Ipilimumab With or Without Sargramostim in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
Advanced Melanoma, Metastatic Melanoma, Recurrent Melanoma
About this trial
This is an interventional treatment trial for Advanced Melanoma
Eligibility Criteria
Inclusion Criteria:
- 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)
- 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
- Histologic diagnosis of metastatic melanoma; for unknown primary disease, diagnosis of metastatic disease by cytology fine needle aspiration (FNA) is not acceptable
- Women must not be pregnant or breast-feeding due to unknown effects of ipilimumab and GM-CSF on the unborn fetus; all women of childbearing potential must have a blood test within 72 hours prior to randomization to rule out pregnancy; women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception; women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized; sexually mature females who have not undergone a hysterectomy or who have not been postmenopausal naturally for at least 24 consecutive months (i.e., who have had menses at some time in the preceding 24 consecutive months) are considered to be of childbearing potential; 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
- White blood cells (WBC) >= 2000/uL (obtained =< 4 weeks prior to randomization)
- Absolute neutrophil count (ANC) >= 1500/mcL (obtained =< 4 weeks prior to randomization)
- Platelets >= 100,000/mcL (obtained =< 4 weeks prior to randomization)
- Hemoglobin >= 8 g/dL (obtained =< 4 weeks prior to randomization)
- Creatinine =< 3.0 x upper limit of normal (ULN) (obtained =< 4 weeks prior to randomization)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (obtained =< 4 weeks prior to randomization)
- Bilirubin =< 3.0 x ULN, (except patients with Gilbert's syndrome, who must have a total bilirubin less than 3.0 mg/dL) (obtained =< 4 weeks prior to randomization)
- No concomitant therapy with any of the following: interleukin (IL) 2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids; must have been discontinued >= 4 weeks
- No infection with human immunodeficiency virus (HIV); due to the mechanism of action of ipilimumab and GM-CSF, activity and side effects in an immune compromised patient are unknown
- No active infection with hepatitis B
- No active or chronic infection with hepatitis C
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Exclusion Criteria:
- Patients with any history of central nervous system (CNS) metastases are excluded
- Patients are excluded if they have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix
- Patients are excluded if they have a history of any autoimmune disease; patients with a history of autoimmune thyroiditis are eligible if their current thyroid disorder is treated and stable with replacement or other medical therapy
- Patients are excluded for any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea
- Patients are excluded for receiving any non-oncology vaccine therapy used for prevention of infectious diseases for up to four weeks (28 days) prior to or after any dose of ipilimumab
- Patients are excluded if they have a history of prior treatment with ipilimumab or prior cluster of differentiation (CD)137 agonist or cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor or agonist
- Any concurrent medical condition requiring the use of systemic steroids is not permitted (the use of inhaled or topical steroids is permitted)
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- Stanford Cancer Institute Palo Alto
- VA Palo Alto Health Care System
- Eisenhower Medical Center
- The Medical Center of Aurora
- Boulder Community Hospital
- Penrose-Saint Francis Healthcare
- Porter Adventist Hospital
- Presbyterian - Saint Lukes Medical Center - Health One
- SCL Health Saint Joseph Hospital
- Rose Medical Center
- Western States Cancer Research NCORP
- Swedish Medical Center
- Poudre Valley Hospital
- Saint Mary's Hospital and Regional Medical Center
- North Colorado Medical Center
- Saint Anthony Hospital
- Sky Ridge Medical Center
- Longmont United Hospital
- McKee Medical Center
- Saint Mary Corwin Medical Center
- North Suburban Medical Center
- SCL Health Lutheran Medical Center
- Smilow Cancer Hospital Care Center at Saint Francis
- Manchester Memorial Hospital
- The Hospital of Central Connecticut
- Yale University
- Eastern Connecticut Hematology and Oncology Associates
- Beebe Medical Center
- Christiana Care Health System-Christiana Hospital
- Boca Raton Regional Hospital
- Lakeland Regional Health Hollis Cancer Center
- 21st Century Oncology-Orange Park
- University Cancer and Blood Center LLC
- Emory University Hospital/Winship Cancer Institute
- Augusta University Medical Center
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Rush - Copley Medical Center
- MacNeal Hospital and Cancer Center
- Saint Joseph Medical Center
- Graham Hospital Association
- Memorial Hospital
- Hematology and Oncology Associates
- Northwestern University
- Rush University Medical Center
- Decatur Memorial Hospital
- Heartland Cancer Research NCORP
- Eureka Hospital
- Illinois CancerCare-Galesburg
- Mason District Hospital
- Hematology Oncology Associates of Illinois-Highland Park
- Hinsdale Hematology Oncology Associates Incorporated
- Duly Health and Care Joliet
- Presence Saint Mary's Hospital
- AMG Libertyville - Oncology
- Mcdonough District Hospital
- Trinity Medical Center
- DuPage Medical Group-Ogden
- Illinois Cancer Specialists-Niles
- Bromenn Regional Medical Center
- Carle Cancer Institute Normal
- Ottawa Regional Hospital and Healthcare Center
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Proctor Hospital
- Illinois CancerCare-Peoria
- Methodist Medical Center of Illinois
- OSF Saint Francis Medical Center
- Illinois Valley Hospital
- Perry Memorial Hospital
- Swedish American Hospital
- SwedishAmerican Regional Cancer Center/ACT
- Hematology Oncology Associates of Illinois - Skokie
- Memorial Medical Center
- Carle Cancer Center
- Elkhart General Hospital
- Indiana University/Melvin and Bren Simon Cancer Center
- Community Howard Regional Health
- IU Health La Porte Hospital
- Franciscan Saint Anthony Health-Michigan City
- Saint Joseph Regional Medical Center-Mishawaka
- IU Health Ball Memorial Hospital
- Memorial Hospital of South Bend
- Northern Indiana Cancer Research Consortium
- McFarland Clinic - Ames
- Mercy Hospital
- Oncology Associates at Mercy Medical Center
- Medical Oncology and Hematology Associates-West Des Moines
- Iowa Methodist Medical Center
- Iowa-Wide Oncology Research Coalition NCORP
- Medical Oncology and Hematology Associates-Des Moines
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- Mercy Medical Center - North Iowa
- Siouxland Regional Cancer Center
- Mercy Medical Center-Sioux City
- Saint Luke's Regional Medical Center
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas - El Dorado
- Cancer Center of Kansas-Kingman
- Lawrence Memorial Hospital
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas - Newton
- Cancer Center of Kansas - Parsons
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Cancer Center of Kansas - Wellington
- Associates In Womens Health
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Ascension Via Christi Hospitals Wichita
- Cancer Center of Kansas - Wichita
- Wichita NCI Community Oncology Research Program
- Cancer Center of Kansas - Winfield
- Owensboro Health Mitchell Memorial Cancer Center
- Ochsner Health Center-Summa
- Ochsner Health Center-Covington
- Ochsner Medical Center Jefferson
- Greater Baltimore Medical Center
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Christiana Care - Union Hospital
- Massachusetts General Hospital Cancer Center
- Beth Israel Deaconess Medical Center
- Dana-Farber Cancer Institute
- Baystate Medical Center
- Michigan Cancer Research Consortium NCORP
- Saint Joseph Mercy Hospital
- Beaumont Hospital - Dearborn
- Ascension Saint John Hospital
- Hurley Medical Center
- Genesys Regional Medical Center-West Flint Campus
- Allegiance Health
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Borgess Medical Center
- Sparrow Hospital
- Trinity Health Saint Mary Mercy Livonia Hospital
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- Ascension Saint Mary's Hospital
- Lakeland Medical Center Saint Joseph
- Marie Yeager Cancer Center
- Saint John Macomb-Oakland Hospital
- Fairview Ridges Hospital
- Mercy Hospital
- Essentia Health Cancer Center
- Essentia Health Saint Mary's Medical Center
- Miller-Dwan Hospital
- Fairview Southdale Hospital
- Unity Hospital
- Hutchinson Area Health Care
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- North Memorial Medical Health Center
- Metro Minnesota Community Oncology Research Consortium
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Nebraska Cancer Research Center
- Alegent Health Immanuel Medical Center
- Alegent Health Bergan Mercy Medical Center
- Creighton University Medical Center
- Nevada Cancer Institute-Summerlin Campus
- Nevada Cancer Research Foundation NCORP
- Cooper Hospital University Medical Center
- Hunterdon Medical Center
- Hackensack University Medical Center
- Morristown Medical Center
- Virtua Memorial
- Rutgers Cancer Institute of New Jersey
- Overlook Hospital
- University of New Mexico Cancer Center
- Presbyterian Kaseman Hospital
- San Juan Oncology Associates
- New York Oncology Hematology PC - Albany Medical Center
- Mary Imogene Bassett Hospital
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Stony Brook University Medical Center
- Sanford Broadway Medical Center
- Summa Health System - Akron Campus
- Cleveland Clinic Mercy Hospital
- Aultman Health Foundation
- The Christ Hospital
- Case Western Reserve University
- MetroHealth Medical Center
- Cleveland Clinic Foundation
- Saint Rita's Medical Center
- Saint Charles Hospital
- ProMedica Flower Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- Saint Vincent Mercy Medical Center
- Jefferson Abington Hospital
- Lehigh Valley Hospital-Cedar Crest
- Saint Luke's University Hospital-Bethlehem Campus
- Bryn Mawr Hospital
- Geisinger Medical Center
- Doylestown Hospital
- Geisinger Medical Center-Cancer Center Hazleton
- Saint Mary Medical and Regional Cancer Center
- Paoli Memorial Hospital
- Thomas Jefferson University Hospital
- University of Pittsburgh Cancer Institute (UPCI)
- Pottstown Hospital
- Guthrie Medical Group PC-Robert Packer Hospital
- Hematology and Oncology Associates of North East Pennsylvania
- Reading Hospital
- Geisinger Wyoming Valley/Henry Cancer Center
- Lankenau Medical Center
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Medical X-Ray Center
- Avera McKennan Hospital and University Health Center
- Sanford USD Medical Center - Sioux Falls
- Erlanger Medical Center
- Jackson-Madison County General Hospital
- Vanderbilt University/Ingram Cancer Center
- Parkland Memorial Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- University of Virginia Cancer Center
- West Virginia University Charleston Division
- West Virginia University Healthcare
- Wheeling Hospital/Schiffler Cancer Center
- Langlade Hospital and Cancer Center
- ThedaCare Regional Cancer Center
- Marshfield Clinic-Chippewa Center
- Marshfield Clinic Cancer Center at Sacred Heart
- Saint Vincent Hospital Cancer Center Green Bay
- Aurora BayCare Medical Center
- Mercyhealth Hospital and Cancer Center - Janesville
- UW Cancer Center Johnson Creek
- Gundersen Lutheran Medical Center
- Dean Hematology and Oncology Clinic
- University of Wisconsin Carbone Cancer Center
- Holy Family Memorial Hospital
- Aurora Bay Area Medical Group-Marinette
- Bay Area Medical Center
- Marshfield Medical Center-Marshfield
- Marshfield Clinic-Minocqua Center
- ProHealth Oconomowoc Memorial Hospital
- Ascension Saint Mary's Hospital
- Marshfield Medical Center-Rice Lake
- HSHS Saint Nicholas Hospital
- Vince Lombardi Cancer Clinic-Sheboygan
- Ascension Saint Michael's Hospital
- Aurora Medical Center in Summit
- Vince Lombardi Cancer Clinic-Two Rivers
- ProHealth Waukesha Memorial Hospital
- Aspirus Regional Cancer Center
- Marshfield Clinic-Wausau Center
- Marshfield Medical Center - Weston
- Marshfield Clinic - Wisconsin Rapids Center
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm A (ipilimumab and sargramostim)
Arm B (ipilimumab)
Patients receive induction therapy comprising ipilimumab IV over 90 minutes on day 1 and sargramostim SC once daily on days 1-14. Treatment repeats every 21 days for 4 cycles. After 12 weeks of induction treatment, anti-tumor response is assessed and patients then receive maintenance therapy comprising ipilimumab IV over 90 minutes on day 1 and sargramostim SC once daily on days 1-14. Treatment with ipilimumab repeats every 12 weeks and treatment with sargramostim repeats every 21 days. After 12 weeks of maintenance therapy, anti-tumor response is reassessed and patients with responsive or stable disease then continue maintenance therapy until disease progression or unacceptable toxicity.
Patients receive induction therapy comprising ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles. After 12 weeks of induction treatment, anti-tumor response is assessed and patients then receive maintenance therapy of ipilimumab IV over 90 minutes on day 1. Treatment with ipilimumab repeats every 12 weeks. After 12 weeks of maintenance therapy, anti-tumor response is reassessed and cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity