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Safety Study of Adjuvant Vaccine to Treat Melanoma Patients

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2014 by Mount Sinai School of Medicine
Sponsor:
Collaborators:
Ludwig Institute for Cancer Research
Oncovir, Inc.
Cancer Research Institute, New York City
Information provided by (Responsible Party):
Nina Bhardwaj, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01079741
First received: March 2, 2010
Last updated: October 27, 2014
Last verified: October 2014

March 2, 2010
October 27, 2014
November 2014
October 2015   (final data collection date for primary outcome measure)
Phase I, to define the safety of subcutaneous vaccination with NY-ESO-1 protein, Montanide and escalating doses of Poly-ICLC [ Time Frame: Disease status is assessed at baseline, wks 4 & 12 and after 4th vaccination (wks 14 & 22). At wk 52, disease status is assessed through patient follow-up with study physicians or through contact with the patient's regular treating physician. ] [ Designated as safety issue: Yes ]
Up to 3 cohorts of 3 patients will be given a subcutaneous vaccination of 100µg NY-ESO-1 protein emulsified in 1.1mL Montanide® ISA-51VG (day 1) with escalating doses of Poly-ICLC. Dose-escalation will continue if no DLTs are observed in the 3 patients in a given cohort.
Same as current
Complete list of historical versions of study NCT01079741 on ClinicalTrials.gov Archive Site
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. [ Time Frame: Disease status is assessed at baseline, wks 4 & 12 and after 4th vaccination (wks 14 & 22). At wk 52, disease status is assessed through patient follow-up with study physicians or through contact with the patient's regular treating physician. ] [ Designated as safety issue: No ]
When Phase I is complete (no cohort 3 DLT observed) 24 new patients are randomized in Phase II to receive treatment under Arm A or Arm B. They receive s.c. vaccinations of 100μg NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A); or with 100μg NY-ESO-1 protein, Poly-ICLC dose TBD and 1.1mL Montanide (Arm B). Administrations occur every 3 wks on study wks 1,4,7,&10. Injections may occur w/in +/-3 days of planned date. Blood samples are obtained at baseline, 1 wk after vaccinations, and 1&3 months after last vaccination for assessment of NY-ESO-1 specific antibodies and CD4+ & CD8+ T cells.
Same as current
Not Provided
Not Provided
 
Safety Study of Adjuvant Vaccine to Treat Melanoma Patients
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

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.

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
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Melanoma
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: carboxymethlycellulose, polyinosinic-polycytidylic acid & poly-L-lysine double-stranded RNA
  • Montanide® ISA-51 VG: mineral oil-based adjuvant; also called (IFA)incomplete Freund's adjuvant.
  • 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.
    Intervention: Biological: NY-ESO-1 protein; Poly-ICLC; Montanide
  • 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).
    Intervention: Biological: NY-ESO-1 protein; Poly-ICLC; Montanide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
33
October 2015
October 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Juliet Escalon, RN, CCN,CCRC, ANP 212-263-4401 juliet.escalon@nyumc.org
Contact: Anna Pavlick, D.O. 212-731-5431 anna.pavlick@nyumc.org
United States
 
NCT01079741
GCO 13-1391
Yes
Nina Bhardwaj, Mount Sinai School of Medicine
Nina Bhardwaj
  • Ludwig Institute for Cancer Research
  • Oncovir, Inc.
  • Cancer Research Institute, New York City
Principal Investigator: Nina Bhardwaj, MD, PhD New York University Langone Medical Center
Principal Investigator: Anna Pavlick, D.O. New York University Langone Medical Center
Mount Sinai School of Medicine
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP