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MART-1 Antigen With or Without TLR4 Agonist GLA-SE in Treating Patients With Stage II-IV Melanoma That Has Been Removed by Surgery

Primary Purpose

Stage IIA Skin Melanoma, Stage IIB Skin Melanoma, Stage IIC Skin Melanoma

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
MART-1 Antigen
TLR4 Agonist GLA-SE
Laboratory Biomarker Analysis
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage IIA Skin Melanoma

Eligibility Criteria

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

Inclusion Criteria:

  • Central pathology review submission; Note: this review for MART-1 positivity is mandatory prior to randomization to confirm eligibility
  • Human leukocyte antigen (HLA)-A2-positive
  • Histologic proof of stage II, III or IV melanoma that has been completely resected or completely treated with ablative therapy (ex: stereotactic body radiosurgery, radiofrequency ablation, cryoablation) with no current evidence of disease, as demonstrated by imaging within 2 months (stage III or stage IV; must be computed tomography [CT], magnetic resonance imaging [MRI], or positron emission tomography [PET]/CT) or 6 months (stage II; may be chest x-ray, CT, MRI, or PET/CT)
  • Absolute neutrophil count (ANC) >= 1500 mL
  • Hemoglobin (Hgb) > 10 g/dL
  • Platelets (PLT) >= 50,000 mL
  • Aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)
  • Alkaline phosphatase =< 3 x ULN
  • Ability to provide informed consent
  • Willingness to return to Mayo Clinic Rochester for follow-up
  • Life expectancy >= 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • For women of childbearing potential, a negative serum pregnancy test =< 7 days prior to registration
  • Willingness to provide mandatory blood samples for correlative research

Exclusion Criteria:

  • Uncontrolled or current infection
  • Known standard therapy for the patient's disease that is potentially curative or proven capable of extending life expectancy
  • Known allergy to any of the vaccine or adjuvant components, including eggs

  • Any of the following prior therapies with interval since most recent treatment:

    • Chemotherapy =< 4 weeks prior to registration
    • Biologic or immunologic therapy =< 4 weeks prior to registration
    • Radiation therapy =< 4 weeks prior to registration
  • Failure to fully recover from side effects of prior therapy or surgery

  • 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.)
  • Known immune deficiency, including human immunodeficiency virus (HIV) infection
  • History of systemic autoimmune disease, as patients with ongoing autoimmunity may be at an increased risk of autoimmune toxicity from the study vaccine
  • Current or recent (=< 4 weeks) use of immunosuppressive medications including systemic (inhaled, oral, or intravenous [IV]) corticosteroids; Note: use of corticosteroids in doses not exceeding those used for adrenal replacement is acceptable
  • History of brain metastases; EXCEPTION: patients with a solitary brain metastasis that has been completely resected, and who have no ongoing central nervous system (CNS) symptoms and an MRI documenting no evidence of CNS disease at least 3 months after resection and within 30 days of registration, are eligible for treatment
  • Other active malignancy =< 5 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy > 5 years prior to registration, the patient must not be receiving other cancer treatment

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I (MART-1 antigen and TLR4 antagonist GLA-SE)

Arm II (MART-1 antigen)

Arm Description

Patients receive MART-1 antigen and TLR4 antagonist GLA-SE IM on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients receive MART-1 antigen IM on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Immune response
A patient is considered to have achieved an immune response if there is a 2-fold or more increase from pre-treatment levels in the absolute number of vaccine peptide-specific (MART-1a-specific) CTL as measured by tetramer staining, or if the frequency of MART-1a-specific CTL is initially undetectable (< 0.05% of CD8 T cells) and becomes detectable during the vaccine treatment period. The proportion of successes will be estimated and the exact binomial 95% confidence intervals for the true immune response rate will be calculated.

Secondary Outcome Measures

Adverse event rate, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

Full Information

First Posted
December 15, 2014
Last Updated
January 13, 2020
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02320305
Brief Title
MART-1 Antigen With or Without TLR4 Agonist GLA-SE in Treating Patients With Stage II-IV Melanoma That Has Been Removed by Surgery
Official Title
Peptide Vaccine With Glucopyranosyl Lipid A - Stable Oil-in-Water Emulsion (GLA-SE) for Patients With Resected Melanoma: A Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
January 27, 2015 (Actual)
Primary Completion Date
December 7, 2015 (Actual)
Study Completion Date
April 11, 2019 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized pilot clinical trial studies melanoma antigen recognized by T-cells 1 (MART-1) antigen with or without toll-like receptor 4 (TLR4) agonist glucopyranosyl lipid A-stable oil-in-water emulsion (GLA-SE) in treating patients with stage II-IV melanoma that has been removed by surgery. Vaccines made from MART-1a peptide or antigen may help the body build an effective immune response to kill tumor cells. Giving TLR4 agonist GLA-SE with MART-1 antigen may help increase the immune response to MART-1a antigen.
Detailed Description
PRIMARY OBJECTIVES: I. Evaluate the immune response of each immunization regimen to determine an optimal regimen in terms of immune response to recommend for phase II testing. SECONDARY OBJECTIVES: I. Evaluate the adverse events profile of each immunization regimen. TERTIARY OBJECTIVES: I. Describe the immunological efficacy of the vaccine preparations as measured by the frequency and interferon (IFN) gamma production of peptide-specific cytotoxic T lymphocytes (CTL). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive MART-1 antigen and TLR4 antagonist GLA-SE intramuscularly (IM) on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive MART-1 antigen IM on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, stage II patients are followed up at 10 weeks and then at 6, 12, 18, and 24 months and stage III-IV patients are followed up at 3, 6, 9, 12, 15, 18, 21, and 24 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage IIA Skin Melanoma, Stage IIB Skin Melanoma, Stage IIC Skin Melanoma, Stage IIIA Skin Melanoma, Stage IIIB Skin Melanoma, Stage IIIC Skin Melanoma, Stage IV Skin Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (MART-1 antigen and TLR4 antagonist GLA-SE)
Arm Type
Experimental
Arm Description
Patients receive MART-1 antigen and TLR4 antagonist GLA-SE IM on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm II (MART-1 antigen)
Arm Type
Experimental
Arm Description
Patients receive MART-1 antigen IM on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
MART-1 Antigen
Other Intervention Name(s)
Antigen LB39-AA, Antigen SK29-AA, MART-1 Tumor Antigen
Intervention Description
Given IM
Intervention Type
Drug
Intervention Name(s)
TLR4 Agonist GLA-SE
Other Intervention Name(s)
GLA-SE, Glucopyranosyl Lipid A in Stable Emulsion, Glucopyranosyl Lipid Adjuvant-Stable Emulsion, Toll-like Receptor 4 Agonist GLA-SE
Intervention Description
Given IM
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Immune response
Description
A patient is considered to have achieved an immune response if there is a 2-fold or more increase from pre-treatment levels in the absolute number of vaccine peptide-specific (MART-1a-specific) CTL as measured by tetramer staining, or if the frequency of MART-1a-specific CTL is initially undetectable (< 0.05% of CD8 T cells) and becomes detectable during the vaccine treatment period. The proportion of successes will be estimated and the exact binomial 95% confidence intervals for the true immune response rate will be calculated.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Adverse event rate, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Description
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
Time Frame
Up to 24 months
Other Pre-specified Outcome Measures:
Title
Immunological efficacy of the vaccine preparations against tumor antigen MART-1a will be described as a function of the vaccine immune adjuvant, as measured by the frequency and IFN gamma production of vaccine-peptide specific CTL
Description
Additional markers of immune activation will be described as a function of each vaccine preparation. Each factor will be plotted against time. Each graph will be visually inspected for trends across time. The number of patients with at least a 2-fold change in the number of cells/plasma concentration or with a level that goes from undetectable to detectable after the 1st course will be determined. The marker profile of those who derived an immune response and those who did not will be tabled to visually compare and contrast the pattern of marker-specific responses between these patient groups.
Time Frame
Up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Central pathology review submission; Note: this review for MART-1 positivity is mandatory prior to randomization to confirm eligibility Human leukocyte antigen (HLA)-A2-positive Histologic proof of stage II, III or IV melanoma that has been completely resected or completely treated with ablative therapy (ex: stereotactic body radiosurgery, radiofrequency ablation, cryoablation) with no current evidence of disease, as demonstrated by imaging within 2 months (stage III or stage IV; must be computed tomography [CT], magnetic resonance imaging [MRI], or positron emission tomography [PET]/CT) or 6 months (stage II; may be chest x-ray, CT, MRI, or PET/CT) Absolute neutrophil count (ANC) >= 1500 mL Hemoglobin (Hgb) > 10 g/dL Platelets (PLT) >= 50,000 mL Aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) Alkaline phosphatase =< 3 x ULN Ability to provide informed consent Willingness to return to Mayo Clinic Rochester for follow-up Life expectancy >= 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 For women of childbearing potential, a negative serum pregnancy test =< 7 days prior to registration Willingness to provide mandatory blood samples for correlative research Exclusion Criteria: Uncontrolled or current infection Known standard therapy for the patient's disease that is potentially curative or proven capable of extending life expectancy Known allergy to any of the vaccine or adjuvant components, including eggs Any of the following prior therapies with interval since most recent treatment: Chemotherapy =< 4 weeks prior to registration Biologic or immunologic therapy =< 4 weeks prior to registration Radiation therapy =< 4 weeks prior to registration Failure to fully recover from side effects of prior therapy or surgery 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.) Known immune deficiency, including human immunodeficiency virus (HIV) infection History of systemic autoimmune disease, as patients with ongoing autoimmunity may be at an increased risk of autoimmune toxicity from the study vaccine Current or recent (=< 4 weeks) use of immunosuppressive medications including systemic (inhaled, oral, or intravenous [IV]) corticosteroids; Note: use of corticosteroids in doses not exceeding those used for adrenal replacement is acceptable History of brain metastases; EXCEPTION: patients with a solitary brain metastasis that has been completely resected, and who have no ongoing central nervous system (CNS) symptoms and an MRI documenting no evidence of CNS disease at least 3 months after resection and within 30 days of registration, are eligible for treatment Other active malignancy =< 5 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy > 5 years prior to registration, the patient must not be receiving other cancer treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Block
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

Citations:
PubMed Identifier
33955240
Citation
Kobayashi RH, Mandujano JF, Rehman SM, Kobayashi AL, Geng B, Atkinson TP, Melamed I, Turpel-Kantor E, Clodi E, Gupta S. Treatment of children with primary immunodeficiencies with a subcutaneous immunoglobulin 16.5% (cutaquig(R) [octanorm]). Immunotherapy. 2021 Jul;13(10):813-824. doi: 10.2217/imt-2021-0064. Epub 2021 May 6.
Results Reference
derived
PubMed Identifier
32752904
Citation
Grewal EP, Erskine CL, Nevala WK, Allred JB, Strand CA, Kottschade LA, McWilliams RR, Dronca RS, Yakovich AJ, Markovic SN, Block MS. Peptide vaccine with glucopyranosyl lipid A-stable oil-in-water emulsion for patients with resected melanoma. Immunotherapy. 2020 Sep;12(13):983-995. doi: 10.2217/imt-2020-0085. Epub 2020 Aug 5.
Results Reference
derived

Learn more about this trial

MART-1 Antigen With or Without TLR4 Agonist GLA-SE in Treating Patients With Stage II-IV Melanoma That Has Been Removed by Surgery

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