CompletedNCT00705640Mel48Updated Dec 16, 2016

Vaccine Therapy in Treating Patients With Advanced Melanoma

A Phase 1 interventional study of incomplete Freund's adjuvant and multi-epitope melanoma peptide vaccine in Intraocular Melanoma, Malignant Conjunctival Neoplasm and Melanoma (Skin), sponsored by Craig L Slingluff, Jr. Completed at 1 site in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2016-12-16.

Sponsored by Craig L Slingluff, Jr · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 45
Allocation: Randomized
Ages: 18 Years to 120 Years
Sex: All

Study summary

RATIONALE: Vaccine therapy may help the body build an effective immune response to kill tumor cells.

PURPOSE: This randomized clinical trial is studying how well vaccine therapy works in treating patients with advanced melanoma.

Read the detailed description

OBJECTIVES:

To assess the circulating CD8 T-cell response to vaccination with a multipeptide vaccine in patients with advanced melanoma.
To determine whether immunization with peptides and incomplete Freund's adjuvant induces lymph-node-like aggregates (LNLA) and tertiary lymphoid organs (TLOs) in the skin of these patients.
To determine whether extended immunization (vaccinations 4-6) is associated with induction of negative immune-regulatory processes in the vaccination site microenvironment/TLO.
To characterize peptide-reactive CD4 and CD8 T cells in loco at sites of immunization with a multipeptide vaccine.
To characterize the expression of toll-like receptors 4, 7, 8, and 9, and MyD88 in dendritic cells infiltrating vaccination sites over the course of 6 vaccinations and after vaccination.

OUTLINE: Patients are randomized to 1 of 10 arms.

All patients receive primary vaccine comprising melanoma multipeptides and tetanus toxoid helper peptide emulsified in incomplete Freund's adjuvant, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Vaccines are administered in a single skin location on an extremity clinically uninvolved with melanoma. A replicate vaccine site is identified for each patient for skin biopsy with or with out replica vaccine administration.

Arm 1A: Patients receive no replicate vaccine. Patients undergo surgical biopsy at replicate vaccine site on day 1.
Arm 1B: Patients receive replicate vaccine comprising incomplete Freund's adjuvant only SC and ID on day 1 and undergo surgical biopsy at replicate vaccine site on day 8 (1 week after replicate vaccine 1).
Arm 1C: Patients receive replicate vaccine comprising incomplete Freund's adjuvant only SC and ID on days 1, 8, and 15 and undergo surgical biopsy at replicate vaccine site on day 22 (1 week after replicate vaccine 3).
Arm 1D: Patients receive replicate vaccine comprising incomplete Freund's adjuvant only SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on day 50 (1 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after biopsy.
Arm 1E: Patients receive replicate vaccine comprising incomplete Freund's adjuvant only SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on day 85 (6 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after biopsy.
Arm 2A: Patients receive no replicate vaccine. Patients undergo surgical biopsy at replicate vaccine site on day 1.
Arm 2B: Patients receive replicate vaccine (the same as primary vaccine) SC and ID on day 1 and undergo surgical biopsy at replicate vaccine site on day 8 (1 week after replicate vaccine 1).
Arm 2C: Patients receive replicate vaccine (the same as primary vaccine) SC and ID on days 1, 8, and 15 and undergo surgical biopsy at replicate vaccine site on day 22 (1 week after replicate vaccine 3).
Arm 2D: Patients receive replicate vaccine (the same as primary vaccine) SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on day 50 (1 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after biopsy.
Arm 2E: Patients receive replicate vaccine (the same as primary vaccine) SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on day 85 (1 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after biopsy.

Tissue biopsies are examined by reverse transcriptase-PCR, IHC, protein analysis, flow cytometry, and western blot. Blood samples are collected periodically and examined by ELIspot assay, tetramer staining, and proliferation assay.

After completion of study therapy, patients are followed annually.

Conditions studied

Intraocular Melanoma
Malignant Conjunctival Neoplasm
Melanoma (Skin)

Browse trials for

Melanoma 3,006

Keywords

stage II melanoma
stage III melanoma
stage IV melanoma
ciliary body and choroid melanoma, medium/large size
ciliary body and choroid melanoma, small size
conjunctival melanoma
extraocular extension melanoma
iris melanoma
metastatic intraocular melanoma
recurrent intraocular melanoma

In context

Melanoma

3,006 studies on the registry are indexed under Melanoma; 520 are open to participants now.

This study's enrollment of 45 is above the median of 38 across 2,351 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

Craig L Slingluff, Jr is the lead sponsor of 24 studies on the registry; 1 is open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 2 (40%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 120 Years
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed melanoma that meets one of the following criteria:
- Stage IIB-IV melanoma rendered clinically free of disease by surgery, other therapy, or spontaneous remission within the past 6 months
- Stage III or IV melanoma with disease
Persistent or metastatic disease allowed if RECIST criteria for measurable disease is not met
Multiple primary melanomas allowed
Prior or concurrent metastasis from a cutaneous, mucosal, ocular, or unknown primary site allowed
No clinically detectable melanoma deemed likely by the investigator to require intervention during the first 12 weeks of the study that would require premature discontinuation (e.g., untreated bone metastases at risk for fracture or rapidly progressive low-volume disease)
Brain metastases allowed if all of the following criteria are met:
- The total number of brain metastases ever is ≤ 3
- The brain metastases have been completely removed by surgery or have been treated completely by stereotactic radiotherapy
- There has been no evident growth of any brain metastasis since treatment
- No treated brain metastasis > 2 cm in diameter
At least two intact axillary and/or inguinal lymph node basins
Prior lymph node biopsy allowed if lymphoscintigraphy demonstrates intact drainage to a node in that basin
- If a sentinal lymph node is not located by lymphoscintigraphy, patient is not eligible for study
HLA-A1, -A2, -A3, or -A11 positive
Either eligible for, but refused interferon therapy OR not a candidate for interferon therapy for the following reasons:
- Active ischemic heart disease or cerebrovascular disease
- Anginal syndrome requiring ongoing medications or history of myocardial infarction or arrhythmia disorder
- History of treatment for depression, active depression, or other psychiatric disorder
- Autoimmune disorders
- Hypersensitivity to interferon-alfa or any component associated with interferon therapy
- Debilitating medical conditions such as severe pulmonary disease or severe diabetes mellitus
- Thyroid abnormalities, where thyroid function cannot be maintained in the normal range without medication
- Resected stage IV melanoma
- Discontinued interferon therapy due to the occurrence of a major toxicity that has been documented by the treating physician
- Experienced tumor progression while on interferon or after completing interferon therapy
- Missed the standard-of-care enrollment window for interferon therapy initiation

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
ANC > 1,000/mm\^3
Platelets > 100,000/mm\^3
Hemoglobin > 9 g/dL
AST and ALT ≤ 2.5 times upper limit of normal (ULN)
Bilirubin ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
Creatinine ≤ 1.5 times ULN
Hepatitis C and HIV negative (antibody screening)
Hemoglobin_A1C level \< 7%
Body weight ≥ 110 pounds
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during study treatment
No New York Heart Association class III-IV heart disease
No known or suspected allergies to any component of the vaccine
No medical contraindication or potential problem in complying with the requirements of the protocol

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Prior peptide vaccines (including MELITAC 12.1 and similar vaccines) or non-peptide vaccines allowed
At least 1 week since prior stereotactic radiotherapy, such as gamma knife
No influenza vaccine ≥ 2 weeks before, during, and ≥ 2 weeks after completion of study therapy
More than 4 weeks since prior and no concurrent use of any of the following:
- Systemic cytotoxic chemotherapy (6 weeks for nitrosoureas)
- Radiotherapy
- Other experimental therapy
- Agents with putative immunomodulating activity (with the exception of non-steroidal anti-inflammatory agents and topical steroids)
- Allergy desensitization injections
- Systemic corticosteroids, administered parenterally or orally
- Inhaled steroids (e.g., fluticasone propionate [Advair® or Flovent®] or triamcinolone acetonide [Azmacort®])
  - Topical corticosteroids and steroids with very low solubility administered nasally for local effects only allowed (e.g., mometasone furoate [Nasonex®])
- Growth factors (e.g., sargramostim [GM-CSF], filgrastim [G-CSF], or epoetin alfa)
- Interferon therapy
- Aldesleukin or other interleukins
- Street drugs
At least 1 month since prior and no other concurrent investigational drugs or therapy
At least 12 weeks since prior melanoma vaccine for patients who have recurred or progressed either after or during treatment with vaccine

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 45 participants (actual)

Study arms

Experimental
Arm 1A
Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive no replicate vaccine. Patients undergo surgical biopsy at replicate vaccine site on day 1.
Biological: incomplete Freund's adjuvant · Biological: multi-epitope melanoma peptide vaccine · Biological: tetanus toxoid helper peptide · Procedure: biopsy
Experimental
Arm 1B
Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine comprising incomplete Freund's adjuvant only SC and ID on day 1 and undergo surgical biopsy at replicate vaccine site on day 8 (1 week after replicate vaccine 1).
Biological: incomplete Freund's adjuvant · Biological: multi-epitope melanoma peptide vaccine · Biological: tetanus toxoid helper peptide · Procedure: biopsy
Experimental
Arm 1C
Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine comprising incomplete Freund's adjuvant only SC and ID on days 1, 8, and 15 and undergo surgical biopsy at replicate vaccine site on day 22 (1 week after replicate vaccine 3).
Biological: incomplete Freund's adjuvant · Biological: multi-epitope melanoma peptide vaccine · Biological: tetanus toxoid helper peptide · Procedure: biopsy
Experimental
Arm 1D
Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine comprising incomplete Freund's adjuvant only SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on day 50 (1 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after biopsy.
Biological: incomplete Freund's adjuvant · Biological: multi-epitope melanoma peptide vaccine · Biological: tetanus toxoid helper peptide · Procedure: biopsy
Experimental
Arm 1E
Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine comprising incomplete Freund's adjuvant only SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on day 85 (6 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after biopsy.
Biological: incomplete Freund's adjuvant · Biological: multi-epitope melanoma peptide vaccine · Biological: tetanus toxoid helper peptide · Procedure: biopsy
Experimental
Arm 2A
Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive no replicate vaccine. Patients undergo surgical biopsy at replicate vaccine site on day 1.
Biological: incomplete Freund's adjuvant · Biological: multi-epitope melanoma peptide vaccine · Biological: tetanus toxoid helper peptide · Procedure: biopsy
Experimental
Arm 2B
Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine (the same as primary vaccine) SC and ID on day 1 and undergo surgical biopsy at replicate vaccine site on day 8 (1 week after replicate vaccine 1).
Biological: incomplete Freund's adjuvant · Biological: multi-epitope melanoma peptide vaccine · Biological: tetanus toxoid helper peptide · Procedure: biopsy
Experimental
Arm 2C
Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine (the same as primary vaccine) SC and ID on days 1, 8, and 15 and undergo surgical biopsy at replicate vaccine site on day 22 (1 week after replicate vaccine 3).
Biological: incomplete Freund's adjuvant · Biological: multi-epitope melanoma peptide vaccine · Biological: tetanus toxoid helper peptide · Procedure: biopsy
Experimental
Arm 2D
Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine (the same as primary vaccine) SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on day 50 (1 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after biopsy.
Biological: incomplete Freund's adjuvant · Biological: multi-epitope melanoma peptide vaccine · Biological: tetanus toxoid helper peptide · Procedure: biopsy
Experimental
Arm 2E
Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine (the same as primary vaccine) SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on day 85 (1 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after biopsy.
Biological: incomplete Freund's adjuvant · Biological: multi-epitope melanoma peptide vaccine · Biological: tetanus toxoid helper peptide · Procedure: biopsy

Interventions

Biologicalincomplete Freund's adjuvant
Given subcutaneously and intradermally
Biologicalmulti-epitope melanoma peptide vaccine
Given subcutaneously and intradermally
Biologicaltetanus toxoid helper peptide
Given subcutaneously and intradermally
Procedurebiopsy
Patients undergo surgical biopsy at replicate vaccine site

What researchers measure

Primary outcomes

Features of lymphoid neogenesis at the replicate immunization site
Time frame: Up to Day 85

Study locations

1 site

University of Virginia Cancer Center
Charlottesville, Virginia 22908, United States

References and documents

Publications

Pollack KE, Meneveau MO, Melssen MM, Lynch KT, Koeppel AF, Young SJ, Turner S, Kumar P, Sol-Church K, Mauldin IS, Slingluff CL Jr. Incomplete Freund's adjuvant reduces arginase and enhances Th1 dominance, TLR signaling and CD40 ligand expression in the vaccine site microenvironment. J Immunother Cancer. 2020 Apr;8(1):e000544. doi: 10.1136/jitc-2020-000544. PubMed 32350119 ↗
Judge JM, Chianese-Bullock KA, Schroen AT, Slingluff CL Jr. Usefulness of prestudy assessment of patient willingness to undergo tissue biopsy for correlative studies in a melanoma vaccine trial. Clin Trials. 2013 Feb;10(1):143-50. doi: 10.1177/1740774512464438. Epub 2012 Nov 29. PubMed 23197414 ↗
Schaefer JT, Patterson JW, Deacon DH, Smolkin ME, Petroni GR, Jackson EM, Slingluff CL Jr. Dynamic changes in cellular infiltrates with repeated cutaneous vaccination: a histologic and immunophenotypic analysis. J Transl Med. 2010 Aug 20;8:79. doi: 10.1186/1479-5876-8-79. PubMed 20727190 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 16, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00705640
Lead sponsor: Craig L Slingluff, Jr
Collaborators: National Cancer Institute (NCI)
Responsible party: Craig L Slingluff, Jr (Professor of Surgery; Director, Human Immune Therapy Center, University of Virginia) — Sponsor-investigator
First posted: Jun 26, 2008
Start date: May 2008
Primary completion: Jun 2009
Last update: Dec 16, 2016

Study contacts

Craig L. Slingluff, MD

principal investigator · University of Virginia

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Dec 2016. You cannot join it, but the record below documents what was studied.

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