Vaccine Therapy in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

Sponsor

Ahmad Tarhini (Other)

Overall Status

Completed

CT.gov ID

NCT00471471

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy together with GM-CSF, CpG 7909, and incomplete Freund's adjuvant may make a stronger immune response and kill more tumor cells.

PURPOSE: This clinical trial is studying the side effects and how well vaccine therapy works in treating patients with recurrent stage III or stage IV melanoma that cannot be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Intraocular Melanoma Malignant Conjunctival Neoplasm Melanoma (Skin)	Biological: Peptide vaccine Biological: GM-CSF Biological: PF3512676	Phase 1

Detailed Description

OBJECTIVES:

Determine the safety of a peptide vaccine comprising MART-1:27-35 peptide, gp100:209-217 (210M) peptide, and tyrosinase peptide with sargramostim (GM-CSF) and CpG 7909 emulsified in incomplete Freund's adjuvant in patients with unresectable recurrent stage III or IV melanoma.
Determine the efficacy of immunoadjuvants CpG 7909 and GM-CSF, in terms of a strong antigen-specific CD8+ T-cell response, in these patients.
Determine the anti-pigmentary response to this regimen in these patients.
Determine the anti-tumor response, in terms of objective tumor regression, progression-free survival, and overall survival, in patients treated with this regimen.

OUTLINE: This is a pilot study.

Patients receive peptide vaccine comprising MART-1:27-35 peptide, gp100:209-217 (210M) peptide, and tyrosinase peptide with sargramostim (GM-CSF) and CpG 7909 emulsified in incomplete Freund's adjuvant subcutaneously on days 1 and 15. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline, day 50-53, and day 91-94. Samples are examined by ELISPOT assay to measure lymphocyte immune response and by flow cytometry for biomarker quantification and T-cell response.

After completion of study treatment, patients are followed up periodically for at least 2 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Safety and Immunogenicity of Vaccination With Multi-Epitope Peptide Vaccine Containing MART-1, gp100, and Tyrosinase Peptides Given With the Combination of GMCSF and CpG Oligonucleotide (CpG 7909) in ISA-Oil Adjuvant for Patients With Recurrent Inoperable Stage III or Stage IV Melanoma

Study Start Date :

Oct 1, 2008

Actual Primary Completion Date :

Dec 1, 2011

Actual Study Completion Date :

Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Peptide Vaccine + GM-CSF + Pfizer 3512676 in-ISA Oil The water-in-oil emulsion will consist of peptide (100 mcg/0.1 mL), GM-CSF (80 mcg/0.16 mL using lyophilized 500 mcg/vial reconstituted with 1 mL of sterile water), Pfizer PF3512676 (0.6 mg/0.04 mL using 15mg/mL vial) and 0.20 mLl of sterile saline. Vaccination will be given subcutaneously rotating truncal sites in the vicinity of the four nodal drainage groups of the four extremities, on days 1 and 15 of each cycle (1 cycle = 28 days) for a maximum of 13 cycles (1 year).	Biological: Peptide vaccine Multi-epitope peptide vaccine containing MART-1 (26-35, 27L), gp100 (209-217, 210M) and tyrosinase (368-376, 370D) peptides Biological: GM-CSF 80 mcg/0.16 mL using lyophilized 500 mcg/vial reconstituted with 1 mL of sterile water given subcutaneously rotating truncal sites in the vicinity of the four nodal drainage groups of the four extremities, on days 1 and 15 of each cycle (1 cycle = 28 days) for a maximum of 13 cycles (1 year). Other Names: Sargramostim Biological: PF3512676 0.6 mg/0.04 mL given subcutaneously rotating truncal sites in the vicinity of the four nodal drainage groups of the four extremities, on days 1 and 15 of each cycle (1 cycle = 28 days) for a maximum of 13 cycles (1 year). Other Names: CpG 7909 agatolimod

Arm

Intervention/Treatment

Experimental: Peptide Vaccine + GM-CSF + Pfizer 3512676 in-ISA Oil

The water-in-oil emulsion will consist of peptide (100 mcg/0.1 mL), GM-CSF (80 mcg/0.16 mL using lyophilized 500 mcg/vial reconstituted with 1 mL of sterile water), Pfizer PF3512676 (0.6 mg/0.04 mL using 15mg/mL vial) and 0.20 mLl of sterile saline. Vaccination will be given subcutaneously rotating truncal sites in the vicinity of the four nodal drainage groups of the four extremities, on days 1 and 15 of each cycle (1 cycle = 28 days) for a maximum of 13 cycles (1 year).

Biological: Peptide vaccine

Multi-epitope peptide vaccine containing MART-1 (26-35, 27L), gp100 (209-217, 210M) and tyrosinase (368-376, 370D) peptides

Biological: GM-CSF

80 mcg/0.16 mL using lyophilized 500 mcg/vial reconstituted with 1 mL of sterile water given subcutaneously rotating truncal sites in the vicinity of the four nodal drainage groups of the four extremities, on days 1 and 15 of each cycle (1 cycle = 28 days) for a maximum of 13 cycles (1 year).

Other Names:

Sargramostim

Biological: PF3512676

0.6 mg/0.04 mL given subcutaneously rotating truncal sites in the vicinity of the four nodal drainage groups of the four extremities, on days 1 and 15 of each cycle (1 cycle = 28 days) for a maximum of 13 cycles (1 year).

Other Names:

CpG 7909

agatolimod

Outcome Measures

Primary Outcome Measures

Safety [up to 1 year]
Number of grade 2 or greater allergic reactions (including generalized urticaria) or any grade 3 or greater adverse event

Secondary Outcome Measures

Immunologic response [up to 94 days]
Change in the circulating effector T-cells.
Objective tumor regression [2 months]
Change in tumor size will be performed at the end of cycle 2.
Depigmentation evaluation [up to 2 years]
Change in cutaneous depigmentation using careful inspection of the skin of the torso by a Wood's lamp.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed melanoma meeting the following criteria:
Unresectable recurrent disease
Stage III or IV disease
Cutaneous, ocular, or mucosal melanoma
Measurable disease as defined by the RECIST criteria
HLA-A2 positive
Prior brain metastases allowed provided adequate surgical or radiologic treatment for brain disease

PATIENT CHARACTERISTICS:

ECOG performance status 0 or 1
WBC ≥ 3,000/mm³
Lymphocytes ≥ 1,000/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 1.5 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
AST and ALT ≤ 2.5 times ULN
Lactic dehydrogenase ≤ 2.0 times ULN
aPTT < 40 seconds
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception for ≥ 1 week before, during, and for ≥ 2 weeks after completion of study therapy
No conditions of immunosuppression
Negative titers for antinuclear antibody (≤ 1/80) and antidouble stranded DNA (≤ 1/10)
No serious illnesses including, but not limited to, any of the following:
Bleeding disorders
Autoimmune diseases
Severe obstructive or restrictive pulmonary diseases
Active systemic infections
Inflammatory bowel disorders
No serious cardiovascular disease including, but not limited to, any of the following:
Uncontrolled congestive heart failure
Hypertension
Cardiac ischemia
Myocardial infarction,
Severe cardiac arrhythmia
HIV1 and 2 negative
HTLV-1 negative
Hepatitis B and C negative
No significant psychiatric disease, medical intervention, or other condition that, in the opinion of the principal investigator, would limit study compliance
No active infection within the past week, including unexplained fever (temperature > 38.1°C)

PRIOR CONCURRENT THERAPY:

Fully recovered from prior major surgery
More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas), hormonal therapy, radiotherapy, or biological therapy
More than 1 week since prior antibiotics
More than 28 days since prior investigational agent
No prior vaccination with MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) peptides alone or in combination
Patients with history of vaccination with peptides other than MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) peptides allowed
More than 4 weeks since prior and no concurrent systemic immunosuppressive therapy, including steroids
Patients on maintenance steroids given at physiologic doses because of adrenal insufficiency are eligible
More than 2 weeks since prior and no concurrent treatment with systemic steroids, including oral steroids, continuous use of topical steroid creams or ointments, or any inhaled steroids
No concurrent anticoagulants, except to keep an indwelling line patent
No other concurrent anticancer therapy, including chemotherapy, immunotherapy, radiotherapy, experimental programs, and/or surgery