NY-ESO-1 Protein Vaccine With Imiquimod in Melanoma (Adjuvant Setting)

NCT ID: NCT00142454

Last Updated: 2022-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-24
• Study Completion Date: 2006-04-25

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.

Conditions

Malignant Melanoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imiquimod + NY-ESO-1

Patients applied topical imiquimod followed by vaccination with intradermal injections of the NY-ESO-1 protein.

Group Type: EXPERIMENTAL

Imiquimod

Intervention Type: DRUG

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.

NY-ESO-1 protein

Intervention Type: BIOLOGICAL

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.

Interventions

Imiquimod

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: DRUG

NY-ESO-1 protein

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Aldara

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Research Institute, New York City

OTHER

Sponsor Role: collaborator

Ludwig Institute for Cancer Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nina Bhardwaj, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Sylvia Adams, MD

Role: STUDY_DIRECTOR

NYU Langone Health

Locations

NYU Cancer Institute

New York, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 18566444 (View on PubMed)

Other Identifiers

NYU 04-53

Identifier Type: OTHER

Identifier Source: secondary_id

LUD2004-006

Identifier Type: -

Identifier Source: org_study_id