinant Interferon Alfa-2b; Given IV or SC; Other Names: Alfatronol; Glucoferon; Heberon Alfa; IFN alpha-2B; Interferon alfa 2b; Interferon Alfa-2B; Interferon Alpha-2b; Intron A; Sch 30500; Urifron; Viraferon; Bioferon; Bioferon (TM)
Experimental: Arm B (higher dose ipilimumab); INDUCTION PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses. MAINTENANCE PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Ipilimumab; Given IV; Other Names: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody; BMS-734016; Ipilimumab Biosimilar CS1002; MDX-010; MDX-CTLA4; Yervoy; MDX010; BMS734016; BMS 734016; MDX 010
Experimental: Arm C (lower dose ipilimumab + HDI); INDUCTION PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses and recombinant interferon alfa-2b IV over 20 minutes 5 days a week for 4 weeks and then SC 3 times weekly for 8 weeks. MAINTENANCE PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24 and recombinant interferon alfa-2b SC 3 times weekly for 48 weeks.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Ipilimumab; Given IV; Other Names: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody; BMS-734016; Ipilimumab Biosimilar CS1002; MDX-010; MDX-CTLA4; Yervoy; MDX010; BMS734016; BMS 734016; MDX 010; Biological: Recombinant Interferon Alfa-2b; Given IV or SC; Other Names: Alfatronol; Glucoferon; Heberon Alfa; IFN alpha-2B; Interferon alfa 2b; Interferon Alfa-2B; Interferon Alpha-2b; Intron A; Sch 30500; Urifron; Viraferon; Bioferon; Bioferon (TM)
Experimental: Arm D (lower dose ipilimumab); INDUCTION PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses. MAINTENANCE PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Ipilimumab; Given IV; Other Names: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody; BMS-734016; Ipilimumab Biosimilar CS1002; MDX-010; MDX-CTLA4; Yervoy; MDX010; BMS734016; BMS 734016; MDX 010

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Progression-free survival (PFS) was defined as time from randomization to any documented disease progression or death from any cause, whichever occurred first (event), or censored at last date known alive.	Assessed every 3 months for two years, then every 6 months for 3 years, then every 12 months for up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival (PFS) was defined as time from randomization to any documented disease progression or death from any cause, whichever occurred first (event), or censored at last date known alive.	Assessed every 3 months for two years, then every 6 months for 3 years, then every 12 months for up to 10 years
Overall Survival (OS)	Time from randomization to death (event), or censored at last date known alive	Assessed every 3 months for two years, then every 6 months for 3 years, then every 12 months for up to 10 years
Overall Survival	Time from randomization to death (event), or censored at last date known alive.	Assessed every 3 months for two years, then every 6 months for 3 years, then every 12 months for up to 10 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response Rate	Defined as the number of complete responses and partial responses per RECIST version 1.1 divided by the total number of evaluable cases	Assessed every 12 weeks for 3 years
Immune-related Response Rate Per Immune-related Response Criteria	Defined as the number of complete and partial responses per immune-related response criteria (irRC) divided by the total number of evaluable patients	Assessed every 12 weeks for 3 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ahmad Tarhini, ECOG-ACRIN Cancer Research Group

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2013
• Primary Completion (Actual): August 8, 2017
• Study Completion (Estimated): March 17, 2027

Study Registration Dates

• First Submitted: October 15, 2012
• First Submitted That Met QC Criteria: October 15, 2012
• First Posted (Estimated): October 17, 2012

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Receptors, Cell Surface; Membrane Proteins; Intercellular Signaling Peptides and Proteins; Cytokines; Interferon Type I; Interferons; Interferon-alpha; Antigens; Antigens, Surface; Biomarkers; Gene Components; Genes; Receptors, Immunologic; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; DNA, Intergenic; Interferon alpha-2; Ipilimumab; CTLA-4 Antigen; Introns
• Other Study ID Numbers: NCI-2012-01932 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180820 (U.S. NIH Grant/Contract); U24CA196172 (U.S. NIH Grant/Contract); U10CA021115 (U.S. NIH Grant/Contract); CDR0000741878; ECOG-E3611; E3611 (Other Identifier: CTEP)