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

NCT02320305 | Completed Early Phase 1 DMC

• 3 other identifiers: MC1177NCI-2014-02479P30CA015083
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 24 months

Secondary Outcomes (1)

• Adverse event rate, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Up to 24 months

Other Outcomes (1)

• 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

  Up to 24 months

Study Arms (2)

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

EXPERIMENTAL

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.

Biological: MART-1 Antigen; Drug: TLR4 Agonist GLA-SE; Other: Laboratory Biomarker Analysis

Arm II (MART-1 antigen)

EXPERIMENTAL

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.

Biological: MART-1 Antigen; Other: Laboratory Biomarker Analysis

Interventions

MART-1 Antigen BIOLOGICAL

Given IM

Also known as: Antigen LB39-AA, Antigen SK29-AA, MART-1 Tumor Antigen

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

TLR4 Agonist GLA-SE DRUG

Given IM

Also known as: GLA-SE, Glucopyranosyl Lipid A in Stable Emulsion, Glucopyranosyl Lipid Adjuvant-Stable Emulsion, Toll-like Receptor 4 Agonist GLA-SE

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

Laboratory Biomarker Analysis OTHER

Correlative studies

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• 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.

  PMID: 33955240 DERIVED

• 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.

  PMID: 32752904 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

MART-1 Antigen; glucopyranosyl lipid-A

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Melanoma-Specific Antigens; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antigens, Neoplasm; Antigens; Biological Factors

Study Officials

• Matthew Block

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2014
• First Posted: December 19, 2014
• Study Start: January 27, 2015
• Primary Completion: December 7, 2015
• Study Completion: April 11, 2019
• Last Updated: January 14, 2020

Record last verified: 2019-02

Locations

US (1)