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

Primary Purpose

Recurrent Melanoma, Stage IV Melanoma

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
tyrosinase peptide
MART-1:27-35 peptide vaccine
gp100 antigen
incomplete Freund's adjuvant
sargramostim
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm I (vaccine therapy)

Arm II (vaccine therapy and lower-dose sargramostim)

Arm III (vaccine therapy and higher-dose sargramostim)

Arm Description

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

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number and severity of hematologic and non-hematologic toxicities observed using the Common Toxicity Criteria (CTC) version 2.0
Proportion of objective responses (complete response [CR] and partial response [PR]) observed

Full Information

First Posted
September 11, 2000
Last Updated
January 24, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00006243
Brief Title
Vaccine Therapy and Sargramostim in Treating Patients With Stage IV Malignant Melanoma
Official Title
Melanoma Vaccines: Differentiation Antigen Peptides (MART-1:27-35, Tyrosinase and Gp-100) as Immune Targets
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
October 2000 (undefined)
Primary Completion Date
May 2006 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief 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
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Melanoma, Stage IV Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (vaccine therapy)
Arm Type
Experimental
Arm Description
Patients receive tyrosinase peptide, MART-1:27-35 peptide vaccine, and gp100 antigen admixed in incomplete Freund's adjuvant SC on day 1 of weeks 0, 3, 6, 9, 12, and 24.
Arm Title
Arm II (vaccine therapy and lower-dose sargramostim)
Arm Type
Experimental
Arm Description
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 Title
Arm III (vaccine therapy and higher-dose sargramostim)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
tyrosinase peptide
Other Intervention Name(s)
TYRP
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
MART-1:27-35 peptide vaccine
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
gp100 antigen
Other Intervention Name(s)
gp100
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
incomplete Freund's adjuvant
Other Intervention Name(s)
IFA, ISA-51, Montanide ISA 51
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
sargramostim
Other Intervention Name(s)
GM-CSF, Leukine, Prokine
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Changes in tumor antigen peptide specific immune responses
Description
Plots of the percent changes in these factors from their pretreatment levels against time will be constructed.
Time Frame
Baseline and 24 weeks
Secondary Outcome Measure Information:
Title
Number and severity of hematologic and non-hematologic toxicities observed using the Common Toxicity Criteria (CTC) version 2.0
Time Frame
Up to 3 years
Title
Proportion of objective responses (complete response [CR] and partial response [PR]) observed
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Svetomir Markovic
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

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

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