Back to resultsNY-ESO-1 Protein Vaccine With Imiquimod in Melanoma (Adjuvant Setting)
Primary Purpose
Malignant Melanoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Imiquimod
NY-ESO-1 protein
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Melanoma focused on measuring Malignant melanoma, Stages IIB-III
Eligibility Criteria
Inclusion Criteria: Had histologically confirmed, resected American Joint Committee on Cancer Stage IIB, IIC or III malignant melanoma Fully recovered from surgery Age ≥ 18 years; children were excluded from this study, as the safety of imiquimod had not been established in patients below the age of 18 Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Adequate organ and marrow function as defined below: absolute neutrophil count: ≥ 1500/μL hemoglobin: ≥ 9 g/dL platelets: ≥ 100,000/μL total bilirubin: ≤ 1.5 × institutional upper limit of normal (ULN) aspartate aminotransferase/alanine aminotransferase (AST/ALT): ≤ 2.5 × institutional ULN creatinine: ≤ 1.5 × institutional ULN Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Received chemotherapy, immunotherapy (including interferon), or radiotherapy within 4 weeks prior to first dosing of study agent Prior treatment with NY-ESO-1 vaccines Known human immunodeficiency virus infection or autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus), as these conditions could have interfered with the evaluation of the induced immune response; patients with vitiligo or melanoma-associated hypopigmentation were not excluded History of allergic reactions attributed to compounds of similar chemical or biologic composition to imiquimod or other agents used in the study Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection,symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would have limited compliance with study requirements Pregnancy or lactation Women of childbearing potential not using a medically acceptable means of contraception Known history of inflammatory skin disorders, as imiquimod might have exacerbated these conditions Chronic corticosteroid or immunosuppressive therapies, as these might have interfered with the evaluation of the induced immune response Lack of availability for immunological and clinical follow-up assessments
Sites / Locations
- NYU Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Imiquimod + NY-ESO-1
Arm Description
Patients applied topical imiquimod followed by vaccination with intradermal injections of the NY-ESO-1 protein.
Outcomes
Primary Outcome Measures
Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (fatal). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, and any other medically indicated assessments, including patient interviews, from the time informed consent was signed through the last follow-up visit. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Secondary Outcome Measures
Number of Patients With Cellular Antibody Response to NY-ESO-1 at Two or More Post-vaccination Time Points
Assays to assess cluster of differentiation (CD)8+ and CD4+ antigen-specific responses were performed at baseline (Cycle 1 Day 1), throughout the vaccination period (Day 1 of Cycles 2 through 4 and Day 10 of each cycle), and at the 2 post-treatment follow-up visits (Weeks 13 and 16) by enzyme-linked immune absorbent spot (ELISPOT) assay following prior in vitro sensitization. A 3-fold increase in spot-forming cells over baseline defined a positive response. Suitable antigens may have included recombinant viral vectors encoding NY-ESO-1, or NY-ESO-1 overlapping peptides, depending upon availability.
Number of Patients With Humoral Antibody Response to NY-ESO-1
Assays to assess NY-ESO-1 specific antibodies were performed at baseline (Cycle 1 Day 1), throughout the vaccination period (Day 1 of Cycles 2 through 4 and Day 10 of each cycle), and at the 2 post-treatment follow-up visits (Weeks 13 and 16) by enzyme-linked immunosorbent assay (ELISA). Samples were diluted serially. The induction and augmentation of immunity were defined as an increase in antibody titer of ≥ 3× over buffer alone or ≥ 4× the pre-vaccination titer, respectively. Sera from the responding patients were tested a second time against a pool of NY-ESO-1 overlapping peptides to confirm NY-ESO-1 specificity; the number of patients in the table reflect the patients with confirmed NY-ESO-1 specificity.
Full Information
NCT ID
NCT00142454
First Posted
September 1, 2005
Last Updated
October 3, 2022
Sponsor
Ludwig Institute for Cancer Research
Collaborators
Cancer Research Institute (CRI)
1. Study Identification
Unique Protocol Identification Number
NCT00142454
Brief Title
NY-ESO-1 Protein Vaccine With Imiquimod in Melanoma (Adjuvant Setting)
Official Title
NY-ESO-1 Protein Vaccination in Malignant Melanoma Administered With Imiquimod as Adjuvant
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
August 24, 2005 (Actual)
Primary Completion Date
April 25, 2006 (Actual)
Study Completion Date
April 25, 2006 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ludwig Institute for Cancer Research
Collaborators
Cancer Research Institute (CRI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This was a Phase 1, single-arm, open-label, pilot study of NY-ESO-1 protein vaccination with imiquimod as an adjuvant in patients with resected Stage IIB, IIC, and III malignant melanoma. The primary study objective was to determine the safety of NY-ESO-1 protein/imiquimod treatment, and the secondary objective was to evaluate the immunogenicity of treatment.
Detailed Description
Patients applied imiquimod (250 mg) topically to a designated area of healthy skin on the upper inner arm or inner thigh (the cream remained on the skin overnight for 6-10 hours) every day for 5 consecutive days (i.e., for the first 5 days of Cycles 1-3 and for the first 4 days of Cycle 4). The NY-ESO-1 protein (100 μg) was injected intradermally into the imiquimod-pretreated area on Day 3 of each cycle for 4 consecutive 21-day cycles.
Safety was monitored continuously. Immunization was assessed by the generation of NY-ESO-1-specific cluster of differentiation (CD)4+ and CD8+ T cell responses in enzyme-linked immunosorbent spot (ELISPOT) assays and by the development or augmentation of NY-ESO-1-specific antibody titers, assessed by enzyme-linked immunosorbent assay (ELISA).
Blood samples were obtained for the assessment of clinical biochemistry and hematology, and physical examinations were performed at baseline, on Day 1 of each cycle, and at a follow-up visit at Week 13.
Skin biopsies of the vaccinated area were obtained 48 hours after the last injection (Day 5 of Cycle 4). To avoid irritation, imiquimod was not applied after the biopsies.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Melanoma
Keywords
Malignant melanoma, Stages IIB-III
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Imiquimod + NY-ESO-1
Arm Type
Experimental
Arm Description
Patients applied topical imiquimod followed by vaccination with intradermal injections of the NY-ESO-1 protein.
Intervention Type
Drug
Intervention Name(s)
Imiquimod
Other Intervention Name(s)
Aldara
Intervention Description
Patients applied imiquimod cream at bedtime every day for 5 consecutive days (for the first 5 days of Cycles 1-3 and for the first 4 days of Cycle 4) at a dose of 250 mg as supplied in single-use packets to a 4 x 5 cm area of healthy skin, alternating among the extremities (upper inner arms and inner thighs) in each cycle. The cream was to be rubbed into the skin until it was no longer visible. Patients were encouraged to wash their hands before and after applying cream. The application site was not occluded. The next morning, 6 to 10 hours after initial application, the treated area was washed with mild soap and water to remove any residual cream.
Intervention Type
Biological
Intervention Name(s)
NY-ESO-1 protein
Intervention Description
NY-ESO-1 protein was injected intradermally by a study physician or nurse at a dose of 100 μg into the imiquimod-pretreated area on Day 3 of each cycle for 4 consecutive 21-day cycles.
Primary Outcome Measure Information:
Title
Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Description
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (fatal). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, and any other medically indicated assessments, including patient interviews, from the time informed consent was signed through the last follow-up visit. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Time Frame
Up to 4 months
Secondary Outcome Measure Information:
Title
Number of Patients With Cellular Antibody Response to NY-ESO-1 at Two or More Post-vaccination Time Points
Description
Assays to assess cluster of differentiation (CD)8+ and CD4+ antigen-specific responses were performed at baseline (Cycle 1 Day 1), throughout the vaccination period (Day 1 of Cycles 2 through 4 and Day 10 of each cycle), and at the 2 post-treatment follow-up visits (Weeks 13 and 16) by enzyme-linked immune absorbent spot (ELISPOT) assay following prior in vitro sensitization. A 3-fold increase in spot-forming cells over baseline defined a positive response. Suitable antigens may have included recombinant viral vectors encoding NY-ESO-1, or NY-ESO-1 overlapping peptides, depending upon availability.
Time Frame
Up to 4 months
Title
Number of Patients With Humoral Antibody Response to NY-ESO-1
Description
Assays to assess NY-ESO-1 specific antibodies were performed at baseline (Cycle 1 Day 1), throughout the vaccination period (Day 1 of Cycles 2 through 4 and Day 10 of each cycle), and at the 2 post-treatment follow-up visits (Weeks 13 and 16) by enzyme-linked immunosorbent assay (ELISA). Samples were diluted serially. The induction and augmentation of immunity were defined as an increase in antibody titer of ≥ 3× over buffer alone or ≥ 4× the pre-vaccination titer, respectively. Sera from the responding patients were tested a second time against a pool of NY-ESO-1 overlapping peptides to confirm NY-ESO-1 specificity; the number of patients in the table reflect the patients with confirmed NY-ESO-1 specificity.
Time Frame
Up to 4 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Had histologically confirmed, resected American Joint Committee on Cancer Stage IIB, IIC or III malignant melanoma
Fully recovered from surgery
Age ≥ 18 years; children were excluded from this study, as the safety of imiquimod had not been established in patients below the age of 18
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Adequate organ and marrow function as defined below:
absolute neutrophil count: ≥ 1500/μL
hemoglobin: ≥ 9 g/dL
platelets: ≥ 100,000/μL
total bilirubin: ≤ 1.5 × institutional upper limit of normal (ULN)
aspartate aminotransferase/alanine aminotransferase (AST/ALT): ≤ 2.5 × institutional ULN
creatinine: ≤ 1.5 × institutional ULN
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
Received chemotherapy, immunotherapy (including interferon), or radiotherapy within 4 weeks prior to first dosing of study agent
Prior treatment with NY-ESO-1 vaccines
Known human immunodeficiency virus infection or autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus), as these conditions could have interfered with the evaluation of the induced immune response; patients with vitiligo or melanoma-associated hypopigmentation were not excluded
History of allergic reactions attributed to compounds of similar chemical or biologic composition to imiquimod or other agents used in the study
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection,symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would have limited compliance with study requirements
Pregnancy or lactation
Women of childbearing potential not using a medically acceptable means of contraception
Known history of inflammatory skin disorders, as imiquimod might have exacerbated these conditions
Chronic corticosteroid or immunosuppressive therapies, as these might have interfered with the evaluation of the induced immune response
Lack of availability for immunological and clinical follow-up assessments
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nina Bhardwaj, MD, PhD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sylvia Adams, MD
Organizational Affiliation
NYU Langone Health
Official's Role
Study Director
Facility Information:
Facility Name
NYU Cancer Institute
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
18566444
Citation
Adams S, O'Neill DW, Nonaka D, Hardin E, Chiriboga L, Siu K, Cruz CM, Angiulli A, Angiulli F, Ritter E, Holman RM, Shapiro RL, Berman RS, Berner N, Shao Y, Manches O, Pan L, Venhaus RR, Hoffman EW, Jungbluth A, Gnjatic S, Old L, Pavlick AC, Bhardwaj N. Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant. J Immunol. 2008 Jul 1;181(1):776-84. doi: 10.4049/jimmunol.181.1.776.
Results Reference
result
Learn more about this trial
NY-ESO-1 Protein Vaccine With Imiquimod in Melanoma (Adjuvant Setting)
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