Study to Assess Safety and Immune Response of Stage IIB-IV Resected Melanoma After Treatment With MAGE-A3 ASCI

NCT01425749 | Completed Early Phase 1 Results DMC

• 1 other identifier: CSlingluff
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The goals of this study are to 1) assess the safety of recombinant MAGE-A3 protein combined with AS15 Immunological Adjuvant System (recMAGE-A3 + AS15) as an Antigen-Specific Cancer Immunotherapeutic (MAGE-A3 ASCI) when administered in two different administration sites, intramuscular (IM) or intradermal/subcutaneous (ID/SC), and 2) to provide preliminary data on the immunological response to ASCI in the injection site microenvironment, in the node draining the vaccine site (sentinel immunized node) and in the blood and whether there are large differences in the magnitude, persistence, or type of immune response induced as a function of the ASCI injection. Evaluation of immune responses to the ASCI will include, amonth others antiMAGE-A3 antibody responses and CD4+ and CD8+ T cell responses.

Conditions

Melanoma

Keywords

melanoma; MAGE-A3; immunotherapy; adjuvant; skin cancer; skin diseases; immunology

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-related Adverse Events as a Measure of Safety and Tolerability

  grade 2 treatment-related adverse events graded by CTCAE v4

  Over 6 months

• Enumeration of CD4 and CD8 T Cell Responses to MAGE-A3 Epitopes in the Injection Site-draining Lymph Node (Sentinel Immunized Node, SIN) as a Measure of Immunogenicity.

  Flow cytometry on in vitro stimulated lymphocytes. A positive immune response was identified as one with bifunctional CD4+ or CD8+ T cells, producing both TNF alpha and IFN-gamma after exposure to antigen.

  One week after 3 doses of study drug, on day 22.

Secondary Outcomes (4)

• Enumeration of CD4+ and CD8+ T Cells Reactive to MAGE-A3 Epitopes in Peripheral Blood as a Measure of Immunogenicity.

  Over 6 months

• Identification of Antibody Responses to MAGE-A3 After MAGE-A3 ASCI Administration as a Measure of Immunogenicity.

  Over 6 months, typically weeks 1, 7, 13, 26

• Characterization of the Maturation and Activation of Dendritic Cell (DC) Populations in the Sentinel Immunized Node (SIN) After Treatment With MAGE-A3 ASCI.

  Over 3 weeks

• A Preliminary Evaluation of Cellular Components of the Injection Site Microenvironment for Cutaneous Immunization With MAGE-A3 ASCI (Activated T Cells, Th1,Th2, Th17 Infiltrating CD4 Cells, Regulatory T Cells, and Myeloid-derived Suppressor Cells).

  Over 6 months

Study Arms (2)

Arm A

EXPERIMENTAL

Intramuscular injections of recMAGE-A3 + AS15 ASCI.

Biological: recMAGE-A3 + AS15 ASCI

Arm B

EXPERIMENTAL

Intradermal/Subcutaneous injections of recMAGE-A3 + AS15 ASCI. Requires an injection site biopsy at Day 8 and Day 50.

Biological: recMAGE-A3 + AS15 ASCI

Interventions

recMAGE-A3 + AS15 ASCI BIOLOGICAL

Injections of recMAGE-A3 + AS15 ASCI will be given 5 times at 3-week intervals. This will either be administered cutaneously or intramuscularly depending on the study group. The injected doses will be administered in alternating extremities at each visit.

Also known as: recMAGE-A3 + AS15 ASCI IM, recMAGE-A3 + AS15 ASCI ID/SC

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically proven melanoma that meets one of the following two criteria:
• Stage IIB-IV melanoma rendered clinically free of disease by surgery, other therapy, or spontaneous remission within 6 months prior to registration.
• Stage III or IV melanoma with disease. Patients may be eligible if there are definite or equivocal findings of persistent or metastatic disease as long as those findings do not meet RECIST criteria for measurable disease.
• Expression of MAGE-A3 by the tumor (primary or metastasis).
• Patients may have had multiple primary melanomas.
• Patients may have had, or may have, a metastasis from a cutaneous, mucosal, unknown primary site.
• Patients with brain metastases may be eligible if all of the following are true:
• The total number of brain metastases ever is less than or equal to 3.
• The brain metastases have been completely removed by surgery or have been treated completely by stereotactic radiotherapy. Stereotactic radiotherapy, such as gamma knife, can be used up to 1 week prior to study entry.
• There has been no evident growth of any brain metastasis since treatment.
• No treated brain metastasis is greater than 2 cm in diameter at the time of protocol entry.
• Patients must have at least two intact axillary and/or inguinal lymph node basins.
• The interferon education packet must be completed satisfactorily for those who are eligible for, but refuse, interferon therapy.
• All patients must have:
• ECOG performance status of 0 or 1.

You may not qualify if:

• Patients with primary ocular melanoma.
• Patients who are currently receiving systemic cytotoxic chemotherapy, radiation, monoclonal antibody therapy, or other experimental therapy, or who have received this therapy within the preceding 4 weeks. Patients who are currently receiving nitrosoureas or who have received this therapy within the preceding 6 weeks.
• Patients who have received isolated limb infusion (ILI) or isolated limb perfusion (ILP) for melanoma will not be eligible unless they have experienced tumor progression after the ILI/ILP, and the ILI/ILP was not performed within the prior 12 weeks.
• Patients will not be eligible if there is clinically detectable melanoma deemed likely by the investigator to require intervention during the first 12 weeks of the study that would require premature discontinuation.
• Patients with known or suspected allergies to any component of the MAGE-A3 ASCI.
• Patients receiving the following medications at study entry or within the preceding 4 weeks are excluded, except as specified below:
• Agents with putative immunomodulating activity, but with the exception of non-steroidal anti-inflammatory agents and topical steroids.
• Antibodies to CTLA-4, PD-1, PD-L1, or CD137 may not have been received in the past 12 weeks, and patients will be eligible only if there has been melanoma progression since that therapy was administered.
• Allergy desensitization injections.
• Systemic corticosteroids, administered parenterally or orally. Inhaled steroids are not permitted. Topical corticosteroids are acceptable, including steroids with very low solubility administered nasally for local effects only.
• Any growth factors (e.g. GM-CSF, G-CSF, erythropoietin).
• Interferon therapy.
• Interleukin-2 or other interleukins.
• Targeted therapies designed to inhibit BRAF, MAPKinase, mTOR, or their signaling pathways.
• Patients who have recurred or progressed either after or during administration of a melanoma vaccine may be eligible to enroll in this study 12 weeks following their last vaccination.

Sponsors & Collaborators

• Craig L Slingluff, Jr: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• Slingluff CL Jr, Petroni GR, Olson WC, Smolkin ME, Chianese-Bullock KA, Mauldin IS, Smith KT, Deacon DH, Varhegyi NE, Donnelly SB, Reed CM, Scott K, Galeassi NV, Grosh WW. A randomized pilot trial testing the safety and immunologic effects of a MAGE-A3 protein plus AS15 immunostimulant administered into muscle or into dermal/subcutaneous sites. Cancer Immunol Immunother. 2016 Jan;65(1):25-36. doi: 10.1007/s00262-015-1770-9. Epub 2015 Nov 18.

  PMID: 26581199 RESULT

MeSH Terms

Conditions

Melanoma; Skin Neoplasms; Skin Diseases

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Craig L Slingluff Jr
• Organization: University of Virginia

cls8h@virginia.edu

434-924-1730

Study Officials

• Craig L Slingluff, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery; Director, Human Immune Therapy Center

Study Record Dates

• First Submitted: July 19, 2011
• First Posted: August 30, 2011
• Study Start: June 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: October 1, 2015
• Last Updated: April 4, 2016
• Results First Posted: April 4, 2016

Record last verified: 2016-03

Locations

US (1)