Vaccine Therapy in Treating Patients With Stage IIC-IV Melanoma

Phase 2

Completed

• Conditions: Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage IIIC Melanoma; Ciliary Body and Choroid Melanoma, Small Size; Stage IIIA Melanoma; Stage IIIB Intraocular Melanoma; Extraocular Extension Melanoma; Iris Melanoma; Ciliary Body and Choroid Melanoma, Medium/Large Size; Stage IIIB Melanoma
• Interventions: Biological: gp100 antigen; Biological: tyrosinase peptide; Biological: recombinant MAGE-3.1 antigen; Biological: multi-epitope melanoma peptide vaccine; Biological: incomplete Freund's adjuvant; Drug: Montanide ISA 51 VG; Drug: agatolimod sodium; Other: laboratory biomarker analysis

• Registration Number: NCT00085189
• Lead Sponsor: University of Southern California

Brief Summary

This pilot phase II trial studies how well giving vaccine therapy works in treating patients with stage IIC-IV melanoma. Vaccines made from melanoma peptides or antigens may help the body build an effective immune response to kill tumor cells

Detailed Description

PRIMARY OBJECTIVES I. To perform a two-cohort, two-stage phase II two cohort pilot trial of a multi-peptide melanoma vaccine (multi-epitope melanoma peptide vaccine) with Montanide ISA 51 (incomplete Freund's adjuvant) or ISA 51 VG (Montanide ISA 51 VG) with adjuvant 7909 (agatolimod sodium) to define the safety and tolerability of each of the regimens, and to evaluate immune reactivity to a tyrosinase/gp100/MAGE-3 class I peptide vaccine combined with Montanide ISA 51 or ISA 51 VG with CpG adjuvant 7909 in human leukocyte antigen (HLA) class I A1, A3 or A11 and B44 matched patients with surgically resected stages IIC, III and IV melanoma.

OUTLINE: Patients are assigned to 1 of 2 treatment cohorts.

COHORT I: Patients receive multi-epitope peptide melanoma peptide vaccine with incomplete Freund's adjuvant and agatolimod sodium subcutaneously (SC) at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.

COHORT II: Patients receive multi-epitope peptide melanoma peptide vaccine with Montanide ISA 51 VG and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 3 years, and then annually thereafter.

Study Timeline

• Study Start: 2004-05
• Study First Submitted: 2004-06-10
• Study First Submitted QC: 2004-06-10
• Study First Posted: 2004-06-11
• Primary Completion: 2007-09
• Study Completion: 2007-09
• Status Verified: 2014-05
• Last Update Submitted: 2014-05-20
• Last Update Posted: 2014-05-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

• Stages IIC, III and IV cutaneous, or mucosal melanoma or stages III/IV ocular melanoma that have been completely resected; those rendered disease-free by radiation or systemic chemotherapy and/or immune therapy will also be eligible; patients must be entered within 12 months of disease-free status
• Patients must be positive for at least one of human leukocyte antigen (HLA) A1, A3/A11 typed by a standard deoxyribonucleic acid (DNA)-polymerase chain reaction (PCR) assay, and HLA-B44 status must be known; patients who are B44 positive but do not express A1, A3 or A11 are not eligible for this trial
• Tumor tissue must be available for analysis of gp100 and tyrosinase expression by immunohistochemistry; positive staining for at least one antigen will be an eligibility criteria for this trial
• Serum creatinine of 2.0 mg/dl or less
• Total bilirubin of 2.0 mg/dl or less
• Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) of 2.5 X institutional norm or less
• Total white blood cell (WBC) of 3,000 or more
• At least 1500 granulocytes
• Hemoglobin of 9.0 gm/dl
• Platelet count of 100,000 per cu mm
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients will be eligible for this trial if they have failed alpha-interferon, if it is felt to be contraindicated due to a pre-existing medical or psychiatric condition or if they have refused treatment with it
• Ability to read, understand and willingness to sign an institutional review board (IRB)-approved informed consent

Exclusion Criteria

• Who are undergoing or have undergone in the past month any other therapy for their cancer, including radiation therapy and adjuvant therapy; six weeks must have elapsed for nitrosoureas
• Have major systemic infections like pneumonia or sepsis, coagulation or bleeding disorders, or other major medical illnesses of the gastrointestinal, cardiovascular or respiratory systems
• Who require steroid therapy or have been treated with steroids within 4 weeks of starting the trial
• Who are pregnant or lactating, since the risk of autoimmune reactivity to tyrosinase or gp100 is felt to present a risk to the fetus or a breast feeding infant
• Who are known to be positive for hepatitis B surface antigen (BsAg), Hepatitis C antibody or human immunodeficiency virus (HIV) antibody; since cells removed for ex vivo handling and tissue culture cannot be virus positive, and the effects of 7909 might be detrimental to HIV positive patients, patients positive for the above viruses will not be treated on this trial
• Who have had a known allergic reaction to Montanide ISA 51 or ISA 51 VG
• Who have a prior history of uveitis, autoimmune inflammatory eye disease or other autoimmune diseases other than vitiligo or controlled thyroiditis
• Who have had another malignancy within the last three years with the exception of squamous or basal carcinoma of the skin or carcinoma in situ of the cervix that have been treated with curative intent
• Who have previously received any of the peptides in the vaccine

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort I (melanoma peptide vaccine, Montanide ISA-51)	agatolimod sodium	Patients receive multi-epitope peptide melanoma peptide vaccine with incomplete Freund's adjuvant and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort I (melanoma peptide vaccine, Montanide ISA-51)	multi-epitope melanoma peptide vaccine	Patients receive multi-epitope peptide melanoma peptide vaccine with incomplete Freund's adjuvant and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort I (melanoma peptide vaccine, Montanide ISA-51)	incomplete Freund's adjuvant	Patients receive multi-epitope peptide melanoma peptide vaccine with incomplete Freund's adjuvant and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort I (melanoma peptide vaccine, Montanide ISA-51)	recombinant MAGE-3.1 antigen	Patients receive multi-epitope peptide melanoma peptide vaccine with incomplete Freund's adjuvant and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort I (melanoma peptide vaccine, Montanide ISA-51)	gp100 antigen	Patients receive multi-epitope peptide melanoma peptide vaccine with incomplete Freund's adjuvant and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort II (melanoma peptide vaccine, Montanide ISA 51 VG)	agatolimod sodium	Patients receive multi-epitope peptide melanoma peptide vaccine with Montanide ISA 51 VG and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort I (melanoma peptide vaccine, Montanide ISA-51)	tyrosinase peptide	Patients receive multi-epitope peptide melanoma peptide vaccine with incomplete Freund's adjuvant and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort II (melanoma peptide vaccine, Montanide ISA 51 VG)	laboratory biomarker analysis	Patients receive multi-epitope peptide melanoma peptide vaccine with Montanide ISA 51 VG and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort I (melanoma peptide vaccine, Montanide ISA-51)	laboratory biomarker analysis	Patients receive multi-epitope peptide melanoma peptide vaccine with incomplete Freund's adjuvant and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort II (melanoma peptide vaccine, Montanide ISA 51 VG)	tyrosinase peptide	Patients receive multi-epitope peptide melanoma peptide vaccine with Montanide ISA 51 VG and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort II (melanoma peptide vaccine, Montanide ISA 51 VG)	recombinant MAGE-3.1 antigen	Patients receive multi-epitope peptide melanoma peptide vaccine with Montanide ISA 51 VG and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort II (melanoma peptide vaccine, Montanide ISA 51 VG)	gp100 antigen	Patients receive multi-epitope peptide melanoma peptide vaccine with Montanide ISA 51 VG and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort II (melanoma peptide vaccine, Montanide ISA 51 VG)	multi-epitope melanoma peptide vaccine	Patients receive multi-epitope peptide melanoma peptide vaccine with Montanide ISA 51 VG and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Cohort II (melanoma peptide vaccine, Montanide ISA 51 VG)	Montanide ISA 51 VG	Patients receive multi-epitope peptide melanoma peptide vaccine with Montanide ISA 51 VG and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Immunologic response defined as either an enzyme-linked immunosorbent spot (ELISPOT) response or a tetramer response for at least one peptide	26 weeks

Secondary Outcome Measures

Name	Time	Method
Toxicities of the vaccine preparation graded using Common Toxicity Criteria (CTC)	Up to 3 years	Will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by CTC criteria and nadir or maximum values for the laboratory measures), time of onset (i.e. weeks from initial peptide vaccination), duration, and reversibility or outcome.
Time to relapse	Up to 3 years	Will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol - for each cohort separately. To evaluate the association between immune response and time to recurrence and overall survival, the landmark method (at 26 weeks, the time of the 2nd leukapheresis for immune assessment) will be used and Kaplan-Meier curves will be calculated and the logrank test statistic will be calculated to compare the outcome of patients with or without an immunologic response.
Overall survival	Up to 3 years	Will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol - for each cohort separately. To evaluate the association between immune response and time to recurrence and overall survival, the landmark method (at 26 weeks, the time of the 2nd leukapheresis for immune assessment) will be used and Kaplan-Meier curves will be calculated and the logrank test statistic will be calculated to compare the outcome of patients with or without an immunologic response.

Trial Locations

Locations (1)

University of Southern California; 🇺🇸 Los Angeles, California, United States