Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety Study of Adjuvant Vaccine to Treat Melanoma Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01079741
Recruitment Status : Completed
First Posted : March 3, 2010
Results First Posted : February 13, 2018
Last Update Posted : February 13, 2018
Sponsor:
Collaborators:
Ludwig Institute for Cancer Research
Oncovir, Inc.
Cancer Research Institute, New York City
Information provided by (Responsible Party):
Nina Bhardwaj, Icahn School of Medicine at Mount Sinai

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The incidence of melanoma is increasing with an estimated incidence of 59,940 cases and an annual death rate of 8110 in 2007. Although patients diagnosed with early stage disease have an excellent clinical outcome, patients diagnosed with advanced or recurrent disease, continue to have a high mortality rate, even with initial optimal surgical resection. Effective adjuvant strategies are needed to increase the time to progression and to decrease the recurrence rate. Immunotherapy has long been recognized as a potential therapy for melanoma; the goal of adjuvant vaccine therapy is to train the endogenous immune system to recognize and target minimal residual disease.

Condition or disease Intervention/treatment Phase
Melanoma Biological: NY-ESO-1 protein; Poly-ICLC; Montanide Phase 1 Phase 2

Detailed Description:

This is a Phase I open label dose escalation study of the TLR3 agonist Poly-ICLC as an adjuvant for NY-ESO-1 protein vaccination in patients with high risk melanoma in clinical complete remission (cCr), followed by a randomized Phase II component in which patients will be randomized to subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide® ISA-51 VG (Montanide) (Arm B).

Patients with histological confirmed malignant melanoma, AJCC Stages: IIB, IIC, III or IV, who are in complete clinical remission (cCr) but at high risk of disease recurrence, will be eligible for enrollment, regardless of whether antigen expression in the autologous tumor can be demonstrated by either PCR or immunohistochemistry.

Primary Objectives:

  • Phase I: To define the safety of subcutaneous vaccination with NY-ESO-1 protein, Montanide and escalating doses of Poly-ICLC.
  • Phase II: To evaluate the induction of humoral and T cell (CD4+ and CD8+) immunity to subcutaneous vaccination with NY-ESO-1 protein in combination with Poly-ICLC when given with or without Montanide.

Exploratory analyses:

  • Evaluation of primary tumor expression of NY-ESO-1 by IHC or RT-PCR.
  • Histologic quantitation of original tumor TILs (tumor infiltrating lymphocytes), CD3+ cells, evaluation of mitotic index and correlation of this data with immunologic response.
  • Correlation of NY-ESO-1 specific T cell responses with HLA type
  • Investigation of polymorphisms for TLR3 through germline SNP analysis.
  • Clinical Outcome (Time to Progression) reported descriptively.
  • Skin section analysis of protein/adjuvant treated sites for immune cell infiltration and gene expression analysis
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/Phase II Open Label Study of the TLR3 Agonist Poly-ICLC as an Adjuvant for NY-ESO-1 Protein Vaccination With or Without Montanide ® ISA-51 VG in Patients With High Risk Melanoma in Complete Clinical Remission
Study Start Date : September 2010
Actual Primary Completion Date : March 11, 2013
Actual Study Completion Date : March 11, 2013

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Dose-escalation component
Phase I represents the dose-escalation component with Poly-ICLC given in combination with NY-ESO-1 and Montanide in an open-label fashion. The dose of Poly-ICLC will be increased stepwise from 0.35mg to 1.4mg while the dose of NY-ESO-1 antigen and Montanide will be held constant.
 Biological: NY-ESO-1 protein; Poly-ICLC; Montanide

Phase I represents the dose-escalation component with Poly-ICLC given in combination with NY-ESO-1 and Montanide in an open-label fashion. The dose of Poly-ICLC will be increased stepwise from 0.35mg to 1.4mg while the dose of NY-ESO-1 antigen (100µg) and Montanide (1.1mL) will be held constant.

Phase II: The doses of NY-ESO-1 and Montanide will remain the same as in Phase I; the highest tolerated Phase I dose of Poly-ICLC will become the Phase II Poly-ICLC dose. In Phase II, patients will be randomized to a subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide (Arm B).

Other Names:
  • Cancer-Testis (CT) antigen expression: NY-ESO-1
  • Poly ICLC: carboxymethylcellulose, polyinosinic-polycytidylic acid & poly-L-lysine double-stranded RNA
  • Montanide® ISA-51 VG: mineral oil-based adjuvant; also called (IFA)incomplete Freund's adjuvant.
Active Comparator: Phase II is the randomized component.
The doses of NY-ESO-1 and Montanide will remain the same as in Phase I; the highest tolerated Phase I dose of Poly-ICLC will become the Phase II Poly-ICLC dose. In Phase II, patients will be randomized to a subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide (Arm B).
 Biological: NY-ESO-1 protein; Poly-ICLC; Montanide

Phase I represents the dose-escalation component with Poly-ICLC given in combination with NY-ESO-1 and Montanide in an open-label fashion. The dose of Poly-ICLC will be increased stepwise from 0.35mg to 1.4mg while the dose of NY-ESO-1 antigen (100µg) and Montanide (1.1mL) will be held constant.

Phase II: The doses of NY-ESO-1 and Montanide will remain the same as in Phase I; the highest tolerated Phase I dose of Poly-ICLC will become the Phase II Poly-ICLC dose. In Phase II, patients will be randomized to a subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide (Arm B).

Other Names:
  • Cancer-Testis (CT) antigen expression: NY-ESO-1
  • Poly ICLC: carboxymethylcellulose, polyinosinic-polycytidylic acid & poly-L-lysine double-stranded RNA
  • Montanide® ISA-51 VG: mineral oil-based adjuvant; also called (IFA)incomplete Freund's adjuvant.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Phase I, Number of Participants With SAE and DLT [ Time Frame: 52 weeks ]
    Safety measured by number of Serious Adverse Events per the CTEP v4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE) and Dose Limiting Toxicity (DLT).


Secondary Outcome Measures :
  1. CD4+ and CD8+ Response [ Time Frame: Up to 52 weeks ]
    Cellular response evaluated for the induction of cellular T cell (CD4+ and CD8+) immunity to subcutaneous vaccination with NY-ESO-1 protein in combination with Poly-ICLC when given with or without Montanide. Number of participants with increase CD4+ and CD8+ levels.

  2. NY-ESO-1 Expression by IHC [ Time Frame: up to 52 weeks ]
    Analysis of immune cell infiltration at the injection site by IHC. IHC analysis of immune cell infiltration was performed for each arm using a scoring system. 0: No expression of the marker of interest, 1: single cells or small clusters (<5 cells together) expressing marker of interest, 2: medium size clusters of cells expressing marker of interest, and 3: huge and homogeneously positive clusters of cells expressing marker of interest.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Histological diagnosis of malignant melanoma, stages IIB-IV in radiologically confirmed cCr without clinical evidence of disease.
  2. At least 4 weeks since surgery prior to first dosing of study agent.

  3. Laboratory values within the following limits:

    1. Hemoglobin > 10.0 g/dL
    2. Neutrophil count > 1.5 x l09/L
    3. Lymphocyte count > Lower limit of institutional normal
    4. Platelet count > 80 x l09/L
    5. Serum creatinine < 2.0 mg/dL
    6. Serum bilirubin < 2 x upper limit of institutional normal
    7. AST/ALT < 2 x upper limit of institutional normal
  4. Patients must have an ECOG performance status of <2 (ECOG criteria published in [67].
  5. Life expectancy > 6 months.
  6. Age > 18 years.
  7. Able and willing to give written informed consent for participation in the trial (see Section 12.2).

Exclusion Criteria

  1. Serious illnesses, e.g., serious infections requiring antibiotics.
  2. Previous bone marrow or stem cell transplant.
  3. History of immunodeficiency disease (such as HIV) or autoimmune disease except vitiligo.
  4. Metastatic disease to the central nervous system.
  5. Other malignancy within 3 years prior to entry into the study, except for treated early-stage melanoma or non-melanoma skin cancer, or cervical carcinoma in situ.
  6. Prior chemotherapy or vaccine therapy.
  7. Radiation therapy, biological therapy or surgery within 4 weeks prior to first dose of study agent.
  8. Concomitant treatment with systemic corticosteroids greater than physiologic doses. Topical (but not at the proposed vaccination sites) or inhalational steroids are permitted.
  9. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent.
  10. Pregnancy or lactation.
  11. Women of childbearing potential not using a medically acceptable means of contraception.
  12. Psychiatric or addictive disorders that may compromise the ability to give informed consent.
  13. Lack of availability of the patient for immunological and clinical follow-up assessment.
  14. Children <18 years of age who cannot undergo the leukapheresis procedure, do not meet the disease staging and/or the size criteria for frequent blood donations
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01079741


Locations
Layout table for location information
United States, New York
New York University Langone Medical Center
New York, New York, United States, 10016
Sponsors and Collaborators
Nina Bhardwaj
Ludwig Institute for Cancer Research
Oncovir, Inc.
Cancer Research Institute, New York City
Investigators
Layout table for investigator information
Principal Investigator: Nina Bhardwaj, MD, PhD NYU Langone Health
Principal Investigator: Anna Pavlick, D.O. NYU Langone Health
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: Nina Bhardwaj, Director, Tumor Vaccine Program, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT01079741    
Other Study ID Numbers: GCO 13-1391
First Posted: March 3, 2010    Key Record Dates
Results First Posted: February 13, 2018
Last Update Posted: February 13, 2018
Last Verified: November 2017
Keywords provided by Nina Bhardwaj, Icahn School of Medicine at Mount Sinai:
Melanoma
Skin Cancer
Adjuvant Therapy
Oncogenesis
LAGE
 Cancer Immunity
Neoplasms
Immunogenicity
Vaccine
Immunotherapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Poly I-C
Mineral Oil
Carboxymethylcellulose Sodium
Poly ICLC
 Freund's Adjuvant
Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs
Laxatives
Gastrointestinal Agents
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic
Emollients
Dermatologic Agents