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CompletedNCT01989572Updated Jun 24, 2026Results posted

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

A Phase 3 interventional study of Laboratory Biomarker Analysis and Placebo in Iris Melanoma, Medium/Large Size Posterior Uveal Melanoma and Mucosal Melanoma, sponsored by National Cancer Institute (NCI). Completed at 148 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-24.

Sponsored by National Cancer Institute (NCI) · Phase 3, Interventional, and Prevention

From the registry’s dates

  • Registered 13 years 8 months after the study started (first participant enrolled Feb 2000, registered Nov 2013).
Phase
Phase 3
Study type
Interventional
Enrollment
815
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

PRIMARY OBJECTIVES:

I. 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:

I. 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.

II. 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.

III. 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.

IV. 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.

V. 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.

02

Conditions studied

  • 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
03

In context

Uveal Melanoma

103 studies on the registry are indexed under Uveal Melanoma; 38 are open to participants now.

This study's enrollment of 815 is above the median of 42 across 93 interventional studies indexed under Uveal Melanoma.

Browse Uveal Melanoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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
05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Factorial assignment
Masking
Double (Participant, Investigator)
Enrollment
815 participants (actual)

Study arms

  • 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 · Biological: Sargramostim · Biological: Tyrosinase Peptide

  • 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 · Other: Placebo · Biological: Tyrosinase Peptide

  • 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 · Other: Placebo · Biological: Sargramostim

  • 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 · Other: Placebo

  • Experimental
    Arm V (sargramostim)

    Patients receive sargramostim SC on days 1-14.

    Other: Laboratory Biomarker Analysis · Biological: Sargramostim

  • Placebo comparator
    Arm VI (sargramostim placebo)

    Patients receive sargramostim placebo SC on days 1-14.

    Other: Laboratory Biomarker Analysis · Other: Placebo

Interventions

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • OtherPlacebo

    Given GM-CSF placebo SC

    Also known as: placebo therapy, PLCB, sham therapy

  • OtherPlacebo

    Given peptide placebo SC

    Also known as: placebo therapy, PLCB, sham therapy

  • BiologicalSargramostim

    Given SC

    Also known as: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin

  • BiologicalTyrosinase Peptide

    Given SC

    Also known as: Tyrosinase Peptides

06

What researchers measure

Primary outcomes

  1. Overall Survival

    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

  2. Recurrence Free Survival

    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

Secondary outcomes

  1. Overall Survival in Human Leukocyte Antigens-A2 (HLA-A2) Positive Patients

    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

  2. Recurrence Free Survival in HLA-A2 Positive Patients

    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

  3. 5-year Overall Survival Rate

    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

  4. 5-year Recurrence Free Survival Rate

    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

07

Results

Posted Aug 12, 2014

Participant flow

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

Participant flow — Overall Study
MilestoneArm 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)
Started109111109107190189
Treated104110107104186171
Completed545347569279
Not completed5558625198110
Withdrew: Lack of efficacy354848437179
Withdrew: Adverse event213030
Withdrew: Death000010
Withdrew: Withdrawal by subject4151124
Withdrew: Complicating disease112010
Withdrew: Error211111
Withdrew: Maximum dose reached010010
Withdrew: Unknown/not specify341335
Withdrew: Not start protocol therapy5123418
Withdrew: Alternative therapy300013

Outcome measures

PrimaryOverall Survival

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
Reported as:
Median · months
Overall Survival
monthsGM-CSFGM-CSF Placebo
Overall Survival69.6 (53.4 to 83.5)59.3 (44.4 to 77.3)
Statistical analysis
  • GM-CSF vs GM-CSF Placebo · Log Rank · p = 0.528stratifying on HLA-A2 status, site of metastases and number of metastatic lesions.
PrimaryRecurrence Free Survival

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
Reported as:
Median · months
Recurrence Free Survival
monthsGM-CSFGM-CSF Placebo
Recurrence Free Survival11.4 (9.4 to 14.8)8.8 (7.5 to 11.2)
Statistical analysis
  • GM-CSF vs GM-CSF Placebo · Log Rank · p = 0.131stratifying on HLA-A2 status, site of metastases, and number of metastatic lesions
SecondaryOverall Survival in Human Leukocyte Antigens-A2 (HLA-A2) Positive Patients

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
Reported as:
Median · months
Overall Survival in Human Leukocyte Antigens-A2 (HLA-A2) Positive Patients
monthsPeptide VaccinationPeptide Placebo
Overall Survival in Human Leukocyte Antigens-A2 (HLA-A2) Positive Patients68.6 (47.0 to 92.3)63.3 (49.2 to 105.0)
Statistical analysis
  • Peptide Vaccination vs Peptide Placebo · Log Rank · p = 0.60stratifying on GM-CSF, site of metastases and number of metastatic lesions
SecondaryRecurrence Free Survival in HLA-A2 Positive Patients

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
Reported as:
Median · months
Recurrence Free Survival in HLA-A2 Positive Patients
monthsPeptide VaccinationPeptide Placebo
Recurrence Free Survival in HLA-A2 Positive Patients11.5 (8.7 to 20.4)9.8 (7.7 to 15.5)
Statistical analysis
  • Peptide Vaccination vs Peptide Placebo · Log Rank · p = 0.71 (stratifying on GM-CSF, site of metastases and number of metastatic lesions)
Secondary5-year Overall Survival Rate

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
Reported as:
Number · percentage of participants
5-year Overall Survival Rate
percentage of participantsArm 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)
5-year Overall Survival Rate55.5 (45.4 to 64.5)51.9 (42.0 to 61.0)51.1 (41.2 to 60.1)51.6 (41.4 to 60.9)51.2 (43.8 to 58.2)46.7 (39.3 to 53.8)
Statistical analysis
  • Arm I (GM-CSF, Peptide Vaccine) vs Arm II (GM-CSF Placebo, Peptide Vaccine) vs Arm III (GM-CSF, Peptide Placebo) vs Arm IV (GM-CSF Placebo, Peptide Placebo) · Log Rank · p = 0.88stratifying on site of metastases and number of metastatic lesions
  • Arm V (GM-CSF) vs Arm VI (GM-CSF Placebo) · Log Rank · p = 0.69stratifying on site of metastases and number of metastatic lesions
Secondary5-year Recurrence Free Survival Rate

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
Reported as:
Number · percentage of participants
5-year Recurrence Free Survival Rate
percentage of participantsArm 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)
5-year Recurrence Free Survival Rate32.4 (23.6 to 41.5)33.2 (24.4 to 42.2)31.3 (22.8 to 40.2)28.0 (19.7 to 36.9)30.6 (24.1 to 37.3)22.9 (17.1 to 29.2)
Statistical analysis
  • Arm I (GM-CSF, Peptide Vaccine) vs Arm II (GM-CSF Placebo, Peptide Vaccine) vs Arm III (GM-CSF, Peptide Placebo) vs Arm IV (GM-CSF Placebo, Peptide Placebo) · Log Rank · p = 0.91stratifying on site of metastases and number of metastatic lesions
  • Arm V (GM-CSF) vs Arm VI (GM-CSF Placebo) · Log Rank · p = 0.13stratifying on site of metastases and number of metastatic lesions

Adverse events

Collected over 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. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm I (GM-CSF, Peptide Vaccine)—12/104 (11.5%)104/104 (100%)
Arm II (GM-CSF Placebo, Peptide Vaccine)—17/110 (15.5%)109/110 (99.1%)
Arm III (GM-CSF, Peptide Placebo)—15/107 (14%)105/107 (98.1%)
Arm IV (GM-CSF Placebo, Peptide Placebo)—9/104 (8.7%)102/104 (98.1%)
Arm V (GM-CSF)—22/186 (11.8%)180/186 (96.8%)
Arm VI (GM-CSF Placebo)—12/171 (7%)143/171 (83.6%)
Most frequent serious events
Showing 10 of 39
Most frequent serious events
EventArm 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)
Injection site reactionGeneral disorders2/1049/1102/1072/1041/1861/171
ArthralgiaMusculoskeletal and connective tissue disorders0/1041/1104/1070/1041/1860/171
HeadacheNervous system disorders3/1040/1100/1071/1046/1860/171
Blood bilirubin increasedInvestigations0/1041/1102/1073/1042/1862/171
FatigueGeneral disorders0/1040/1103/1070/1041/1861/171
Neutrophil count decreasedInvestigations0/1042/1102/1072/1042/1862/171
Rash maculo-papularSkin and subcutaneous tissue disorders2/1041/1101/1070/1042/1860/171
White blood cell decreasedInvestigations0/1040/1102/1070/1040/1860/171
MyalgiaMusculoskeletal and connective tissue disorders0/1042/1101/1070/1040/1861/171
DyspneaRespiratory, thoracic and mediastinal disorders0/1041/1100/1070/1043/1860/171
Most frequent other events
Showing 10 of 40
Most frequent other events
EventArm 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)
Injection site reactionGeneral disorders99/104100/11098/10789/104147/18643/171
FatigueGeneral disorders67/10453/11058/10757/10481/18666/171
MyalgiaMusculoskeletal and connective tissue disorders25/10432/11038/10725/10457/18626/171
Rash maculo-papularSkin and subcutaneous tissue disorders27/10422/11033/10713/10431/18617/171
ArthralgiaMusculoskeletal and connective tissue disorders20/10423/11032/10718/10437/18627/171
HeadacheNervous system disorders28/10424/11022/10721/10442/18636/171
AnemiaBlood and lymphatic system disorders21/10415/11026/10718/10425/18616/171
ChillsGeneral disorders24/10413/11014/1077/10424/18612/171
NauseaGastrointestinal disorders24/10424/11021/10715/10436/18619/171
HypoalbuminemiaMetabolism and nutrition disorders12/10414/11020/10715/10424/18618/171

Baseline characteristics

All patients regardless of eligibility and treatment status

Age, Continuous
Age, Continuous(years)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
Median60 (27 to 83)56 (22 to 82)57 (23 to 87)58 (23 to 82)60 (19 to 88)57 (19 to 87)58 (19 to 88)
Sex/Gender, Customized
Sex/Gender, Customized(participants)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
Female484545397777331
Male61666468112112483
08

Study locations

148 sites
  • University of Alabama at Birmingham Cancer Center
    Birmingham, Alabama 35233, United States
  • Mobile Infirmary Medical Center
    Mobile, Alabama 36607, United States
  • Mayo Clinic in Arizona
    Scottsdale, Arizona 85259, United States
  • Banner University Medical Center - Tucson
    Tucson, Arizona 85719, United States
  • University of Arkansas for Medical Sciences
    Little Rock, Arkansas 72205, United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California 94704, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California 91010, United States
  • UC San Diego Moores Cancer Center
    La Jolla, California 92093, United States
  • Saint Joseph Hospital - Orange
    Orange, California 92868, United States
  • Stanford Cancer Institute Palo Alto
    Palo Alto, California 94304, United States
  • VA Palo Alto Health Care System
    Palo Alto, California 94304, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California 95817, United States
  • Kaiser Permanente-San Diego Mission
    San Diego, California 92108, United States
  • Naval Medical Center -San Diego
    San Diego, California 92134, United States
  • Veterans Administration-San Diego Medical Center
    San Diego, California 92161, United States
  • The Medical Center of Aurora
    Aurora, Colorado 80012, United States
  • Boulder Community Hospital
    Boulder, Colorado 80301, United States
  • SCL Health Saint Joseph Hospital
    Denver, Colorado 80218, United States
  • Swedish Medical Center
    Englewood, Colorado 80113, United States
  • Saint Mary's Hospital and Regional Medical Center
    Grand Junction, Colorado 81501, United States
  • Manchester Memorial Hospital
    Manchester, Connecticut 06040, United States
  • Southwest Florida Regional Medical Center
    Fort Myers, Florida 33901, United States
  • Baptist MD Anderson Cancer Center
    Jacksonville, Florida 32207, United States
  • Mayo Clinic in Florida
    Jacksonville, Florida 32224-9980, United States
  • Jupiter Medical Center
    Jupiter, Florida 33458, United States
  • Lakeland Regional Health Hollis Cancer Center
    Lakeland, Florida 33805, United States
  • Mount Sinai Medical Center
    Miami Beach, Florida 33140, United States
  • AdventHealth Orlando
    Orlando, Florida 32803, United States
  • Florida Cancer Specialists-West Palm Beach
    West Palm Beach, Florida 33401, United States
  • Cleveland Clinic-Weston
    Weston, Florida 33331, United States
  • Emory University Hospital/Winship Cancer Institute
    Atlanta, Georgia 30322, United States
  • Augusta University Medical Center
    Augusta, Georgia 30912, United States
  • Atlanta VA Medical Center
    Decatur, Georgia 30033, United States
  • Eisenhower Army Medical Center
    Fort Gordon, Georgia 30905-5650, United States
  • Medical Center of Central Georgia
    Macon, Georgia 31201, United States
  • South Georgia Medical Center/Pearlman Cancer Center
    Valdosta, Georgia 31602, United States
  • Saint Luke's Mountain States Tumor Institute
    Boise, Idaho 83712, United States
  • Rush - Copley Medical Center
    Aurora, Illinois 60504, United States
  • Northwestern University
    Chicago, Illinois 60611, United States
  • University of Chicago Comprehensive Cancer Center
    Chicago, Illinois 60637, United States
  • Loyola University Medical Center
    Maywood, Illinois 60153, United States
  • Memorial Medical Center
    Springfield, Illinois 62781, United States
  • Carle Cancer Center
    Urbana, Illinois 61801, United States
  • Indiana University/Melvin and Bren Simon Cancer Center
    Indianapolis, Indiana 46202, United States
  • IU Health Methodist Hospital
    Indianapolis, Indiana 46202, United States
  • IU Health Ball Memorial Hospital
    Muncie, Indiana 47303, United States
  • McFarland Clinic PC - Ames
    Ames, Iowa 50010, United States
  • Genesis Medical Center - East Campus
    Davenport, Iowa 52803, United States
  • Iowa Methodist Medical Center
    Des Moines, Iowa 50309, United States
  • Iowa-Wide Oncology Research Coalition NCORP
    Des Moines, Iowa 50309, United States
  • Medical Oncology and Hematology Associates-Des Moines
    Des Moines, Iowa 50309, United States
  • Siouxland Regional Cancer Center
    Sioux City, Iowa 51101, United States
  • University of Kansas Cancer Center
    Kansas City, Kansas 66160, United States
  • Wichita NCI Community Oncology Research Program
    Wichita, Kansas 67214, United States
  • The James Graham Brown Cancer Center at University of Louisville
    Louisville, Kentucky 40202, United States
  • Ochsner Health Center-Summa
    Baton Rouge, Louisiana 70809, United States
  • Ochsner Medical Center Jefferson
    New Orleans, Louisiana 70121, United States
  • Eastern Maine Medical Center
    Bangor, Maine 04401, United States
  • Anne Arundel Medical Center
    Annapolis, Maryland 21401, United States
  • Greater Baltimore Medical Center
    Baltimore, Maryland 21204, United States
  • Sinai Hospital of Baltimore
    Baltimore, Maryland 21215, United States
  • Johns Hopkins University/Sidney Kimmel Cancer Center
    Baltimore, Maryland 21287, United States
  • Tufts Medical Center
    Boston, Massachusetts 02111, United States
  • Massachusetts General Hospital Cancer Center
    Boston, Massachusetts 02114, United States
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02215, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02215, United States
  • Franklin Medical Center
    Greenfield, Massachusetts 01301, United States
  • Baystate Medical Center
    Springfield, Massachusetts 01199, United States
  • University of Michigan Comprehensive Cancer Center
    Ann Arbor, Michigan 48109, United States
  • Cancer Research Consortium of West Michigan NCORP
    Grand Rapids, Michigan 49503, United States
  • West Michigan Cancer Center
    Kalamazoo, Michigan 49007, United States
  • North Memorial Medical Health Center
    Robbinsdale, Minnesota 55422, United States
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
  • Hattiesburg Clinic - Hematology/Oncology Clinic
    Hattiesburg, Mississippi 39401, United States
  • University of Missouri - Ellis Fischel
    Columbia, Missouri 65212, United States
  • Cancer Research for the Ozarks NCORP
    Springfield, Missouri 65804, United States
  • Saint Louis-Cape Girardeau CCOP
    St Louis, Missouri 63141, United States
  • Saint Vincent Healthcare
    Billings, Montana 59101, United States
  • Montana Cancer Consortium NCORP
    Billings, Montana 59102, United States
  • CHI Health Saint Francis
    Grand Island, Nebraska 68803, United States
  • Nebraska Methodist Hospital
    Omaha, Nebraska 68114, United States
  • Alegent Health Immanuel Medical Center
    Omaha, Nebraska 68122, United States
  • Alegent Health Bergan Mercy Medical Center
    Omaha, Nebraska 68124, United States
  • Creighton University Medical Center
    Omaha, Nebraska 68131, United States
  • University of Nebraska Medical Center
    Omaha, Nebraska 68198, United States
  • University Medical Center of Southern Nevada
    Las Vegas, Nevada 89102, United States
  • Nevada Cancer Research Foundation CCOP
    Las Vegas, Nevada 89106, United States
  • Dartmouth Hitchcock Medical Center
    Lebanon, New Hampshire 03756, United States
  • Veterans Adminstration New Jersey Health Care System
    East Orange, New Jersey 07018-1095, United States
  • The Cancer Institute of New Jersey Hamilton
    Hamilton, New Jersey 08690, United States
  • Rutgers Cancer Institute of New Jersey
    New Brunswick, New Jersey 08903, United States
  • University of New Mexico Cancer Center
    Albuquerque, New Mexico 87102, United States
  • Glens Falls Hospital
    Glens Falls, New York 12801, United States
  • Orange Regional Medical Center
    Middletown, New York 10940, United States
  • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    New York, New York 10016, United States
  • Interlakes Foundation Inc-Rochester
    Rochester, New York 14623, United States
  • University of Rochester
    Rochester, New York 14642, United States
  • Stony Brook University Medical Center
    Stony Brook, New York 11794, United States
  • Montefiore Medical Center-Wakefield Campus
    The Bronx, New York 10466, United States
  • New York Medical College
    Valhalla, New York 10595, United States

Showing the first 100 of 148 sites.

09

References and documents

Publications

  • Lawson DH, Lee S, Zhao F, Tarhini AA, Margolin KA, Ernstoff MS, Atkins MB, Cohen GI, Whiteside TL, Butterfield LH, Kirkwood JM. Randomized, Placebo-Controlled, Phase III Trial of Yeast-Derived Granulocyte-Macrophage Colony-Stimulating Factor (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: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E4697). J Clin Oncol. 2015 Dec 1;33(34):4066-76. doi: 10.1200/JCO.2015.62.0500. Epub 2015 Sep 8. PubMed 26351350 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 24, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01989572
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Nov 21, 2013
Start date
Feb 23, 2000
Primary completion
Oct 8, 2012
Completion
Jan 31, 2013
Results posted
Aug 12, 2014
Last update
Jun 24, 2026

Study contacts

David H Lawson
principal investigator · Eastern Cooperative Oncology Group
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in May 2026. You cannot join it, but the record below documents what was studied.

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