Sargramostim, Vaccine Therapy, or Sargramostim and Vaccine Therapy in Preventing Disease Recurrence in Patients With Melanoma That Has Been Removed By Surgery

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01989572
• Collaborator: (none)
• Enrollment: 815
• Locations: 148
• Arms: 6
• Actual Duration (Months): 155.3
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase III trial studies sargramostim or vaccine therapy alone to see how well they work compared to sargramostim and vaccine therapy together in preventing disease recurrence in patients with melanoma that has been removed by surgery. Sargramostim may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. It is not yet known whether yeast derived sargramostim and vaccine therapy are more effective alone or together in preventing recurrence of melanoma.

Condition or Disease	Intervention/Treatment	Phase
Iris Melanoma; Medium/Large Size Posterior Uveal Melanoma; Mucosal Melanoma; Ocular Melanoma With Extraocular Extension; Recurrent Melanoma; Recurrent Uveal Melanoma; Small Size Posterior Uveal Melanoma; Stage IIA Cutaneous Melanoma AJCC v6 and v7; Stage IIA Uveal Melanoma AJCC v7; Stage IIB Cutaneous Melanoma AJCC v6 and v7; Stage IIB Uveal Melanoma AJCC v7; Stage IIC Cutaneous Melanoma AJCC v6 and v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIA Uveal Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIB Uveal Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IIIC Uveal Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Uveal Melanoma AJCC v7	Other: Laboratory Biomarker Analysis; Other: Placebo; Other: Placebo; Biological: Sargramostim; Biological: Tyrosinase Peptide	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To compare overall survival and disease-free survival of patients with completely resected stage IV melanoma or stage III melanoma with gross extranodal extension, satellites, and/or intransit lesions, treated with granulocyte macrophage colony-stimulating factor (GM-CSF) (sargramostim) vs. no GM-CSF, or other high risk patients listed in the eligibility section.

SECONDARY OBJECTIVES:

1. To compare, using a 2 x 2 factorial design, overall survival and disease-free survival of human leukocyte antigen (HLA)-A2 positive patients treated with peptide vaccination vs. no peptide vaccination.

2. The following descriptive evaluations of survival and disease-free survival are planned for the HLA-A2 positive patients: (1) GM-CSF plus peptide vaccination vs. peptide vaccination alone; (2) GM-CSF plus peptide vaccination vs. GM-CSF alone; (3) GM-CSF plus peptide vaccination vs. placebo.

3. Survival and disease-free survival of HLA-A2 positive patients not receiving peptide vaccination will be compared to that of HLA-A2 negative patients not receiving peptide vaccination.

4. To determine the influence of GM-CSF on circulating dendritic cell numbers and subpopulations in peripheral blood of patients receiving and not receiving GM-CSF.

5. To determine, in HLA-A2 positive patients, whether immunization with peptides with or without GM-CSF elicits a measurable T-cell response as assessed by enzyme-linked immunosorbent spot (ELISPOT) and the major histocompatibility complex (MHC) tetramer assay, and to determine the functionality of these cells by intracellular cytokine staining.

OUTLINE: HLA-A2 positive patients are randomized to 1 of 4 treatment regimens (Arms I-IV). HLA-A2 negative patients are randomized to 1 of 2 treatment arms (Arms V-VI).

ARM I: Patients receive sargramostim subcutaneously (SC) on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses).

ARM II: Patients receive sargramostim placebo SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses).

ARM III: Patients receive sargramostim SC on days 1-14 and peptide placebo mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses).

ARM IV: Patients receive sargramostim placebo SC on days 1-14 and peptide placebo mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses).

ARM V: Patients receive sargramostim SC on days 1-14.

ARM VI: Patients receive sargramostim placebo SC on days 1-14.

In all arms, treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

In the event of recurrence, patients who undergo complete resection of the recurrence may continue treatment for 6 courses or until completion of 1 year of therapy (whichever is longer). For patients with recurrence that is not surgically resectable or experiencing second recurrence, treatment will be discontinued.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 10 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 815 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Randomized, Placebo-Controlled Phase III Trial of Yeast Derived GM-CSF Versus Peptide Vaccination Versus GM-CSF Plus Peptide Vaccination Versus Placebo in Patients With "No Evidence of Disease" After Complete Surgical Resection of "Locally Advanced" and/or Stage IV Melanoma
• Actual Study Start Date: Feb 23, 2000
• Actual Primary Completion Date: Oct 8, 2012
• Actual Study Completion Date: Jan 31, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (sargramostim, peptide vaccine) Patients receive sargramostim SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses).	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Sargramostim; Given SC; Other Names: 23-L-Leucinecolony-Stimulating Factor 2 DRG-0012 Leukine Prokine rhu GM-CFS Sagramostim Sargramostatin ; Biological: Tyrosinase Peptide; Given SC; Other Names: Tyrosinase Peptides
Experimental: Arm II (sargramostim placebo, peptide vaccine) Patients receive sargramostim placebo SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses).	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo; Given GM-CSF placebo SC; Other Names: placebo therapy PLCB sham therapy ; Biological: Tyrosinase Peptide; Given SC; Other Names: Tyrosinase Peptides
Experimental: Arm III (sargramostim, peptide placebo) Patients receive sargramostim SC on days 1-14 and peptide placebo mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses).	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo; Given peptide placebo SC; Other Names: placebo therapy PLCB sham therapy ; Biological: Sargramostim; Given SC; Other Names: 23-L-Leucinecolony-Stimulating Factor 2 DRG-0012 Leukine Prokine rhu GM-CFS Sagramostim Sargramostatin
Placebo Comparator: Arm IV (placebo, peptide placebo) Patients receive placebo SC on days 1-14 and peptide placebo on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses).	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo; Given GM-CSF placebo SC; Other Names: placebo therapy PLCB sham therapy ; Other: Placebo; Given peptide placebo SC; Other Names: placebo therapy PLCB sham therapy
Experimental: Arm V (sargramostim) Patients receive sargramostim SC on days 1-14.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Sargramostim; Given SC; Other Names: 23-L-Leucinecolony-Stimulating Factor 2 DRG-0012 Leukine Prokine rhu GM-CFS Sagramostim Sargramostatin
Placebo Comparator: Arm VI (sargramostim placebo) Patients receive sargramostim placebo SC on days 1-14.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo; Given GM-CSF placebo SC; Other Names: placebo therapy PLCB sham therapy

Outcome Measures

Primary Outcome Measures

1. Overall Survival [assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry, and annually if >5 years, up to year 15]

   Overall survival is defined as time from randomization to death from any cause.

2. Recurrence Free Survival [assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry, and annually if >5 years, up to year 15]

   Recurrence free survival is defined as time from randomization to first disease recurrence or death from any cause (whichever occur first), censoring cases without recurrence or death at the last date of known free of recurrence free survival events. Disease recurrence was determined based on positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease, or a positive brain CT or MRI scan or CSF cytology.

Secondary Outcome Measures

1. Overall Survival in Human Leukocyte Antigens-A2 (HLA-A2) Positive Patients [assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry, and annually if >5 years,up to year 15]

   Overall survival is defined as time from randomization to death from any cause.

2. Recurrence Free Survival in HLA-A2 Positive Patients [assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry, and annually if >5 years, up to year 15]

   Recurrence free survival is defined as time from randomization to first disease recurrence or death from any cause (whichever occur first), censoring cases without recurrence or death at the last date of known free of recurrence free survival events. Disease recurrence was determined based on positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease, or a positive brain CT or MRI scan or CSF cytology.

3. 5-year Overall Survival Rate [assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry, and annually if >5 years, up to year 15]

   Overall survival is defined as time from randomization to death from any cause, and 5-year overall survival rate is estimated via Kaplan-Meier method.

4. 5-year Recurrence Free Survival Rate [assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry, and annually if >5 years, up to year 15]

   Recurrence free survival is defined as time from randomization to first disease recurrence or death from any cause (whichever occur first), censoring cases without recurrence or death at the last date of known free of recurrence free survival events, and 5-year overall survival rate is estimated via Kaplan-Meier method. Disease recurrence was determined based on positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease, or a positive brain CT or MRI scan or CSF cytology.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have HLA-A2 status known prior to randomization; typing may be obtained through a local laboratory facility or through a reference lab utilized by the initiating institution; if typing is not available through these means, it may be obtained from the University of Pittsburgh

• All patients must have disease completely resected with one of the following in order to be eligible:

• Completely resected disease

• Any locoregional recurrence after prior adjuvant interferon or failure on S008

• Any local recurrence of disease after adequate surgical excision of the original primary

• Mucosal melanoma

• Stage IV melanoma (cutaneous, ocular, mucosal, or unknown primary)

• The following groups of patients may be entered onto this trial only if they are ineligible for S0008 or are, in the opinion of the managing physician, medically unfit to receive standard high-dose interferon:

• Any clinically evident satellite or in-transit disease

• Stage II disease with gross extracapsular extension

• Recurrence in a previously resected nodal basin

• Four or more involved lymph nodes or matted lymph nodes

• Ulcerated primary melanoma and any involved lymph nodes

• NOTE: Patients who are eligible for S0008 will be strongly encouraged to participate in that study in preference to this one

• Patients must have been surgically rendered free of disease with negative margins on resected specimens; patients rendered free of disease by non-surgical means are not eligible

• Patients must be randomized within 112 days (16 weeks) of surgical resection; if more than one surgical procedure is required to render the patient disease-free, all required surgeries must be accomplished within this 16 week time period

• Patients must not have received any adjuvant treatment (chemotherapy, biotherapy, or limb perfusion) after the resection(s) that make(s) them eligible for this trial; one systemic treatment after a prior surgery is allowed, and must have been completed >= 8 weeks prior to randomization; (when chemotherapy and biotherapy are given together as one planned treatment [biochemotherapy], this counts as one regimen); NOTE: Previous radiation therapy, including after the resection, is allowed as long as 30 days elapse between the radiation and initiation of therapy

• Prior treatment with GM-CSF or any peptides used in this protocol, is not allowed

• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Patients must not have an active infection requiring treatment with parenteral antibiotics

• Patients must not have other significant medical, surgical, or psychiatric conditions or require any medication or treatment that may interfere with compliance on any of the E4697 treatment regimens

• Patients must not have a diagnosis or evidence of organic brain syndrome or significant impairment of basal cognitive function or any psychiatric disorder that might preclude participation in the full protocol

• Patients must be able to self-administer or arrange for administration of subcutaneous injections

• Patients who have other current malignancies are not 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 who meet this criteria must be disease-free at time of randomization

• Patients with prior history of basal or squamous skin cancer are eligible; patients who meet this criteria must be disease-free at time of randomization

• Patients who have had multiple primary melanomas are eligible

• Patients with other malignancies are eligible if they have been continuously disease free for > 5 years prior to the time of randomization

• Patients must not have autoimmune disorders, conditions of immunosuppression or treatment with systemic corticosteroids, including oral steroids (i.e., prednisone, dexamethasone), continuous use of topical steroid creams or ointments, or any steroid containing inhalers; 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, the patient is not likely to require these classes of drugs during the study

• Women of childbearing potential must not be pregnant (negative beta human chorionic gonadotropin [bHCG] within 2 weeks prior to randomization) or breast-feeding

• Women of childbearing potential and sexually active males must be counseled to use an accepted and effective method of contraception (including abstinence) while on treatment and for a period of 18 months after completing or discontinuing treatment

• All patients must have brain computed tomography (CT) or magnetic resonance imaging (MRI), chest CT or chest x-ray (CXR), and abdominal (liver) CT or MRI within 4 weeks prior to randomization; positron emission tomography (PET) scans are also acceptable in place of CT, CXR and/or abdominal MRI if obtained within 4 weeks prior to randomization; patients with lesions on the lower extremity must also have pelvic imaging within this time period; this is also strongly recommended for patients with lesions on the lower trunk; PET scans are acceptable

• Patients with resection of visceral disease must have imaging of the affected area/organ documenting disease-free status within 2 weeks prior to randomization

• White blood cells (WBC) >= 3,000/mm?

• Platelet count >= 100,000/mm?

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2 x institutional upper limit (IUL) of normal

• Bilirubin =< 2 x IUL of normal

• Serum creatinine =< 1.8 mg/dl

• Alkaline phosphatase and lactate dehydrogenase (LDH) must be performed within 4 weeks prior to randomization; LDH must be normal; patients with abnormal alkaline phosphatase which is =< 1.25 times the institutional upper limit of normal who have a negative CT or MRI of the liver and negative bone scan or a negative PET scan are eligible

• Patients with bone pain must have a bone scan within 4 weeks prior to randomization to document the absence of tumor

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	Mobile Infirmary Medical Center	Mobile	Alabama	United States	36607
3	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
4	Banner University Medical Center - Tucson	Tucson	Arizona	United States	85719
5	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
6	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
7	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
8	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
9	Saint Joseph Hospital - Orange	Orange	California	United States	92868
10	Stanford Cancer Institute Palo Alto	Palo Alto	California	United States	94304
11	VA Palo Alto Health Care System	Palo Alto	California	United States	94304
12	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
13	Kaiser Permanente-San Diego Mission	San Diego	California	United States	92108
14	Naval Medical Center -San Diego	San Diego	California	United States	92134
15	Veterans Administration-San Diego Medical Center	San Diego	California	United States	92161
16	The Medical Center of Aurora	Aurora	Colorado	United States	80012
17	Boulder Community Hospital	Boulder	Colorado	United States	80301
18	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
19	Swedish Medical Center	Englewood	Colorado	United States	80113
20	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81501
21	Manchester Memorial Hospital	Manchester	Connecticut	United States	06040
22	Southwest Florida Regional Medical Center	Fort Myers	Florida	United States	33901
23	Baptist MD Anderson Cancer Center	Jacksonville	Florida	United States	32207
24	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
25	Jupiter Medical Center	Jupiter	Florida	United States	33458
26	Lakeland Regional Health Hollis Cancer Center	Lakeland	Florida	United States	33805
27	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
28	AdventHealth Orlando	Orlando	Florida	United States	32803
29	Florida Cancer Specialists-West Palm Beach	West Palm Beach	Florida	United States	33401
30	Cleveland Clinic-Weston	Weston	Florida	United States	33331
31	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	United States	30322
32	Augusta University Medical Center	Augusta	Georgia	United States	30912
33	Atlanta VA Medical Center	Decatur	Georgia	United States	30033
34	Eisenhower Army Medical Center	Fort Gordon	Georgia	United States	30905-5650
35	Medical Center of Central Georgia	Macon	Georgia	United States	31201
36	South Georgia Medical Center/Pearlman Cancer Center	Valdosta	Georgia	United States	31602
37	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
38	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
39	Northwestern University	Chicago	Illinois	United States	60611
40	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
41	Loyola University Medical Center	Maywood	Illinois	United States	60153
42	Memorial Medical Center	Springfield	Illinois	United States	62781
43	Carle Cancer Center	Urbana	Illinois	United States	61801
44	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
45	IU Health Methodist Hospital	Indianapolis	Indiana	United States	46202
46	IU Health Ball Memorial Hospital	Muncie	Indiana	United States	47303
47	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
48	Genesis Medical Center - East Campus	Davenport	Iowa	United States	52803
49	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
50	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa	United States	50309
51	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
52	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
53	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
54	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
55	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky	United States	40202
56	Ochsner Health Center-Summa	Baton Rouge	Louisiana	United States	70809
57	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
58	Eastern Maine Medical Center	Bangor	Maine	United States	04401
59	Anne Arundel Medical Center	Annapolis	Maryland	United States	21401
60	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
61	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
62	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
63	Tufts Medical Center	Boston	Massachusetts	United States	02111
64	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
65	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
66	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
67	Franklin Medical Center	Greenfield	Massachusetts	United States	01301
68	Baystate Medical Center	Springfield	Massachusetts	United States	01199
69	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
70	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
71	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
72	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
73	Mayo Clinic	Rochester	Minnesota	United States	55905
74	Hattiesburg Clinic - Hematology/Oncology Clinic	Hattiesburg	Mississippi	United States	39401
75	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
76	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri	United States	63141
77	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
78	Saint Vincent Healthcare	Billings	Montana	United States	59101
79	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
80	CHI Health Saint Francis	Grand Island	Nebraska	United States	68803
81	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
82	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
83	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
84	Creighton University Medical Center	Omaha	Nebraska	United States	68131
85	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
86	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
87	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
88	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
89	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey	United States	07018-1095
90	The Cancer Institute of New Jersey Hamilton	Hamilton	New Jersey	United States	08690
91	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
92	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
93	Montefiore Medical Center-Wakefield Campus	Bronx	New York	United States	10466
94	Glens Falls Hospital	Glens Falls	New York	United States	12801
95	Orange Regional Medical Center	Middletown	New York	United States	10940
96	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
97	Interlakes Foundation Inc-Rochester	Rochester	New York	United States	14623
98	University of Rochester	Rochester	New York	United States	14642
99	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
100	New York Medical College	Valhalla	New York	United States	10595
101	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
102	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
103	Duke University Medical Center	Durham	North Carolina	United States	27710
104	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
105	Southeast Clinical Oncology Research (SCOR) Consortium NCORP	Winston-Salem	North Carolina	United States	27104
106	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
107	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
108	Aultman Health Foundation	Canton	Ohio	United States	44710
109	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio	United States	45219
110	Case Western Reserve University	Cleveland	Ohio	United States	44106
111	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
112	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
113	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
114	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45420
115	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma	United States	73505
116	Saint John Medical Center	Tulsa	Oklahoma	United States	74104
117	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma	United States	74136
118	Providence Portland Medical Center	Portland	Oregon	United States	97213
119	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
120	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania	United States	18015
121	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
122	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
123	Saint Mary Medical and Regional Cancer Center	Langhorne	Pennsylvania	United States	19047
124	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
125	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
126	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
127	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
128	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
129	Pottstown Hospital	Pottstown	Pennsylvania	United States	19464
130	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania	United States	18840
131	Medical University of South Carolina	Charleston	South Carolina	United States	29425
132	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
133	East Tennessee State University	Johnson City	Tennessee	United States	37614-0054
134	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
135	Medical City Dallas Hospital	Dallas	Texas	United States	75230
136	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
137	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
138	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
139	Kaiser Permanente Washington	Seattle	Washington	United States	98112
140	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
141	West Virginia University Charleston Division	Charleston	West Virginia	United States	25304
142	Aurora Cancer Care-Glendale	Glendale	Wisconsin	United States	53212
143	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
144	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
145	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
146	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449
147	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066
148	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin	United States	53188

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: David H Lawson, Eastern Cooperative Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01989572
• Other Study ID Numbers: NCI-2013-02101; NCI-2013-02101; CALGB 500101; U10CA021115; ECOG-4697; CDR0000067568; SWOG-E4697; 9546; E4697; E4697; NCT00005034
• First Posted: Nov 21, 2013
• Last Update Posted: Jul 7, 2020
• Last Verified: Jun 1, 2020

• Additional relevant MeSH terms: Melanoma; Skin Neoplasms; Uveal Neoplasms; Recurrence; Sargramostim

Study Results

Participant Flow

Recruitment Details	The study was open between December 29, 1999 and October 31, 2006. A total of 815 patients were enrolled.

Arm/Group Title	Arm I (GM-CSF, Peptide Vaccine)	Arm II (GM-CSF Placebo, Peptide Vaccine)	Arm III (GM-CSF, Peptide Placebo)	Arm IV (GM-CSF Placebo, Peptide Placebo)	Arm V (GM-CSF)	Arm VI (GM-CSF Placebo)
Arm/Group Description	Patients receive GM-CSF (sargramostim) SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). sargramostim: Given SC peptide vaccine: Given SC	Patients receive GM-CSF (sargramostim) placebo SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). peptide vaccine: Given SC GM-CSF placebo: Given SC	Patients receive GM-CSF (sargramostim) SC on days 1-14 and peptide placebo mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). sargramostim: Given SC peptide placebo: Given SC	Patients receive GM-CSF placebo SC on days 1-14 and peptide placebo on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). GM-CSF placebo: Given SC peptide placebo: Given SC	Patients receive GM-CSF (sargramostim) SC on days 1-14. sargramostim: Given SC	Patients receive GM-CSF (sargramostim) placebo SC on days 1-14. GM-CSF placebo: Given SC
Period Title: Overall Study
STARTED	109	111	109	107	190	189
Treated	104	110	107	104	186	171
COMPLETED	54	53	47	56	92	79
NOT COMPLETED	55	58	62	51	98	110

Baseline Characteristics

Arm/Group Title	Arm I (GM-CSF, Peptide Vaccine)	Arm II (GM-CSF Placebo, Peptide Vaccine)	Arm III (GM-CSF, Peptide Placebo)	Arm IV (GM-CSF Placebo, Peptide Placebo)	Arm V (GM-CSF)	Arm VI (GM-CSF Placebo)	Total
Arm/Group Description	Patients receive GM-CSF (sargramostim) SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). sargramostim: Given SC peptide vaccine: Given SC	Patients receive GM-CSF (sargramostim) placebo SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). peptide vaccine: Given SC GM-CSF placebo: Given SC	Patients receive GM-CSF (sargramostim) SC on days 1-14 and peptide placebo mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). sargramostim: Given SC peptide placebo: Given SC	Patients receive GM-CSF placebo SC on days 1-14 and peptide placebo on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). GM-CSF placebo: Given SC peptide placebo: Given SC	Patients receive GM-CSF (sargramostim) SC on days 1-14. sargramostim: Given SC	Patients receive GM-CSF (sargramostim) placebo SC on days 1-14. GM-CSF placebo: Given SC	Total of all reporting groups
Overall Participants	109	111	109	107	190	189	815
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60	56	57	58	60	57	58
Sex/Gender, Customized (participants) [Number]
Female	48 44%	45 40.5%	45 41.3%	39 36.4%	77 40.5%	77 40.7%	331 40.6%
Male	61 56%	66 59.5%	64 58.7%	68 63.6%	112 58.9%	112 59.3%	483 59.3%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival is defined as time from randomization to death from any cause.
Time Frame	assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry, and annually if >5 years, up to year 15

Outcome Measure Data

Analysis Population Description

all randomized patients, regardless of eligibility

Arm/Group Title	GM-CSF	GM-CSF Placebo
Arm/Group Description	Patients received GM-CSF in the trial, including patients on arms I, III, V.	Patients who did not receive GM-CSF (ie, received GM-CSF placebo) in the trial, including patients on arms II, IV and VI
Measure Participants	408	407
Median (95% Confidence Interval) [months]	69.6	59.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GM-CSF, GM-CSF Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.528
	Comments
	Method	Log Rank
	Comments	stratifying on HLA-A2 status, site of metastases and number of metastatic lesions.

2. Primary Outcome

Title	Recurrence Free Survival
Description	Recurrence free survival is defined as time from randomization to first disease recurrence or death from any cause (whichever occur first), censoring cases without recurrence or death at the last date of known free of recurrence free survival events. Disease recurrence was determined based on positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease, or a positive brain CT or MRI scan or CSF cytology.
Time Frame	assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry, and annually if >5 years, up to year 15

Outcome Measure Data

Analysis Population Description

all randomized patients, regardless of eligibility

Arm/Group Title	GM-CSF	GM-CSF Placebo
Arm/Group Description	Patients received GM-CSF in the trial, including patients on arms I, III, V.	Patients who did not receive GM-CSF (ie, received GM-CSF placebo) in the trial, including patients on arms II, IV and VI
Measure Participants	408	407
Median (95% Confidence Interval) [months]	11.4	8.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GM-CSF, GM-CSF Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.131
	Comments
	Method	Log Rank
	Comments	stratifying on HLA-A2 status, site of metastases, and number of metastatic lesions

3. Secondary Outcome

Title	Overall Survival in Human Leukocyte Antigens-A2 (HLA-A2) Positive Patients
Description	Overall survival is defined as time from randomization to death from any cause.
Time Frame	assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry, and annually if >5 years,up to year 15

Outcome Measure Data

Analysis Population Description

all HLA-A2 positive patients

Arm/Group Title	Peptide Vaccination	Peptide Placebo
Arm/Group Description	Patients who were HLA-A2 positive and received peptide vaccine in the trial, including 109 patients on arm I and 111 patients on arm II.	Patients who were HLA-A2 positive and received peptide placebo in the trial, including 109 patients on arms III and 107 patients on arm IV
Measure Participants	220	216
Median (95% Confidence Interval) [months]	68.6	63.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GM-CSF, GM-CSF Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.60
	Comments
	Method	Log Rank
	Comments	stratifying on GM-CSF, site of metastases and number of metastatic lesions

4. Secondary Outcome

Title	Recurrence Free Survival in HLA-A2 Positive Patients
Description	Recurrence free survival is defined as time from randomization to first disease recurrence or death from any cause (whichever occur first), censoring cases without recurrence or death at the last date of known free of recurrence free survival events. Disease recurrence was determined based on positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease, or a positive brain CT or MRI scan or CSF cytology.
Time Frame	assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry, and annually if >5 years, up to year 15

Outcome Measure Data

Analysis Population Description

all HLA-A2 positive patients

Arm/Group Title	Peptide Vaccination	Peptide Placebo
Arm/Group Description	Patients who were HLA-A2 positive and received peptide vaccine in the trial, including 109 patients on arm I and 111 patients on arm II.	Patients who were HLA-A2 positive and received peptide placebo in the trial, including 109 patients on arms III and 107 patients on arm IV
Measure Participants	220	216
Median (95% Confidence Interval) [months]	11.5	9.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GM-CSF, GM-CSF Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments	stratifying on GM-CSF, site of metastases and number of metastatic lesions
	Method	Log Rank
	Comments

5. Secondary Outcome

Title	5-year Overall Survival Rate
Description	Overall survival is defined as time from randomization to death from any cause, and 5-year overall survival rate is estimated via Kaplan-Meier method.
Time Frame	assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry, and annually if >5 years, up to year 15

Outcome Measure Data

Analysis Population Description

all randomized patients, regardless of eligibility

Arm/Group Title	Arm I (GM-CSF, Peptide Vaccine)	Arm II (GM-CSF Placebo, Peptide Vaccine)	Arm III (GM-CSF, Peptide Placebo)	Arm IV (GM-CSF Placebo, Peptide Placebo)	Arm V (GM-CSF)	Arm VI (GM-CSF Placebo)
Arm/Group Description	Patients receive GM-CSF (sargramostim) SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). sargramostim: Given SC peptide vaccine: Given SC	Patients receive GM-CSF (sargramostim) placebo SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). peptide vaccine: Given SC GM-CSF placebo: Given SC	Patients receive GM-CSF (sargramostim) SC on days 1-14 and peptide placebo mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). sargramostim: Given SC peptide placebo: Given SC	Patients receive GM-CSF placebo SC on days 1-14 and peptide placebo on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). GM-CSF placebo: Given SC peptide placebo: Given SC	Patients receive GM-CSF (sargramostim) SC on days 1-14. sargramostim: Given SC	Patients receive GM-CSF (sargramostim) placebo SC on days 1-14. GM-CSF placebo: Given SC
Measure Participants	109	111	109	107	190	189
Number (95% Confidence Interval) [percentage of participants]	55.5 50.9%	51.9 46.8%	51.1 46.9%	51.6 48.2%	51.2 26.9%	46.7 24.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GM-CSF, GM-CSF Placebo, Arm III (GM-CSF, Peptide Placebo), Arm IV (GM-CSF Placebo, Peptide Placebo)
	Comments	Treatment arm comparison in patients with positive HLA-A2 status
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.88
	Comments
	Method	Log Rank
	Comments	stratifying on site of metastases and number of metastatic lesions

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm V (GM-CSF), Arm VI (GM-CSF Placebo)
	Comments	Treatment arm comparison in patients with negative HLA-A2 status
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	Log Rank
	Comments	stratifying on site of metastases and number of metastatic lesions

6. Secondary Outcome

Title	5-year Recurrence Free Survival Rate
Description	Recurrence free survival is defined as time from randomization to first disease recurrence or death from any cause (whichever occur first), censoring cases without recurrence or death at the last date of known free of recurrence free survival events, and 5-year overall survival rate is estimated via Kaplan-Meier method. Disease recurrence was determined based on positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease, or a positive brain CT or MRI scan or CSF cytology.
Time Frame	assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry, and annually if >5 years, up to year 15

Outcome Measure Data

Analysis Population Description

all randomized patients, regardless of eligibility

Arm/Group Title	Arm I (GM-CSF, Peptide Vaccine)	Arm II (GM-CSF Placebo, Peptide Vaccine)	Arm III (GM-CSF, Peptide Placebo)	Arm IV (GM-CSF Placebo, Peptide Placebo)	Arm V (GM-CSF)	Arm VI (GM-CSF Placebo)
Arm/Group Description	Patients receive GM-CSF (sargramostim) SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). sargramostim: Given SC peptide vaccine: Given SC	Patients receive GM-CSF (sargramostim) placebo SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). peptide vaccine: Given SC GM-CSF placebo: Given SC	Patients receive GM-CSF (sargramostim) SC on days 1-14 and peptide placebo mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). sargramostim: Given SC peptide placebo: Given SC	Patients receive GM-CSF placebo SC on days 1-14 and peptide placebo on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). GM-CSF placebo: Given SC peptide placebo: Given SC	Patients receive GM-CSF (sargramostim) SC on days 1-14. sargramostim: Given SC	Patients receive GM-CSF (sargramostim) placebo SC on days 1-14. GM-CSF placebo: Given SC
Measure Participants	109	111	109	107	190	189
Number (95% Confidence Interval) [percentage of participants]	32.4 29.7%	33.2 29.9%	31.3 28.7%	28.0 26.2%	30.6 16.1%	22.9 12.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GM-CSF, GM-CSF Placebo, Arm III (GM-CSF, Peptide Placebo), Arm IV (GM-CSF Placebo, Peptide Placebo)
	Comments	Treatment arm comparison in patients with positive HLA-A2 status
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.91
	Comments
	Method	Log Rank
	Comments	stratifying on site of metastases and number of metastatic lesions

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm V (GM-CSF), Arm VI (GM-CSF Placebo)
	Comments	Treatment arm comparisons in patients with negative HLA-A2 status
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Log Rank
	Comments	stratifying on site of metastases and number of metastatic lesions

Adverse Events

Time Frame	Assessed every cycle (1 cycle=28 days) for cycles 1, 2, 3, and 4; after cycle 4, assessed every 3 months (at the completion of cycles 7, 10, 13) while on treatment and for 30 days after the end of treatment
Adverse Event Reporting Description	After off treatment, if the patient experienced any clinical problems possibly related to the protocol treatment, the clinical problems were also reported per the standard ECOG follow-up schedule: every 3 months if patient is <2 years from study entry, every 6 months if patient is 2-5 years from study entry, and every 12 months if >5 years.
Arm/Group Title	Arm I (GM-CSF, Peptide Vaccine)		Arm II (GM-CSF Placebo, Peptide Vaccine)		Arm III (GM-CSF, Peptide Placebo)		Arm IV (GM-CSF Placebo, Peptide Placebo)		Arm V (GM-CSF)		Arm VI (GM-CSF Placebo)
Arm/Group Description	Arm I (GM-CSF, peptide vaccine) Patients receive GM-CSF (sargramostim) SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). sargramostim: Given SC peptide vaccine: Given SC		Arm II (GM-CSF placebo, peptide vaccine) Patients receive GM-CSF (sargramostim) placebo SC on days 1-14 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). peptide vaccine: Given SC GM-CSF placebo: Given SC		Arm III (GM-CSF, peptide placebo) Patients receive GM-CSF (sargramostim) SC on days 1-14 and peptide placebo mixed with either incomplete Freund's adjuvant or Montanide ISA-51 VG SC on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). sargramostim: Given SC peptide placebo: Given SC		Arm IV (GM-CSF placebo, peptide placebo) Patients receive GM-CSF placebo SC on days 1-14 and peptide placebo on days 1 and 15 (course 1) and day 1 (course 2 and subsequent courses). GM-CSF placebo: Given SC peptide placebo: Given SC		Patients receive GM-CSF (sargramostim) SC on days 1-14. sargramostim: Given SC		Patients receive GM-CSF (sargramostim) placebo SC on days 1-14. GM-CSF placebo: Given SC
All Cause Mortality
	Arm I (GM-CSF, Peptide Vaccine)		Arm II (GM-CSF Placebo, Peptide Vaccine)		Arm III (GM-CSF, Peptide Placebo)		Arm IV (GM-CSF Placebo, Peptide Placebo)		Arm V (GM-CSF)		Arm VI (GM-CSF Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (GM-CSF, Peptide Vaccine)		Arm II (GM-CSF Placebo, Peptide Vaccine)		Arm III (GM-CSF, Peptide Placebo)		Arm IV (GM-CSF Placebo, Peptide Placebo)		Arm V (GM-CSF)		Arm VI (GM-CSF Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/104 (11.5%)		17/110 (15.5%)		15/107 (14%)		9/104 (8.7%)		22/186 (11.8%)		12/171 (7%)
Blood and lymphatic system disorders
Anemia	0/104 (0%)		0/110 (0%)		0/107 (0%)		1/104 (1%)		0/186 (0%)		1/171 (0.6%)
Cardiac disorders
Cardiac disorders - Other, specify	0/104 (0%)		0/110 (0%)		0/107 (0%)		1/104 (1%)		0/186 (0%)		0/171 (0%)
Myocardial infarction	1/104 (1%)		0/110 (0%)		1/107 (0.9%)		0/104 (0%)		0/186 (0%)		0/171 (0%)
Gastrointestinal disorders
Nausea	0/104 (0%)		0/110 (0%)		0/107 (0%)		0/104 (0%)		1/186 (0.5%)		0/171 (0%)
Diarrhea	0/104 (0%)		0/110 (0%)		0/107 (0%)		0/104 (0%)		0/186 (0%)		1/171 (0.6%)
Abdominal pain	0/104 (0%)		0/110 (0%)		0/107 (0%)		0/104 (0%)		1/186 (0.5%)		0/171 (0%)
General disorders
Fatigue	0/104 (0%)		0/110 (0%)		3/107 (2.8%)		0/104 (0%)		1/186 (0.5%)		1/171 (0.6%)
Injection site reaction	2/104 (1.9%)		9/110 (8.2%)		2/107 (1.9%)		2/104 (1.9%)		1/186 (0.5%)		1/171 (0.6%)
Non-cardiac chest pain	0/104 (0%)		0/110 (0%)		1/107 (0.9%)		0/104 (0%)		2/186 (1.1%)		0/171 (0%)
Pain	0/104 (0%)		0/110 (0%)		1/107 (0.9%)		0/104 (0%)		1/186 (0.5%)		0/171 (0%)
Immune system disorders
Anaphylaxis	1/104 (1%)		1/110 (0.9%)		1/107 (0.9%)		0/104 (0%)		1/186 (0.5%)		0/171 (0%)
Flushing	0/104 (0%)		1/110 (0.9%)		0/107 (0%)		0/104 (0%)		0/186 (0%)		0/171 (0%)
Infections and infestations
Infections and infestations - Other, spe	0/104 (0%)		0/110 (0%)		0/107 (0%)		0/104 (0%)		0/186 (0%)		1/171 (0.6%)
Infections and infestations - Other, spe	0/104 (0%)		1/110 (0.9%)		0/107 (0%)		0/104 (0%)		0/186 (0%)		1/171 (0.6%)
Infections and infestations - Other, spe	1/104 (1%)		0/110 (0%)		0/107 (0%)		0/104 (0%)		0/186 (0%)		0/171 (0%)
Investigations
White blood cell decreased	0/104 (0%)		0/110 (0%)		2/107 (1.9%)		0/104 (0%)		0/186 (0%)		0/171 (0%)
Neutrophil count decreased	0/104 (0%)		2/110 (1.8%)		2/107 (1.9%)		2/104 (1.9%)		2/186 (1.1%)		2/171 (1.2%)
Weight gain	0/104 (0%)		0/110 (0%)		0/107 (0%)		0/104 (0%)		0/186 (0%)		1/171 (0.6%)
Weight loss	0/104 (0%)		0/110 (0%)		0/107 (0%)		1/104 (1%)		0/186 (0%)		0/171 (0%)
Blood bilirubin increased	0/104 (0%)		1/110 (0.9%)		2/107 (1.9%)		3/104 (2.9%)		2/186 (1.1%)		2/171 (1.2%)
Aspartate aminotransferase increased	0/104 (0%)		0/110 (0%)		0/107 (0%)		0/104 (0%)		0/186 (0%)		1/171 (0.6%)
Creatinine increased	0/104 (0%)		0/110 (0%)		0/107 (0%)		1/104 (1%)		1/186 (0.5%)		1/171 (0.6%)
Musculoskeletal and connective tissue disorders
Arthritis	0/104 (0%)		1/110 (0.9%)		0/107 (0%)		0/104 (0%)		0/186 (0%)		0/171 (0%)
Musculoskeletal and connective tissue di	1/104 (1%)		0/110 (0%)		0/107 (0%)		0/104 (0%)		0/186 (0%)		0/171 (0%)
Arthralgia	0/104 (0%)		1/110 (0.9%)		4/107 (3.7%)		0/104 (0%)		1/186 (0.5%)		0/171 (0%)
Myalgia	0/104 (0%)		2/110 (1.8%)		1/107 (0.9%)		0/104 (0%)		0/186 (0%)		1/171 (0.6%)
Nervous system disorders
Dizziness	0/104 (0%)		1/110 (0.9%)		0/107 (0%)		0/104 (0%)		0/186 (0%)		0/171 (0%)
Nervous system disorders - Other, specif	0/104 (0%)		0/110 (0%)		0/107 (0%)		0/104 (0%)		0/186 (0%)		1/171 (0.6%)
Peripheral motor neuropathy	0/104 (0%)		1/110 (0.9%)		0/107 (0%)		0/104 (0%)		0/186 (0%)		1/171 (0.6%)
Peripheral sensory neuropathy	0/104 (0%)		1/110 (0.9%)		0/107 (0%)		0/104 (0%)		1/186 (0.5%)		0/171 (0%)
Syncope	1/104 (1%)		0/110 (0%)		1/107 (0.9%)		0/104 (0%)		0/186 (0%)		0/171 (0%)
Headache	3/104 (2.9%)		0/110 (0%)		0/107 (0%)		1/104 (1%)		6/186 (3.2%)		0/171 (0%)
Psychiatric disorders
Insomnia	0/104 (0%)		0/110 (0%)		0/107 (0%)		0/104 (0%)		1/186 (0.5%)		0/171 (0%)
Depression	0/104 (0%)		0/110 (0%)		0/107 (0%)		0/104 (0%)		1/186 (0.5%)		0/171 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/104 (0%)		1/110 (0.9%)		0/107 (0%)		0/104 (0%)		3/186 (1.6%)		0/171 (0%)
Skin and subcutaneous tissue disorders
Pruritus	0/104 (0%)		0/110 (0%)		1/107 (0.9%)		0/104 (0%)		0/186 (0%)		0/171 (0%)
Rash maculo-papular	2/104 (1.9%)		1/110 (0.9%)		1/107 (0.9%)		0/104 (0%)		2/186 (1.1%)		0/171 (0%)
Urticaria	1/104 (1%)		1/110 (0.9%)		0/107 (0%)		0/104 (0%)		1/186 (0.5%)		0/171 (0%)
Vascular disorders
Thromboembolic event	1/104 (1%)		0/110 (0%)		1/107 (0.9%)		0/104 (0%)		0/186 (0%)		0/171 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (GM-CSF, Peptide Vaccine)		Arm II (GM-CSF Placebo, Peptide Vaccine)		Arm III (GM-CSF, Peptide Placebo)		Arm IV (GM-CSF Placebo, Peptide Placebo)		Arm V (GM-CSF)		Arm VI (GM-CSF Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	104/104 (100%)		109/110 (99.1%)		105/107 (98.1%)		102/104 (98.1%)		180/186 (96.8%)		143/171 (83.6%)
Blood and lymphatic system disorders
Anemia	21/104 (20.2%)		15/110 (13.6%)		26/107 (24.3%)		18/104 (17.3%)		25/186 (13.4%)		16/171 (9.4%)
Cardiac disorders
Cardiac disorders - Other, specify	6/104 (5.8%)		4/110 (3.6%)		9/107 (8.4%)		7/104 (6.7%)		6/186 (3.2%)		5/171 (2.9%)
Gastrointestinal disorders
Nausea	24/104 (23.1%)		24/110 (21.8%)		21/107 (19.6%)		15/104 (14.4%)		36/186 (19.4%)		19/171 (11.1%)
Vomiting	6/104 (5.8%)		5/110 (4.5%)		5/107 (4.7%)		4/104 (3.8%)		8/186 (4.3%)		3/171 (1.8%)
Diarrhea	16/104 (15.4%)		8/110 (7.3%)		11/107 (10.3%)		11/104 (10.6%)		27/186 (14.5%)		19/171 (11.1%)
Abdominal pain	3/104 (2.9%)		2/110 (1.8%)		3/107 (2.8%)		3/104 (2.9%)		11/186 (5.9%)		6/171 (3.5%)
General disorders
Fatigue	67/104 (64.4%)		53/110 (48.2%)		58/107 (54.2%)		57/104 (54.8%)		81/186 (43.5%)		66/171 (38.6%)
Fever	17/104 (16.3%)		19/110 (17.3%)		15/107 (14%)		6/104 (5.8%)		21/186 (11.3%)		13/171 (7.6%)
Chills	24/104 (23.1%)		13/110 (11.8%)		14/107 (13.1%)		7/104 (6.7%)		24/186 (12.9%)		12/171 (7%)
General disorders and administration sit	5/104 (4.8%)		6/110 (5.5%)		6/107 (5.6%)		5/104 (4.8%)		8/186 (4.3%)		5/171 (2.9%)
Injection site reaction	99/104 (95.2%)		100/110 (90.9%)		98/107 (91.6%)		89/104 (85.6%)		147/186 (79%)		43/171 (25.1%)
Non-cardiac chest pain	0/104 (0%)		1/110 (0.9%)		3/107 (2.8%)		0/104 (0%)		10/186 (5.4%)		1/171 (0.6%)
Pain	8/104 (7.7%)		9/110 (8.2%)		5/107 (4.7%)		10/104 (9.6%)		10/186 (5.4%)		11/171 (6.4%)
Injury, poisoning and procedural complications
Bruising	1/104 (1%)		4/110 (3.6%)		0/107 (0%)		6/104 (5.8%)		3/186 (1.6%)		4/171 (2.3%)
Investigations
White blood cell decreased	7/104 (6.7%)		9/110 (8.2%)		8/107 (7.5%)		12/104 (11.5%)		7/186 (3.8%)		13/171 (7.6%)
Neutrophil count decreased	3/104 (2.9%)		10/110 (9.1%)		5/107 (4.7%)		10/104 (9.6%)		8/186 (4.3%)		11/171 (6.4%)
Platelet count decreased	6/104 (5.8%)		4/110 (3.6%)		8/107 (7.5%)		2/104 (1.9%)		5/186 (2.7%)		6/171 (3.5%)
Weight gain	7/104 (6.7%)		6/110 (5.5%)		6/107 (5.6%)		10/104 (9.6%)		7/186 (3.8%)		8/171 (4.7%)
Weight loss	2/104 (1.9%)		7/110 (6.4%)		5/107 (4.7%)		6/104 (5.8%)		8/186 (4.3%)		8/171 (4.7%)
Alkaline phosphatase increased	7/104 (6.7%)		5/110 (4.5%)		3/107 (2.8%)		10/104 (9.6%)		9/186 (4.8%)		15/171 (8.8%)
Blood bilirubin increased	5/104 (4.8%)		4/110 (3.6%)		9/107 (8.4%)		3/104 (2.9%)		9/186 (4.8%)		8/171 (4.7%)
Aspartate aminotransferase increased	5/104 (4.8%)		7/110 (6.4%)		2/107 (1.9%)		7/104 (6.7%)		14/186 (7.5%)		12/171 (7%)
Creatinine increased	5/104 (4.8%)		6/110 (5.5%)		5/107 (4.7%)		8/104 (7.7%)		10/186 (5.4%)		8/171 (4.7%)
Metabolism and nutrition disorders
Anorexia	7/104 (6.7%)		7/110 (6.4%)		6/107 (5.6%)		7/104 (6.7%)		17/186 (9.1%)		9/171 (5.3%)
Hypoalbuminemia	12/104 (11.5%)		14/110 (12.7%)		20/107 (18.7%)		15/104 (14.4%)		24/186 (12.9%)		18/171 (10.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	20/104 (19.2%)		23/110 (20.9%)		32/107 (29.9%)		18/104 (17.3%)		37/186 (19.9%)		27/171 (15.8%)
Bone pain	10/104 (9.6%)		11/110 (10%)		14/107 (13.1%)		7/104 (6.7%)		15/186 (8.1%)		10/171 (5.8%)
Myalgia	25/104 (24%)		32/110 (29.1%)		38/107 (35.5%)		25/104 (24%)		57/186 (30.6%)		26/171 (15.2%)
Nervous system disorders
Dysgeusia	3/104 (2.9%)		2/110 (1.8%)		5/107 (4.7%)		4/104 (3.8%)		10/186 (5.4%)		4/171 (2.3%)
Dizziness	5/104 (4.8%)		1/110 (0.9%)		4/107 (3.7%)		6/104 (5.8%)		7/186 (3.8%)		8/171 (4.7%)
Peripheral sensory neuropathy	4/104 (3.8%)		4/110 (3.6%)		6/107 (5.6%)		13/104 (12.5%)		10/186 (5.4%)		7/171 (4.1%)
Headache	28/104 (26.9%)		24/110 (21.8%)		22/107 (20.6%)		21/104 (20.2%)		42/186 (22.6%)		36/171 (21.1%)
Psychiatric disorders
Insomnia	3/104 (2.9%)		2/110 (1.8%)		5/107 (4.7%)		6/104 (5.8%)		9/186 (4.8%)		9/171 (5.3%)
Anxiety	2/104 (1.9%)		4/110 (3.6%)		6/107 (5.6%)		5/104 (4.8%)		8/186 (4.3%)		2/171 (1.2%)
Depression	3/104 (2.9%)		3/110 (2.7%)		2/107 (1.9%)		6/104 (5.8%)		10/186 (5.4%)		4/171 (2.3%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	4/104 (3.8%)		4/110 (3.6%)		4/107 (3.7%)		6/104 (5.8%)		11/186 (5.9%)		7/171 (4.1%)
Pruritus	8/104 (7.7%)		10/110 (9.1%)		15/107 (14%)		5/104 (4.8%)		17/186 (9.1%)		5/171 (2.9%)
Rash maculo-papular	27/104 (26%)		22/110 (20%)		33/107 (30.8%)		13/104 (12.5%)		31/186 (16.7%)		17/171 (9.9%)
Skin and subcutaneous tissue disorders -	15/104 (14.4%)		16/110 (14.5%)		11/107 (10.3%)		14/104 (13.5%)		22/186 (11.8%)		6/171 (3.5%)
Vascular disorders
Hot flashes	3/104 (2.9%)		1/110 (0.9%)		6/107 (5.6%)		3/104 (2.9%)		10/186 (5.4%)		3/171 (1.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.