Vaccine Therapy Using Melanoma Peptides for Cytotoxic T Cells and Helper T Cells in Treating Patients With Metastatic Melanoma

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ClinicalTrials.gov Identifier: NCT00071981

Recruitment Status : Completed

First Posted : November 6, 2003

Results First Posted : January 3, 2013

Last Update Posted : October 28, 2015

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Eastern Cooperative Oncology Group

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Melanoma (Skin)
Interventions	Biological: incomplete Freund's adjuvant Biological: melanoma helper peptide vaccine Biological: multi-epitope melanoma peptide vaccine Biological: sargramostim Biological: tetanus peptide melanoma vaccine
Enrollment	175

Participant Flow

Recruitment Details	This study was activated on March 21, 2005, and terminated on January 12, 2009 with the final accrual of 175 patients.22 ECOG institutions participated in the study.
Pre-assignment Details	This study involved a pre-registration before randomization. For patients with locally-typed HLA status, randomization immediately followed pre-registration. For central evaluation of HLA status, samples were submitted after pre-registration, and results of the evaluation must have been received from the central laboratory prior to randomization


Arm/Group Title	Arm I (12MP)	Arm II (12MP/Tet)	Arm III (12MP/6MHP)	Arm IV (6MHP)
Arm/Group Description	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...
Arm/Group Description	Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 (incomplete Freund's adjuvant) or Montanide ISA-51 VG (ISA-51) intradermally (ID) and subcutaneously (SC) on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection tetanus peptide melanoma vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising melanoma helper peptide vaccine (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection
Period Title: Overall Study
Started	47	43	37	48
Eligible	43	36	33	42
Treated	45	38	36	48
Eligible and Treated	41	33	32	42
Have CTL Response Data	40	30	29	41
Have Helper T Cell Response Data	37	27	25	39
Completed	1	2	0	3
Not Completed	46	41	37	45
Reason Not Completed
Lack of Efficacy	37	29	30	43
Adverse Event	4	4	3	1
Death	0	0	1	1
Withdrawal by Subject	3	1	0	0
No protocol therapy	2	5	1	0
others (not specified in the study)	0	2	2	0

Baseline Characteristics

Arm/Group Title		Arm I (12MP)	Arm II (12MP/Tet)	Arm III (12MP/6MHP)	Arm IV (6MHP)	Total
Arm/Group Description		Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Total of all reporting groups
Arm/Group Description		Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 (incomplete Freund's adjuvant) or Montanide ISA-51 VG (ISA-51) intradermally (ID) and subcutaneously (SC) on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection tetanus peptide melanoma vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising melanoma helper peptide vaccine (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection	Total of all reporting groups
Overall Number of Baseline Participants		41	33	32	42	148
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	41 participants	33 participants	32 participants	42 participants	148 participants
		65 (35 to 86)	69 (31 to 88)	66 (32 to 89)	64 (40 to 82)	66 (31 to 89)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	41 participants	33 participants	32 participants	42 participants	148 participants
	Female	18 43.9%	14 42.4%	11 34.4%	17 40.5%	60 40.5%
	Male	23 56.1%	19 57.6%	21 65.6%	25 59.5%	88 59.5%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	41 participants	33 participants	32 participants	42 participants	148 participants
United States		41	33	32	42	148

Outcome Measures

1.Primary Outcome


Title	Cytotoxic T-cell Lymphocytes (CTL) Response Rate
Description	Assessment of CTL response was based on a fold-increase in T cell resp...
Description	Assessment of CTL response was based on a fold-increase in T cell response measure by interferon-gamma ELIspot assay.
Time Frame	Immune response was assessed at pre-registrtion, in weeks 1, 3, 5, 7, 8

Outcome Measure Data

Analysis Population Description

140 eligible and treated patients who had CTL response data were included in the analysis


Arm/Group Title	Arm I (12MP)	Arm II (12MP/Tet)	Arm III (12MP/6MHP)	Arm IV (6MHP)
Arm/Group Description:	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...
Arm/Group Description:	Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 (incomplete Freund's adjuvant) or Montanide ISA-51 VG (ISA-51) intradermally (ID) and subcutaneously (SC) on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection tetanus peptide melanoma vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising melanoma helper peptide vaccine (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection
Overall Number of Participants Analyzed	40	30	29	41
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	43 (27 to 59)	47 (28 to 66)	28 (13 to 47)	5 (0.6 to 16.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (12MP), Arm II (12MP/Tet), Arm III (12MP/6MHP), Arm IV (6MHP)
	Comments	Compare CTL response rate among four arms. The null hypothesis is that CTL response is same in all four arms. Alternative hypothesis is that CTL response rate is different in at least one arm compared to other arms.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

2.Secondary Outcome


Title	Helper T-cells Response to 6MHP
Description	Helper T cell response was evaluated by tritiated thymidine proliferat...
Description	Helper T cell response was evaluated by tritiated thymidine proliferation assay with fresh/cryopreserved PBL in the presence of each of the helper peptides.
Time Frame	Immune response was assessed at pre-registration, in weeks 1,3,5,7,8

Outcome Measure Data

Analysis Population Description

128 eligible and treated patients who had data about helper T cell response were included in the analysis


Arm/Group Title	Arm I (12MP)	Arm II (12MP/Tet)	Arm III (12MP/6MHP)	Arm IV (6MHP)
Arm/Group Description:	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...
Arm/Group Description:	Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 (incomplete Freund's adjuvant) or Montanide ISA-51 VG (ISA-51) intradermally (ID) and subcutaneously (SC) on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection tetanus peptide melanoma vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising melanoma helper peptide vaccine (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection
Overall Number of Participants Analyzed	37	27	25	39
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	3 (0 to 14)	0 (0 to 13)	40 (21 to 61)	41 (26 to 58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (12MP), Arm II (12MP/Tet), Arm III (12MP/6MHP), Arm IV (6MHP)
	Comments	Compare HTL response rate to 6MHP among four arms. The null hypothesis is that HTL response is same in all four arms. Alternative hypothesis is that HTL response rate is different in at least one arm compared to other arms.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

3.Secondary Outcome


Title	Helper T Cell Response to Tetanus
Description	Helper T cell response was evaluated by tritiated thymidine proliferat...
Description	Helper T cell response was evaluated by tritiated thymidine proliferation assay with fresh/cryopreserved PBL in the presence of each of the helper peptides.
Time Frame	Immune response was assessed at pre-registration, in weeks 1,3,5,7,8

Outcome Measure Data

Analysis Population Description

128 eligible and treated patients who had data about HTL response to tetanus peptide were included in the analysis


Arm/Group Title	Arm I (12MP)	Arm II (12MP/Tet)	Arm III (12MP/6MHP)	Arm IV (6MHP)
Arm/Group Description:	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...
Arm/Group Description:	Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 (incomplete Freund's adjuvant) or Montanide ISA-51 VG (ISA-51) intradermally (ID) and subcutaneously (SC) on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection tetanus peptide melanoma vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising melanoma helper peptide vaccine (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection
Overall Number of Participants Analyzed	37	27	25	39
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	11 (3 to 25)	59 (39 to 79)	4 (0 to 20)	0 (0 to 9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (12MP), Arm II (12MP/Tet), Arm III (12MP/6MHP), Arm IV (6MHP)
	Comments	Compare HTL response rate to tetanus peptide among four arms. The null hypothesis is that HTL response is same in all four arms. Alternative hypothesis is that HTL response rate is different in at least one arm compared to other arms.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

4.Secondary Outcome


Title	Objective Response Rate
Description	Tumor response was assessed via Response Evaluation Criteria in Solid ...
Description	Tumor response was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Objective response rate is calculated as the number of patients with complete response (disappearance of all lesions) or partial response () divided by total number of evaluable patients.
Time Frame	Tumor response was assessed in weeks 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, and 6 months after last vaccination

Outcome Measure Data

Analysis Population Description

148 eligible and treated patients were included in the analysis


Arm/Group Title	Arm I (12MP)	Arm II (12MP/Tet)	Arm III (12MP/6MHP)	Arm IV (6MHP)
Arm/Group Description:	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...
Arm/Group Description:	Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 (incomplete Freund's adjuvant) or Montanide ISA-51 VG (ISA-51) intradermally (ID) and subcutaneously (SC) on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection tetanus peptide melanoma vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising melanoma helper peptide vaccine (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection
Overall Number of Participants Analyzed	41	33	32	42
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	2.4 (0.06 to 12.8)	3.0 (0.08 to 15.8)	6.3 (0.8 to 20.8)	7.1 (1.5 to 19.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (12MP), Arm II (12MP/Tet), Arm III (12MP/6MHP), Arm IV (6MHP)
	Comments	Compare objective response rate among four arms. The null hypothesis is that objective response rate is same in all four arms. Alternative hypothesis is that objective response rate is different in at least one arm compared to other arms.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.741
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

5.Secondary Outcome


Title	Median Overall Survival (OS)
Description	OS was defined as the time from registration to death from any cause.
Description	OS was defined as the time from registration to death from any cause.
Time Frame	assessed every 3 month within 2 years and every 6 months betwen 2 and 5 years

Outcome Measure Data

Analysis Population Description

148 eligible and treated patients were included in the analysis


Arm/Group Title	Arm I (12MP)	Arm II (12MP/Tet)	Arm III (12MP/6MHP)	Arm IV (6MHP)
Arm/Group Description:	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...
Arm/Group Description:	Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 (incomplete Freund's adjuvant) or Montanide ISA-51 VG (ISA-51) intradermally (ID) and subcutaneously (SC) on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection tetanus peptide melanoma vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising melanoma helper peptide vaccine (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection
Overall Number of Participants Analyzed	41	33	32	42
Median (95% Confidence Interval) Unit of Measure: months
	14.9 (10.1 to 18.6)	10.2 (6.7 to 12.2)	12.4 (4.8 to 16.8)	11.1 (8.8 to 14.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (12MP), Arm II (12MP/Tet), Arm III (12MP/6MHP), Arm IV (6MHP)
	Comments	Compare overall survival curves among four arms.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.532
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Adverse Events

Time Frame	Assessed at the end of each cycle while on treatment and at 30 days following the last dose of treatment. Reported every 3 months within 2 years of study entry, and every 6 months between 2-5 years of study entry
Adverse Event Reporting Description	All patients who received protocol therapy were evaluated for toxicity, regardless of eligibility.

Arm/Group Title	Arm I (12MP)	Arm II (12MP/Tet)	Arm III (12MP/6MHP)	Arm IV (6MHP)
Arm/Group Description	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...	Patients receive 2 injections of mu...
Arm/Group Description	Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 (incomplete Freund's adjuvant) or Montanide ISA-51 VG (ISA-51) intradermally (ID) and subcutaneously (SC) on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection tetanus peptide melanoma vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. multi-epitope melanoma peptide vaccine : Given by injection incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection	Patients receive 2 injections of multi-epitope peptide vaccine comprising melanoma helper peptide vaccine (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7. incomplete Freund's adjuvant : Given by injection sargramostim : Given by injection melanoma helper peptide vaccine : Given by injection
All-Cause Mortality
	Arm I (12MP)	Arm II (12MP/Tet)	Arm III (12MP/6MHP)	Arm IV (6MHP)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Arm I (12MP)	Arm II (12MP/Tet)	Arm III (12MP/6MHP)	Arm IV (6MHP)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	6/45 (13.33%)	9/38 (23.68%)	6/36 (16.67%)	4/48 (8.33%)
Blood and lymphatic system disorders
Anemia ^† 1	0/45 (0.00%)	0/38 (0.00%)	0/36 (0.00%)	1/48 (2.08%)
Ear and labyrinth disorders
Tinnitus ^† 1	0/45 (0.00%)	0/38 (0.00%)	1/36 (2.78%)	0/48 (0.00%)
Gastrointestinal disorders
Nausea ^† 1	0/45 (0.00%)	0/38 (0.00%)	1/36 (2.78%)	0/48 (0.00%)
Vomiting ^† 1	0/45 (0.00%)	0/38 (0.00%)	1/36 (2.78%)	0/48 (0.00%)
Abdomen, pain ^† 1	0/45 (0.00%)	0/38 (0.00%)	1/36 (2.78%)	0/48 (0.00%)
General disorders
Fatigue ^† 1	0/45 (0.00%)	4/38 (10.53%)	5/36 (13.89%)	1/48 (2.08%)
Injection site reaction ^† 1	2/45 (4.44%)	3/38 (7.89%)	0/36 (0.00%)	2/48 (4.17%)
Immune system disorders
Allergic reaction ^† 1	0/45 (0.00%)	1/38 (2.63%)	0/36 (0.00%)	0/48 (0.00%)
Infections and infestations
Infection Gr0-2 neut, lung ^† 1	1/45 (2.22%)	0/38 (0.00%)	0/36 (0.00%)	0/48 (0.00%)
Infection Gr0-2 neut, skin ^† 1	1/45 (2.22%)	0/38 (0.00%)	0/36 (0.00%)	0/48 (0.00%)
Investigations
Leukopenia (Leukocytes decreased) ^† 1	1/45 (2.22%)	1/38 (2.63%)	0/36 (0.00%)	0/48 (0.00%)
Lymphopenia ^† 1	1/45 (2.22%)	1/38 (2.63%)	1/36 (2.78%)	0/48 (0.00%)
Neutropenia (Neutrophils decreased) ^† 1	1/45 (2.22%)	0/38 (0.00%)	0/36 (0.00%)	0/48 (0.00%)
Cardiac troponin I (cTnI) ^† 1	1/45 (2.22%)	0/38 (0.00%)	0/36 (0.00%)	0/48 (0.00%)
Alanine aminotransferase (ALT, SGPT) ^† 1	0/45 (0.00%)	0/38 (0.00%)	2/36 (5.56%)	0/48 (0.00%)
Aspartate aminotransferase (AST, SGOT) ^† 1	0/45 (0.00%)	0/38 (0.00%)	1/36 (2.78%)	0/48 (0.00%)
Blood bilirubin increased ^† 1	0/45 (0.00%)	0/38 (0.00%)	1/36 (2.78%)	0/48 (0.00%)
Metabolic/Laboratory-other ^† 1	0/45 (0.00%)	0/38 (0.00%)	1/36 (2.78%)	0/48 (0.00%)
Metabolism and nutrition disorders
Hyponatremia ^† 1	1/45 (2.22%)	0/38 (0.00%)	0/36 (0.00%)	0/48 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain ^† 1	0/45 (0.00%)	0/38 (0.00%)	1/36 (2.78%)	0/48 (0.00%)
Nervous system disorders
Central nervous system (CNS) cerebrovascular ischemia ^† 1	0/45 (0.00%)	1/38 (2.63%)	0/36 (0.00%)	0/48 (0.00%)
Head/headache ^† 1	0/45 (0.00%)	1/38 (2.63%)	0/36 (0.00%)	1/48 (2.08%)
Respiratory, thoracic and mediastinal disorders
Dyspnea ^† 1	0/45 (0.00%)	0/38 (0.00%)	1/36 (2.78%)	0/48 (0.00%)
Pneumonitis/pulmonary infiltrates ^† 1	1/45 (2.22%)	0/38 (0.00%)	0/36 (0.00%)	0/48 (0.00%)
Skin and subcutaneous tissue disorders
Ulceration ^† 1	0/45 (0.00%)	1/38 (2.63%)	1/36 (2.78%)	0/48 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE v3
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm I (12MP)	Arm II (12MP/Tet)	Arm III (12MP/6MHP)	Arm IV (6MHP)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	36/45 (80.00%)	28/38 (73.68%)	28/36 (77.78%)	33/48 (68.75%)
Gastrointestinal disorders
Constipation ^† 1	0/45 (0.00%)	1/38 (2.63%)	2/36 (5.56%)	1/48 (2.08%)
Diarrhea w/o prior colostomy ^† 1	3/45 (6.67%)	2/38 (5.26%)	1/36 (2.78%)	3/48 (6.25%)
Nausea ^† 1	1/45 (2.22%)	6/38 (15.79%)	3/36 (8.33%)	2/48 (4.17%)
Vomiting ^† 1	0/45 (0.00%)	2/38 (5.26%)	1/36 (2.78%)	1/48 (2.08%)
General disorders
Fatigue ^† 1	9/45 (20.00%)	11/38 (28.95%)	10/36 (27.78%)	7/48 (14.58%)
Fever w/o neutropenia ^† 1	1/45 (2.22%)	4/38 (10.53%)	2/36 (5.56%)	0/48 (0.00%)
Rigors/chills ^† 1	1/45 (2.22%)	5/38 (13.16%)	4/36 (11.11%)	2/48 (4.17%)
Injection site reaction ^† 1	28/45 (62.22%)	20/38 (52.63%)	18/36 (50.00%)	18/48 (37.50%)
Investigations
Leukopenia (Leukocytes decreased) ^† 1	3/45 (6.67%)	5/38 (13.16%)	1/36 (2.78%)	0/48 (0.00%)
Lymphopenia ^† 1	2/45 (4.44%)	8/38 (21.05%)	6/36 (16.67%)	4/48 (8.33%)
Neutropenia (Neutrophils decreased) ^† 1	0/45 (0.00%)	2/38 (5.26%)	0/36 (0.00%)	1/48 (2.08%)
Thrombocytopenia (Platelets decreased) ^† 1	2/45 (4.44%)	3/38 (7.89%)	2/36 (5.56%)	1/48 (2.08%)
Alkaline phosphatase increased ^† 1	4/45 (8.89%)	3/38 (7.89%)	2/36 (5.56%)	4/48 (8.33%)
Aspartate aminotransferase increased (AST, SGOT) ^† 1	3/45 (6.67%)	5/38 (13.16%)	2/36 (5.56%)	1/48 (2.08%)
Blood bilirubin increased ^† 1	1/45 (2.22%)	2/38 (5.26%)	2/36 (5.56%)	0/48 (0.00%)
Creatinine increased ^† 1	2/45 (4.44%)	3/38 (7.89%)	1/36 (2.78%)	5/48 (10.42%)
Metabolic/Laboratory-other ^† 1	2/45 (4.44%)	2/38 (5.26%)	5/36 (13.89%)	3/48 (6.25%)
Alanine aminotransferase increased (ALT, SGPT) ^† 1	2/45 (4.44%)	1/38 (2.63%)	2/36 (5.56%)	1/48 (2.08%)
Metabolism and nutrition disorders
Anorexia ^† 1	1/45 (2.22%)	3/38 (7.89%)	3/36 (8.33%)	2/48 (4.17%)
Hyponatremia ^† 1	0/45 (0.00%)	0/38 (0.00%)	2/36 (5.56%)	1/48 (2.08%)
Musculoskeletal and connective tissue disorders
Joint, pain ^† 1	2/45 (4.44%)	1/38 (2.63%)	1/36 (2.78%)	3/48 (6.25%)
Muscle, pain ^† 1	6/45 (13.33%)	1/38 (2.63%)	2/36 (5.56%)	1/48 (2.08%)
Nervous system disorders
Dizziness ^† 1	0/45 (0.00%)	2/38 (5.26%)	1/36 (2.78%)	0/48 (0.00%)
Head/headache ^† 1	5/45 (11.11%)	5/38 (13.16%)	3/36 (8.33%)	2/48 (4.17%)
Respiratory, thoracic and mediastinal disorders
Dyspnea ^† 1	1/45 (2.22%)	1/38 (2.63%)	2/36 (5.56%)	1/48 (2.08%)
Skin and subcutaneous tissue disorders
Sweating ^† 1	0/45 (0.00%)	3/38 (7.89%)	2/36 (5.56%)	1/48 (2.08%)
Pruritus/itching ^† 1	4/45 (8.89%)	2/38 (5.26%)	2/36 (5.56%)	2/48 (4.17%)
Rash/desquamation ^† 1	1/45 (2.22%)	2/38 (5.26%)	5/36 (13.89%)	1/48 (2.08%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE v3

Limitations and Caveats

[Not Specified]

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Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

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Name/Title:	Study Statistician
Organization:	Eastern Cooperative Oncology Group (ECOG) Statistical Office
Phone:	617-632-3012

Layout table for additonal information

Responsible Party:	Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00071981
Obsolete Identifiers:	NCT00464152
Other Study ID Numbers:	CDR0000335055 U10CA021115 ( U.S. NIH Grant/Contract ) E1602 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) )
First Submitted:	November 4, 2003
First Posted:	November 6, 2003
Results First Submitted:	November 24, 2012
Results First Posted:	January 3, 2013
Last Update Posted:	October 28, 2015

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