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

Melanoma Clinical Trial

— Mel55  

Official title:

T Cell Activation and Immune Cell Function in Melanoma Patients Treated With recMAGE-A3 + AS15 Immunological Adjuvant System

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01425749
• Other study ID #: 15398
• Status: Active, not recruiting
• Phase: Phase 0
• First received: July 19, 2011
• Last updated: September 19, 2013
• Start date: June 2011
• Est. completion date: December 2013

Study information

• Verified date: September 2013
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 27
• Est. completion date: December 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

• Ability and willingness to give informed consent.

• Laboratory parameters as follows:

1. ANC > 1000/mm3, and Platelets > 75,000/mm3 and Hgb > 9 g/dL

2. Hepatic:

AST and ALT up to 2.5 x upper limits of normal (ULN) Bilirubin up to 2.5 x ULN Alkaline phosphatase up to 2.5 x ULN LDH up to 2x ULN

3. Renal:

Creatinine up to 1.5 x ULN

4. Serology:

HIV negative (antibody screening), Hepatitis C negative

5. HGBA1C level of < 7.5%

• Patients must be 18 years or older at study entry

Exclusion Criteria:

• Patients with primary ocular melanoma.

• Patients who have had brain metastases unless they meet the criteria outlined in the inclusion criteria

• 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:

1. Agents with putative immunomodulating activity, but with the exception of non-steroidal anti-inflammatory agents and topical steroids.

2. 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.

3. Allergy desensitization injections.

4. 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.

5. Any growth factors (e.g. GM-CSF, G-CSF, erythropoietin).

6. Interferon therapy.

7. Interleukin-2 or other interleukins.

8. Targeted therapies designed to inhibit BRAF, MAPKinase, mTOR, or their signaling pathways.

• Prior active immunotherapy or vaccines for melanoma may be an exclusion criterion in some circumstances. Exceptions to this exclusion criterion are as follows:

1. 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.

2. Patients may not have been previously administered the synthetic MAGE-A3 protein, though prior vaccinations with up to 4 synthetic MAGE-A3 peptides (up to 16 amino acids in length, each) is allowed.

• Pregnancy or the possibility of becoming pregnant during vaccine administration. Female patients of child-bearing potential must have a negative pregnancy test (urinary or serum beta-HCG) prior to administration of the first MAGE-A3 ASCI dose. Males and females must agree, in the consent form, to use effective birth control methods during the course of vaccination. Women must also not be breast feeding. This is consistent with existing standards of practice for vaccine and chemotherapy protocols.

• Patients in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol, in the opinion of the investigator.

• Patients classified according to the New York Heart Association classification as having Class III or IV heart disease.

• Patients with a body weight < 110 lbs because of the amount and frequency with which blood will be drawn, and because of the biopsies required.

• Patients must not have had prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement. Patients with an active autoimmune disorder requiring these therapies are also excluded. The following will not be exclusionary:

• Laboratory evidence of autoimmune disease (e.g. positive ANA titer) without symptoms

• Clinical evidence of vitiligo

• Other forms of depigmenting illness

• Mild arthritis requiring NSAID medications

Study Design

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

Related Conditions & MeSH terms

• Melanoma

Intervention

Biological:
• recMAGE-A3 + AS15 ASCI
Injections 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.

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Craig L Slingluff, Jr	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and severity of adverse events as a measure of safety and tolerability		Over 6 months	Yes
Primary	Enumeration of CD4 and CD8 T cell responses to MAGE-A3 epitopes and to other tumor antigens (epitope spreading) in the injection site-draining lymph node (sentinel immunized node, SIN) as a measure of immunogenicity.		After 3 doses of study drug	No
Secondary	Enumeration of CD4+ and CD8+ T cells reactive to MAGE-A3 epitopes in peripheral blood as a measure of immunogenicity.		Over 6 months	No
Secondary	Identification of antibody responses to MAGE-A3 after MAGE-A3 ASCI administration as a measure of immunogenicity.		Over 6 months	No
Secondary	Characterization of the maturation and activation of dendritic cell (DC) populations in the sentinel immunized node (SIN) after treatment with MAGE-A3 ASCI. This characterization will also be correlated with the ID/SC MAGE-A3 ASCI administration site.		Over 6 months	No
Secondary	Identification of the frequency of myeloid derived suppressor cells (MDSC) and myeloid suppressor cells in the SIN after treatment with MAGE-A3 ASCI. This characterization will also be correlated with the ID/SC MAGE-A3 ASCI administration site.		Over 6 months	No
Secondary	Identification of the functional polarity of CD4 T cells (Th1, Th2, Th17, T reg) reactive to MAGE-A3 epitopes in the peripheral blood and SIN after MAGE-A3 ASCI, administered either by IM or ID/SC injections.		Over 6 months	No
Secondary	Determination of whether CD8 T cells reactive to MAGE-A3 epitopes in the peripheral blood and SIN express perforin or granzyme B.		Over 6 months	No
Secondary	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	No
Secondary	Identification of whether MAGE-A3 ASCI induces toll-like receptor activation at the immunization site (ID/SC injection group only) and in the draining node (SIN), for all patients.		Over 6 months	No
Secondary	Analysis of gene expression profiles of tumor metastases biopsied before and after anti-MAGE-A3 immunization		Over 6 months	No
Secondary	A preliminary investigation as to whether MAGE-A3 reactive CD8+ T cells infiltrate metastatic melanoma deposits after MAGE-A3 ASCI		Over 6 months	No