Vaccine Therapy and Sargramostim in Treating Patients With Stage IV Malignant Melanoma

Stage IV Melanoma Clinical Trial

Official title:

Melanoma Vaccines: Differentiation Antigen Peptides (MART-1:27-35, Tyrosinase and Gp-100) as Immune Targets

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006243
• Other study ID #: NCI-2012-02359
• Secondary ID: MC9973CDR0000068
• Status: Completed
• Phase: N/A
• First received: September 11, 2000
• Last updated: January 24, 2013
• Start date: October 2000

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This randomized pilot clinical trial studies vaccine therapy and sargramostim in treating patients with stage IV malignant melanoma. Vaccines made from melanoma peptides or antigens may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as sargramostim, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving vaccine therapy together with sargramostim may be an effective treatment for malignant melanoma

Description:

PRIMARY OBJECTIVES:

I. Determine the immunological effects of immunization protocols utilizing MART-1:27-35 (MART-1:27-35 peptide vaccine), tyrosinase (tyrosinase peptide) or gp-100 (gp100 antigen) peptides suspended in incomplete Freund's adjuvant (IFA) in the presence of two different concentrations of sargramostim (GM-CSF).

II. Define the safety and toxicity profile of an immunization protocol utilizing varying concentrations of MART-1:27-35, tyrosinase and gp-100 peptides suspended in IFA in the presence of two different concentrations of GM-CSF.

III. Collect preliminary data on therapeutic efficacy as it relates to parameters of immune function in patients with stage IV malignant melanoma.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive tyrosinase peptide, MART-1:27-35 peptide vaccine, and gp100 antigen admixed in incomplete Freund's adjuvant subcutaneously (SC) on day 1 of weeks 0, 3, 6, 9, 12, and 24.

ARM II: Patients receive tyrosinase peptide, MART-1:27-35 peptide vaccine, and gp100 antigen admixed in incomplete Freund's adjuvant SC and lower-dose sargramostim SC on day 1 of weeks 0, 3, 6, 9, 12, and 24.

ARM III: Patients receive tyrosinase peptide, MART-1:27-35 peptide vaccine, and gp100 antigen admixed in incomplete Freund's adjuvant SC and higher-dose sargramostim SC on day 1 of weeks 0, 3, 6, 9, 12, and 24.

In all arms, treatment may repeat every 3 months for up to 18 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. primary completion date: May 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Human leukocyte antigen (HLA)-A2 positive

• Histologic proof of stage IV malignant melanoma with measurable disease

• Absolute neutrophil count (ANC) >= 1500

• Platelets (PLT) >= 100,000

• Alkaline phosphatase (Alk phos) =< 3 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST) =< 3 x ULN

• Creatinine (Creat) =< 1.5 x ULN

• Hemoglobin (Hgb) > 9.0

• Ability to provide informed consent

• Willingness to return to a Mayo Clinic institution for follow-up

• Life expectancy >= 12 weeks

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

• Uncontrolled or current infection

• Prior immunization with differentiation antigen peptides

• Known standard therapy for the patient's disease that is potentially curative or proven capable of extending life expectancy

• Any of the following prior therapies:

• Chemotherapy =< 4 weeks

• Mitomycin C/nitrosoureas =< 6 weeks

• Immunotherapy =<4 weeks

• Biologic therapy =< 4 weeks

• Radiation therapy =< 4 weeks

• Radiation to > 25% of bone marrow

• Failure to fully recover from effects of prior chemotherapy regardless of interval since last treatment

• New York Heart Association classification III or IV

• Seizure disorder

• Any of the following:

• Pregnant women

• Nursing women

• Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)

• Other concurrent chemotherapy, immunotherapy, or radiotherapy

• Active psychiatric disorder requiring medications (anti-psychotics)

• Known central nervous system metastases or carcinomatous meningitis

• History of other malignancy in last 5 years with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection only (it is impossible to predict the effect of study treatment on other, potentially dormant malignant diseases)

• Known immune deficiency (patients with known immune deficiencies will likely not be able to mount an immune response to the study vaccine)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Recurrent Melanoma
• Stage IV Melanoma

Intervention

Biological:
• tyrosinase peptide
Given SC
• MART-1:27-35 peptide vaccine
Given SC
• gp100 antigen
Given SC
• incomplete Freund's adjuvant
Given SC
• sargramostim
Given SC

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in tumor antigen peptide specific immune responses	Plots of the percent changes in these factors from their pretreatment levels against time will be constructed.	Baseline and 24 weeks	No
Secondary	Number and severity of hematologic and non-hematologic toxicities observed using the Common Toxicity Criteria (CTC) version 2.0		Up to 3 years	Yes
Secondary	Proportion of objective responses (complete response [CR] and partial response [PR]) observed		Up to 3 years	No