Peptide Vaccination for Patients at High Risk for Recurrent Melanoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00059475
• Collaborator: (none)
• Enrollment: 138
• Location: 1
• Arms: 8
• Duration (Months): 85
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

This study will examine the effectiveness and side effects of an experimental vaccine to prevent recurrence of melanoma. The likelihood of melanoma returning is higher in patients who have melanoma lesions deep in the skin, in patients who have had positive lymph nodes, and in patients who have had surgery for metastatic disease (cancer that has spread beyond the primary site). Melanoma tumors produce proteins called glycoprotein 100 (gp100) and melanoma-associated antigen recognized by T cells 1 (MART-1). Vaccination with specific pieces of these proteins (peptides) may boost the immune system's fight against the cancer. The vaccine injections are mixed with an oil-based substance called Montanide ISA-51, which is intended to increase the immune response to the peptide.

Patients 16 years of age and older whose melanoma has been surgically removed and who are currently free of disease may be eligible for this study. Candidates will be screened with a physical examination and blood and urine tests. An electrocardiogram (EKG), x-rays and other imaging studies will be done if recent results are not available. Some candidates may require heart tests, such as a cardiac stress test or echocardiogram, or lung function tests. In addition, all candidates will be tested for human leukocyte antigen (HLA) tissue type; patients must be type human leukocyte antigens (HLA-A)*0201, the type on which this vaccine is based.

Participants will be randomly assigned to receive one of four different vaccines to determine which peptides offer the best immunity. Each treatment course consists of two injections of the vaccines every 3 weeks for four times. The injections are given under the skin of the thigh. After every other treatment course (every 6 months), patients will undergo a series of x-rays and scans to look for tumor. The immunizations may continue for up to 12 months as long as the melanoma does not return. The injections are given at the National Institutes of Health (NIH) Clinical Center. Patients are monitored for 1 hour after each injection and have blood tests and a physical examination to look for treatment side effects.

Patients will be followed with blood tests every 12 weeks to monitor body functions. They will also undergo leukapheresis-a procedure to collect white blood cells-before starting treatment and about 3 to 4 weeks after the fourth vaccine to evaluate how the vaccines affect the action of the immune system cells. For this procedure, blood is drawn through a needle in the arm, similar to donating blood. The blood goes through a machine that separates out the lymphocytes (white blood cells), and the rest of the blood is returned through a needle in the other arm. Some patients may undergo a biopsy-surgical removal of a small piece of tissue under local anesthetic-of normal skin and tumor or lymph node tissue to examine the effects of the vaccines on the tumor immune cells.

Patients whose disease returns during the first course of vaccine therapy will have surgery to remove the tumor and will continue to receive the vaccine treatment. Patients whose tumor returns after completing one course of therapy may receive a substance called interleukin-2 (IL-2), which can boost immune function against the tumor. interleukin-2 (IL-2) is given intravenously (through a small tube placed in a vein) every 8 hours for 4 days. This regimen is repeated after 10 to 14 days. Those who respond to interleukin-2 (IL-2) will have a third course of treatment after 2 months. Patients whose disease recurs after treatment will be taken off the study and will be referred back to their referring physician or to another study, if an appropriate one is available.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Drug: Glycoprotein 100 (GP100): 209-217 (210M); Drug: Interleukin-2 (IL-2); Drug: Montanide ISA 51; Drug: Melanoma antigen recognized by T-cells (MART)-1: 27-35; Drug: 27-35 (27L): melanoma antigen recognized by T-cells (MART)-1; Drug: melanoma antigen recognized by T-cells (MART)-1: 26-35(27L)	Phase 2

Detailed Description

Human leukocyte antigens (HLA-A)*0201 positive patients at high risk for recurrence of melanoma, or completely resected metastatic melanoma will receive immunization with peptides representing human leukocyte antigen (HLA)-restricted T cell epitopes of the melanoma antigen recognized by T-cells (MART-1) or glycoprotein 100 (gp100) melanoma antigens emulsified in Montanide ISA-51 or Montanide trademark(TM) ISA 51 vegetable grade (VG). Patients will be randomized to receive one of three different melanoma antigen recognized by T-cells (MART-1) peptides or to receive a combination of a melanoma antigen recognized by T-cells (MART-1) peptide plus a glycoprotein 100 (gp100) peptide. This study is designed to evaluate the immunologic effects of the different peptide immunizations.

Study Design

• Study Type: Interventional
• Actual Enrollment: 138 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Comparison of Peptide Immunization in Patients at High Risk for Recurrence of Melanoma
• Study Start Date: Apr 1, 2003
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adj-2 MART-1: 27-35 melanoma antigen recognized by T-cells (MART)-1:27-35 peptide every three weeks for four cycles (Arm I).	Drug: Montanide ISA 51; Drug: Melanoma antigen recognized by T-cells (MART)-1: 27-35
Experimental: Adj-2 HD IL-2 after MART-1: 27-35 High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm I (Arm IA)	Drug: Interleukin-2 (IL-2); 720,000 IU/kg as an intravenous bolus over a 15 minute period every 8 hours and continuing for up to 4 days (a maximum of 12 doses).; Other Names: Interleukin-2 ; Drug: Montanide ISA 51; Drug: Melanoma antigen recognized by T-cells (MART)-1: 27-35
Experimental: Adj-2 27-35 (27L) MART-1 (Mod9mer) peptide Q3wks x 4 27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide every three weeks for four cycles (Arm II).	Drug: Montanide ISA 51; Drug: 27-35 (27L): melanoma antigen recognized by T-cells (MART)-1
Experimental: Adj-2 HD IL-2 after 27-35 (27L): MART-1 (Mod9mer) High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm II (Arm IIA)	Drug: Interleukin-2 (IL-2); 720,000 IU/kg as an intravenous bolus over a 15 minute period every 8 hours and continuing for up to 4 days (a maximum of 12 doses).; Other Names: Interleukin-2 ; Drug: Montanide ISA 51; Drug: 27-35 (27L): melanoma antigen recognized by T-cells (MART)-1
Experimental: Adj-2 MART-1: 26-35 (27L) (Mod10mer) peptide Q3wks x 4 melanoma antigen recognized by T-cells (MART)-1:26-35(27L) peptide every three weeks for four cycles (Arm III).	Drug: Montanide ISA 51; Drug: melanoma antigen recognized by T-cells (MART)-1: 26-35(27L)
Experimental: Adj-2 HD IL-2 after MART-1: 26-35 (27L) (Mod10mer) High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm III (Arm IIIA)	Drug: Interleukin-2 (IL-2); 720,000 IU/kg as an intravenous bolus over a 15 minute period every 8 hours and continuing for up to 4 days (a maximum of 12 doses).; Other Names: Interleukin-2 ; Drug: Montanide ISA 51; Drug: melanoma antigen recognized by T-cells (MART)-1: 26-35(27L)
Experimental: Adj-2 27-35 (27L): MART-1 + gp100: 209-217 (210M) Q3wks x 4 27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide plus the gp100:209-217(210M) peptide emulsified together every three weeks for four cycles (Arm IV).	Drug: Glycoprotein 100 (GP100): 209-217 (210M); Drug: Montanide ISA 51; Drug: 27-35 (27L): melanoma antigen recognized by T-cells (MART)-1
Experimental: Adj-2 HD IL-2 after 27-35 (27L): MART-1 + gp209-2M High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm IV (Arm IVA)	Drug: Interleukin-2 (IL-2); 720,000 IU/kg as an intravenous bolus over a 15 minute period every 8 hours and continuing for up to 4 days (a maximum of 12 doses).; Other Names: Interleukin-2 ; Drug: Montanide ISA 51; Drug: 27-35 (27L): melanoma antigen recognized by T-cells (MART)-1

Outcome Measures

Primary Outcome Measures

1. Immunologic Response Rate [11 months]

   Immunologic monitoring will be conducted using in vitro sensitization assays. The immunologic response in these assays will be considered positive if at least a two-fold increase in vaccine specific interferon gamma (y-IFN) secretion is seen between post vaccination specimens compared to the pre vaccination specimens.

2. Response Rate [6 years]

   Response is measured from the time measurement criteria are first met for complete response (CR) or partial response (PR) (whichever is first) until the first date that recurrent disease is objectively documented. Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.

Secondary Outcome Measures

1. Number of Participants With Adverse Events [11 months]

   Here are the number of participants with adverse events. For details about the adverse events see the adverse event module.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

Human leukocyte antigens (HLA-A)*0201 patients, age greater than or equal to 16 years, with lesions greater than or equal to 1.5 mm in thickness, or greater than or equal to 1 positive lymph node, or ulcerated lesions, or local recurrence, or completely resected metastatic melanoma, within 6 months of surgical resection will be considered. Patients must be clinically disease free at the time of protocol entry as documented by radiologic studies within 6 weeks of patient entry.

Serum creatinine of 2.0 mg/dl or less.

Total bilirubin 1.6 mg/dl or less, except for patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

White blood cell (WBC) 3000/mm^3 or greater.

Platelet count 90,000 mm^3 or greater.

Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than three times normal.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Patients of both genders must be willing to practice effective birth control during this trial because the potential for teratogenic effects are unknown.

Patients may have had prior adjuvant treatment with immunotherapy, including interferon, or may have had treatment for metastatic disease and are now no evidence of disease (NED), including chemotherapy or biotherapy, as long as 3 weeks have elapsed since prior systemic therapy.

EXCLUSION CRITERIA:

Patients will be excluded:

1. who have ocular or mucosal melanoma.

2. who are undergoing or have undergone in the past 3 weeks any systemic therapy except surgery for their cancer, and must have recovered from any adverse effects of treatment prior to entry, other than those that do not have clinical implications, e.g. vitiligo, alopecia.

3. have active systemic infections, autoimmune disease or any known immunodeficiency disease.

4. who require systemic steroid therapy.

5. who are pregnant or breastfeeding.

6. who are known to be positive for hepatitis B surface antigen (B(s)AG) or human immunodeficiency virus (HIV) antibody.

7. who have any form of active primary or secondary immunodeficiency or who have not recovered immune competence after chemotherapy or radiation therapy.

8. who have previously been immunized with melanoma antigen recognized by T-cells (MART)-1.

9. who have known hypersensitivity to any of the agents used in this study.

ELIGIBILITY FOR ADMINISTRATION OF Interleukin-2 (IL-2):

Patients who develop progressive disease while receiving peptide alone must meet the following criteria to be eligible to receive Interleukin-2 (IL-2):

1. Patients must have measurable metastatic melanoma.

2. Patients may not have active major medical illnesses such as cardiac ischemia, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.

3. Patients with recent prolonged history of cigarette smoking or symptoms of respiratory dysfunction must have a normal pulmonary function test as evidenced by a forced expiratory volume 1 (FEV 1) greater than 60% predicted.

4. Patients with electrocardiogam (EKG) abnormalities, symptoms of cardiac ischemia or arrhythmias or age greater than 50 years will have a normal stress cardiac test (stress thallium, stress multi-gated acquisition scan (MUGA), dobutamine echocardiogram or other stress test).

5. Patients must be willing to sign a durable power of attorney (DPA).

6. Serum creatinine of 2.0 mg/dl or less.

7. Total bilirubin 2.0 mg/dl or less, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

8. White blood cell (WBC) 3000/mm^3 or greater.

9. Platelet count 90,000 mm^3 or greater.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Cancer Institute (NCI)	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Steven A Rosenberg, M.D., National Cancer Institute, National Institutes of Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9.

• Responsible Party: Steven Rosenberg, Dr. Steven Rosenberg, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00059475
• Other Study ID Numbers: 030172; 03-C-0172; NCT00062218
• First Posted: Apr 28, 2003
• Last Update Posted: Oct 23, 2012
• Last Verified: Oct 1, 2012

• Keywords provided by Steven Rosenberg, Dr. Steven Rosenberg, National Institutes of Health Clinical Center (CC): Adjuvant Therapy; MART-1 Peptides; GP100 Peptide; Immunologic Response; Melanoma
• Additional relevant MeSH terms: Melanoma; polysaccharide-K; Interleukin-2; Monatide (IMS 3015)

Study Results

Participant Flow

Recruitment Details	subjects were accrued to this trial.

Arm/Group Title	Adj-2 MART-1: 27-35	Adj-2 HD IL-2 After MART-1: 27-35	Adj-2 27-35 (27L) MART-1 (Mod9mer) Peptide Q3wks x 4	Adj-2 HD IL-2 After 27-35 (27L): MART-1 (Mod9mer)	Adj-2 MART-1: 26-35 (27L) (Mod10mer) Peptide Q3wks x 4	Adj-2 HD IL-2 After MART-1: 26-35 (27L) (Mod10mer)	Adj-2 27-35 (27L): MART-1 + gp100: 209-217 (210M) Q3wks x 4	Adj-2 HD IL-2 After 27-35 (27L): MART-1 + gp209-2M
Arm/Group Description	melanoma antigen recognized by T-cells (MART)-1:27-35 peptide every three weeks for four cycles (Arm I).	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm I (Arm IA)	27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide every three weeks for four cycles (Arm II).	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm II (Arm IIA)	melanoma antigen recognized by T-cells (MART)-1:26-35(27L) peptide every three weeks for four cycles (Arm III).	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm III (Arm IIIA)	27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide plus the gp100:209-217(210M) peptide emulsified together every three weeks for four cycles (Arm IV).	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm IV (Arm IVA)
Period Title: Overall Study
STARTED	33	2	24	3	33	2	34	7
COMPLETED	33	2	24	3	33	2	34	7
NOT COMPLETED	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Adj-2 MART-1: 27-35	Adj-2 HD IL-2 After MART-1: 27-35	Adj-2 27-35 (27L) MART-1 (Mod9mer) Peptide Q3wks x 4	Adj-2 HD IL-2 After 27-35 (27L): MART-1 (Mod9mer)	Adj-2 MART-1: 26-35 (27L) (Mod10mer) Peptide Q3wks x 4	Adj-2 HD IL-2 After MART-1: 26-35 (27L) (Mod10mer)	Adj-2 27-35 (27L): MART-1 + gp100: 209-217 (210M) Q3wks x 4	Adj-2 HD IL-2 After 27-35 (27L): MART-1 + gp209-2M	Total
Arm/Group Description	melanoma antigen recognized by T-cells (MART)-1:27-35 peptide every three weeks for four cycles (Arm I).	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm I (Arm IA)	27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide every three weeks for four cycles (Arm II).	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm II (Arm IIA)	melanoma antigen recognized by T-cells (MART)-1:26-35(27L) peptide every three weeks for four cycles (Arm III).	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm III (Arm IIIA)	27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide plus the gp100:209-217(210M) peptide emulsified together every three weeks for four cycles (Arm IV).	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm IV (Arm IVA)	Total of all reporting groups
Overall Participants	33	2	24	3	33	2	34	7	138
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.9%	0 0%	1 0.7%
Between 18 and 65 years	30 90.9%	2 100%	20 83.3%	3 100%	29 87.9%	2 100%	33 97.1%	7 100%	126 91.3%
>=65 years	3 9.1%	0 0%	4 16.7%	0 0%	4 12.1%	0 0%	0 0%	0 0%	11 8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.8 (14.9)	42.0 (8.5)	48.5 (12.9)	52.7 (3.8)	47.5 (13.0)	52.0 (8.5)	44.9 (11.4)	48.0 (8.5)	47.55 (10.18)
Sex: Female, Male (Count of Participants)
Female	13 39.4%	2 100%	6 25%	0 0%	14 42.4%	0 0%	15 44.1%	4 57.1%	54 39.1%
Male	20 60.6%	0 0%	18 75%	3 100%	19 57.6%	2 100%	19 55.9%	3 42.9%	84 60.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	1 3%	0 0%	0 0%	0 0%	1 0.7%
Not Hispanic or Latino	33 100%	2 100%	24 100%	3 100%	32 97%	2 100%	34 100%	7 100%	137 99.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	1 4.2%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%
White	33 100%	2 100%	23 95.8%	3 100%	33 100%	2 100%	34 100%	7 100%	137 99.3%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	33 100%	2 100%	24 100%	3 100%	33 100%	2 100%	34 100%	7 100%	138 100%

Outcome Measures

1. Primary Outcome

Title	Immunologic Response Rate
Description	Immunologic monitoring will be conducted using in vitro sensitization assays. The immunologic response in these assays will be considered positive if at least a two-fold increase in vaccine specific interferon gamma (y-IFN) secretion is seen between post vaccination specimens compared to the pre vaccination specimens.
Time Frame	11 months

Outcome Measure Data

Analysis Population Description

The number of participants analyzed and results are correct. We do not have the immunologic response rate data for all patients.

Arm/Group Title	Adj-2 MART-1: 27-35	Adj-2 27-35 (27L) MART-1 (Mod9mer) Peptide Q3wks x 4	Adj-2 MART-1: 26-35 (27L) (Mod10mer) Peptide Q3wks x 4	Adj-2 27-35 (27L): MART-1 + gp100: 209-217 (210M) Q3wks x 4
Arm/Group Description	melanoma antigen recognized by T-cells (MART)-1:27-35 peptide every three weeks for four cycles (Arm I).	27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide every three weeks for four cycles (Arm II).	melanoma antigen recognized by T-cells (MART)-1:26-35(27L) peptide every three weeks for four cycles (Arm III).	27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide plus the gp100:209-217(210M) peptide emulsified together every three weeks for four cycles (Arm IV).
Measure Participants	13	13	13	8
Number [Participants]	7 21.2%	1 50%	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Here are the number of participants with adverse events. For details about the adverse events see the adverse event module.
Time Frame	11 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adj-2 MART-1: 27-35	Adj-2 HD IL-2 After MART-1: 27-35	Adj-2 27-35 (27L) MART-1 (Mod9mer) Peptide Q3wks x 4	Adj-2 HD IL-2 After 27-35 (27L): MART-1 (Mod9mer)	Adj-2 MART-1: 26-35 (27L) (Mod10mer) Peptide Q3wks x 4	Adj-2 HD IL-2 After MART-1: 26-35 (27L) (Mod10mer)	Adj-2 27-35 (27L): MART-1 + gp100: 209-217 (210M) Q3wks x 4	Adj-2 HD IL-2 After 27-35 (27L): MART-1 + gp209-2M
Arm/Group Description	melanoma antigen recognized by T-cells (MART)-1:27-35 peptide every three weeks for four cycles (Arm I).	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm I (Arm IA)	27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide every three weeks for four cycles (Arm II).	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm II (Arm IIA)	melanoma antigen recognized by T-cells (MART)-1:26-35(27L) peptide every three weeks for four cycles (Arm III).	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm III (Arm IIIA)	27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide plus the gp100:209-217(210M) peptide emulsified together every three weeks for four cycles (Arm IV).	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm IV (Arm IVA)
Measure Participants	33	2	24	3	33	2	34	7
Number [Participants]	31 93.9%	2 100%	20 83.3%	3 100%	32 97%	2 100%	30 88.2%	7 100%

3. Primary Outcome

Title	Response Rate
Description	Response is measured from the time measurement criteria are first met for complete response (CR) or partial response (PR) (whichever is first) until the first date that recurrent disease is objectively documented. Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

The number of participants analyzed and results are correct. We do not have the response rate data for all patients.

Arm/Group Title	Adj-2 HD IL-2 After MART-1: 27-35	Adj-2 HD IL-2 After 27-35 (27L): MART-1 (Mod9mer)	Adj-2 HD IL-2 After MART-1: 26-35 (27L) (Mod10mer)	Adj-2 HD IL-2 After 27-35 (27L): MART-1 + gp209-2M
Arm/Group Description	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm I (Arm IA)	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm II (Arm IIA)	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm III (Arm IIIA)	High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm IV (Arm IVA)
Measure Participants	2	3	2	7
Number [participants]	1 3%	1 50%	0 0%	1 33.3%

Adverse Events

Arm/Group Title	Adj-2 MART-1: 27-35		Adj-2 HD IL-2 After MART-1: 27-35		Adj-2 27-35 (27L) MART-1 (Mod9mer) Peptide Q3wks x 4		Adj-2 HD IL-2 After 27-35 (27L): MART-1 (Mod9mer)		Adj-2 MART-1: 26-35 (27L) (Mod10mer) Peptide Q3wks x 4		Adj-2 HD IL-2 After MART-1: 26-35 (27L) (Mod10mer)		Adj-2 27-35 (27L): MART-1 + gp100: 209-217 (210M) Q3wks x 4		Adj-2 HD IL-2 After 27-35 (27L): MART-1 + gp209-2M
Arm/Group Description	melanoma antigen recognized by T-cells (MART)-1:27-35 peptide every three weeks for four cycles (Arm I).		High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm I (Arm IA)		27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide every three weeks for four cycles (Arm II).		High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm II (Arm IIA)		melanoma antigen recognized by T-cells (MART)-1:26-35(27L) peptide every three weeks for four cycles (Arm III).		High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm III (Arm IIIA)		27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide plus the gp100:209-217(210M) peptide emulsified together every three weeks for four cycles (Arm IV).		High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm IV (Arm IVA)
All Cause Mortality
	Adj-2 MART-1: 27-35		Adj-2 HD IL-2 After MART-1: 27-35		Adj-2 27-35 (27L) MART-1 (Mod9mer) Peptide Q3wks x 4		Adj-2 HD IL-2 After 27-35 (27L): MART-1 (Mod9mer)		Adj-2 MART-1: 26-35 (27L) (Mod10mer) Peptide Q3wks x 4		Adj-2 HD IL-2 After MART-1: 26-35 (27L) (Mod10mer)		Adj-2 27-35 (27L): MART-1 + gp100: 209-217 (210M) Q3wks x 4		Adj-2 HD IL-2 After 27-35 (27L): MART-1 + gp209-2M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	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)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Adj-2 MART-1: 27-35		Adj-2 HD IL-2 After MART-1: 27-35		Adj-2 27-35 (27L) MART-1 (Mod9mer) Peptide Q3wks x 4		Adj-2 HD IL-2 After 27-35 (27L): MART-1 (Mod9mer)		Adj-2 MART-1: 26-35 (27L) (Mod10mer) Peptide Q3wks x 4		Adj-2 HD IL-2 After MART-1: 26-35 (27L) (Mod10mer)		Adj-2 27-35 (27L): MART-1 + gp100: 209-217 (210M) Q3wks x 4		Adj-2 HD IL-2 After 27-35 (27L): MART-1 + gp209-2M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	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	0/33 (0%)		0/2 (0%)		0/24 (0%)		0/3 (0%)		0/33 (0%)		1/2 (50%)		0/34 (0%)		0/7 (0%)
Cardiac disorders
Nodal arrhythmia	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	1/2 (50%)	1	0/34 (0%)	0	0/7 (0%)	0
Cardiac troponin I increased	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	1/2 (50%)	1	0/34 (0%)	0	0/7 (0%)	0
Metabolism and nutrition disorders
Creatine phosphokinase increased	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	1/2 (50%)	1	0/34 (0%)	0	0/7 (0%)	0
Other (Not Including Serious) Adverse Events
	Adj-2 MART-1: 27-35		Adj-2 HD IL-2 After MART-1: 27-35		Adj-2 27-35 (27L) MART-1 (Mod9mer) Peptide Q3wks x 4		Adj-2 HD IL-2 After 27-35 (27L): MART-1 (Mod9mer)		Adj-2 MART-1: 26-35 (27L) (Mod10mer) Peptide Q3wks x 4		Adj-2 HD IL-2 After MART-1: 26-35 (27L) (Mod10mer)		Adj-2 27-35 (27L): MART-1 + gp100: 209-217 (210M) Q3wks x 4		Adj-2 HD IL-2 After 27-35 (27L): MART-1 + gp209-2M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	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	31/33 (93.9%)		2/2 (100%)		20/24 (83.3%)		3/3 (100%)		32/33 (97%)		2/2 (100%)		30/34 (88.2%)		7/7 (100%)
Blood and lymphatic system disorders
Platelet count decreased	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	1/3 (33.3%)	1	0/33 (0%)	0	0/2 (0%)	0	0/34 (0%)	0	0/7 (0%)	0
Cardiac disorders
Sinus tachycardia	0/33 (0%)	0	1/2 (50%)	2	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	1/2 (50%)	1	0/34 (0%)	0	1/7 (14.3%)	2
Ventricular arrhythmia	0/33 (0%)	0	1/2 (50%)	1	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	0/2 (0%)	0	0/34 (0%)	0	0/7 (0%)	0
Chest pain	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	1/3 (33.3%)	1	0/33 (0%)	0	0/2 (0%)	0	0/34 (0%)	0	0/7 (0%)	0
Gastrointestinal disorders
Diarrhea	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	0/3 (0%)	0	3/33 (9.1%)	3	0/2 (0%)	0	1/34 (2.9%)	1	1/7 (14.3%)	2
Nausea	0/33 (0%)	0	0/2 (0%)	0	1/24 (4.2%)	1	0/3 (0%)	0	2/33 (6.1%)	2	0/2 (0%)	0	2/34 (5.9%)	2	0/7 (0%)	0
Vomiting	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	0/3 (0%)	0	1/33 (3%)	1	0/2 (0%)	0	1/34 (2.9%)	1	0/7 (0%)	0
General disorders
Chills	2/33 (6.1%)	2	0/2 (0%)	0	1/24 (4.2%)	1	0/3 (0%)	0	1/33 (3%)	1	0/2 (0%)	0	0/34 (0%)	0	0/7 (0%)	0
Fatigue	3/33 (9.1%)	3	1/2 (50%)	1	1/24 (4.2%)	1	1/3 (33.3%)	1	4/33 (12.1%)	6	0/2 (0%)	0	4/34 (11.8%)	5	4/7 (57.1%)	5
Anticipated Dose Limiting Toxicity	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	0/2 (0%)	0	0/34 (0%)	0	1/7 (14.3%)	1
Metabolism and nutrition disorders
Alanine aminotransferase increased	0/33 (0%)	0	1/2 (50%)	1	0/24 (0%)	0	0/3 (0%)	0	1/33 (3%)	1	0/2 (0%)	0	0/34 (0%)	0	0/7 (0%)	0
Aspartate aminotransferase increased	0/33 (0%)	0	1/2 (50%)	1	0/24 (0%)	0	0/3 (0%)	0	1/33 (3%)	1	0/2 (0%)	0	0/34 (0%)	0	0/7 (0%)	0
Bilirubin increased	0/33 (0%)	0	1/2 (50%)	1	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	0/2 (0%)	0	0/34 (0%)	0	1/7 (14.3%)	1
Creatinine increased	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	2/3 (66.7%)	5	0/33 (0%)	0	0/2 (0%)	0	0/34 (0%)	0	2/7 (28.6%)	5
Musculoskeletal and connective tissue disorders
Myalgia	2/33 (6.1%)	2	0/2 (0%)	0	2/24 (8.3%)	2	0/3 (0%)	0	4/33 (12.1%)	6	0/2 (0%)	0	2/34 (5.9%)	2	0/7 (0%)	0
Joint pain	0/33 (0%)	0	1/2 (50%)	2	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	0/2 (0%)	0	0/34 (0%)	0	0/7 (0%)	0
Nervous system disorders
Confusion	0/33 (0%)	0	1/2 (50%)	2	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	2/2 (100%)	2	0/34 (0%)	0	4/7 (57.1%)	4
Psychiatric disorders
Depression	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	0/2 (0%)	0	0/34 (0%)	0	0/7 (0%)	0
Renal and urinary disorders
Low urine output	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	0/2 (0%)	0	0/34 (0%)	0	1/7 (14.3%)	2
Reproductive system and breast disorders
Abdominal pain	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	0/2 (0%)	0	0/34 (0%)	0	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/33 (0%)	0	0/2 (0%)	0	0/24 (0%)	0	0/3 (0%)	0	0/33 (0%)	0	0/2 (0%)	0	0/34 (0%)	0	1/7 (14.3%)	1
Skin and subcutaneous tissue disorders
Sweating	1/33 (3%)	1	0/2 (0%)	0	0/24 (0%)	0	0/3 (0%)	0	1/33 (3%)	1	0/2 (0%)	0	0/34 (0%)	0	0/7 (0%)	0
Injection site reaction	31/33 (93.9%)	90	0/2 (0%)	0	20/24 (83.3%)	66	0/3 (0%)	0	32/33 (97%)	94	0/2 (0%)	0	29/34 (85.3%)	89	0/7 (0%)	0
Pruritis	3/33 (9.1%)	3	0/2 (0%)	0	4/24 (16.7%)	6	0/3 (0%)	0	2/33 (6.1%)	2	0/2 (0%)	0	5/34 (14.7%)	5	0/7 (0%)	0
Rash desquamating	4/33 (12.1%)	4	0/2 (0%)	0	5/24 (20.8%)	5	0/3 (0%)	0	5/33 (15.2%)	6	0/2 (0%)	0	7/34 (20.6%)	8	1/7 (14.3%)	1
Vascular disorders
Hypotension	0/33 (0%)	0	1/2 (50%)	4	0/24 (0%)	0	1/3 (33.3%)	1	0/33 (0%)	0	0/2 (0%)	0	0/34 (0%)	0	3/7 (42.9%)	3

Limitations/Caveats

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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.