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CompletedNCT01079741Updated Feb 13, 2018Results posted

Safety Study of Adjuvant Vaccine to Treat Melanoma Patients

A Phase 1/2 interventional study of NY-ESO-1 protein; Poly-ICLC; Montanide in Melanoma, sponsored by Nina Bhardwaj. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-02-13.

Sponsored by Nina Bhardwaj · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
34
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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
02

Conditions studied

  • Melanoma

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Keywords

  • Melanoma
  • Skin Cancer
  • Adjuvant Therapy
  • Oncogenesis
  • LAGE
  • Cancer Immunity
  • Neoplasms
  • Immunogenicity
  • Vaccine
  • Immunotherapy
03

In context

Melanoma

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

This study's enrollment of 34 is below the median of 38 across 2,351 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

Nina Bhardwaj is the lead sponsor of 7 studies on the registry; none are open to participants now.

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

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
34 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • BiologicalNY-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).

    Also known as: 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.

06

What researchers measure

Primary outcomes

  1. Phase I, Number of Participants With SAE and DLT

    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).

    Time frame: 52 weeks

Secondary outcomes

  1. CD4+ and CD8+ Response

    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.

    Time frame: Up to 52 weeks

  2. NY-ESO-1 Expression by IHC

    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.

    Time frame: up to 52 weeks

07

Results

Posted Feb 13, 2018

Participant flow

Cohort 1: Dose Level 1 (Weeks 1-12)
Participant flow — Cohort 1: Dose Level 1 (Weeks 1-12)
MilestonePoly-ICLC 0.35mgPoly-ICLC 0.7mgPoly-ICLC 1.4mgNY-ESO-1 Protein and Poly-ICLCNY-ESO-1 Protein, Poly-ICLC and Montanide
Started30000
Completed30000
Not completed00000
Cohort 2: Dose Level 2 (Weeks 13-24)
Participant flow — Cohort 2: Dose Level 2 (Weeks 13-24)
MilestonePoly-ICLC 0.35mgPoly-ICLC 0.7mgPoly-ICLC 1.4mgNY-ESO-1 Protein and Poly-ICLCNY-ESO-1 Protein, Poly-ICLC and Montanide
Started04000
Completed03000
Not completed01000
Withdrew: Disease progression01000
Cohort 3: Dose Level 3 (Weeks 25-36)
Participant flow — Cohort 3: Dose Level 3 (Weeks 25-36)
MilestonePoly-ICLC 0.35mgPoly-ICLC 0.7mgPoly-ICLC 1.4mgNY-ESO-1 Protein and Poly-ICLCNY-ESO-1 Protein, Poly-ICLC and Montanide
Started00300
Completed00000
Not completed00300
Phase 2 (Weeks 37-48)
Participant flow — Phase 2 (Weeks 37-48)
MilestonePoly-ICLC 0.35mgPoly-ICLC 0.7mgPoly-ICLC 1.4mgNY-ESO-1 Protein and Poly-ICLCNY-ESO-1 Protein, Poly-ICLC and Montanide
Started0001212
Completed000129
Not completed00003
Withdrew: Withdrawal by subject00003

Outcome measures

PrimaryPhase I, Number of Participants With SAE and DLT

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).

Time frame:
52 weeks
Reported as:
Count of participants · Participants
Phase I, Number of Participants With SAE and DLT
ParticipantsPoly-ICLC 0.35 mgPoly-ICLC 0.70 mgPoly-ICLC 1.4mg
Serious Adverse Events001
DLT000
SecondaryCD4+ and CD8+ Response

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.

Time frame:
Up to 52 weeks
Reported as:
Count of participants · Participants
CD4+ and CD8+ Response
ParticipantsNY-ESO-1 Protein and Poly-ICLCNY-ESO-1 Protein, Poly-ICLC and Montanide
CD4 Responder109
CD8 Responder14
SecondaryNY-ESO-1 Expression by IHC

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.

Time frame:
up to 52 weeks
Reported as:
Mean · units on a scale
NY-ESO-1 Expression by IHC
units on a scaleNY-ESO-1 Protein and Poly-ICLCNY-ESO-1 Protein, Poly-ICLC and Montanide
CD3 lymphocytes1.500 ± 0.7071.944 ± 0.682
CD4 lymphocytes1.318 ± 0.6432.167 ± 0.661
CD8 lymphocytes1.091 ± 0.4371.222 ± 0.565
CD20 B cells0.773 ± 0.5181.500 ± 0.500
CD11c dendritic cells1.455 ± 0.6112.111 ± 0.741

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Poly-ICLC 0.35 mg0/3 (0%)0/3 (0%)3/3 (100%)
Poly-ICLC 0.70 mg0/4 (0%)0/4 (0%)4/4 (100%)
Poly-ICLC 1.4mg0/3 (0%)1/3 (33.3%)3/3 (100%)
Phase 2, Arm 10/12 (0%)0/12 (0%)12/12 (100%)
Phase 2, Arm 20/12 (0%)0/12 (0%)12/12 (100%)
Most frequent serious events
Most frequent serious events
EventPoly-ICLC 0.35 mgPoly-ICLC 0.70 mgPoly-ICLC 1.4mgPhase 2, Arm 1Phase 2, Arm 2
Stent placementCardiac disorders0/30/41/30/120/12
Most frequent other events
Showing 10 of 76
Most frequent other events
EventPoly-ICLC 0.35 mgPoly-ICLC 0.70 mgPoly-ICLC 1.4mgPhase 2, Arm 1Phase 2, Arm 2
Influenza like illnessGeneral disorders3/32/41/39/128/12
Injection site erythemaGeneral disorders3/33/42/312/129/12
Injection site noduleGeneral disorders3/33/43/36/1212/12
Injection site edemaGeneral disorders3/31/40/30/120/12
Injection site painGeneral disorders3/33/43/312/1212/12
Injection site indurationGeneral disorders1/33/43/30/120/12
Injection site urticariaGeneral disorders0/32/43/30/120/12
MyalgiaMusculoskeletal and connective tissue disorders3/32/41/34/126/12
FatigueGeneral disorders2/33/41/310/128/12
Injection site discomfortGeneral disorders1/33/42/38/124/12

Baseline characteristics

Age, Continuous
Age, Continuous(years)Poly-ICLC 0.35 mgPoly-ICLC 0.70 mgPoly-ICLC 1.4mgNY-ESO-1 Protein and Poly-ICLCNY-ESO-1 Protein, Poly-ICLC and MontanideTotal
Median64 (42 to 72)65 (39 to 74)73 (64 to 78)50 (21 to 69)57 (24 to 83)55 (21 to 74)
Sex: Female, Male
Sex: Female, Male(Participants)Poly-ICLC 0.35 mgPoly-ICLC 0.70 mgPoly-ICLC 1.4mgNY-ESO-1 Protein and Poly-ICLCNY-ESO-1 Protein, Poly-ICLC and MontanideTotal
Female0205613
Male3237621
Pathologic Staging
Pathologic Staging(Participants)Poly-ICLC 0.35 mgPoly-ICLC 0.70 mgPoly-ICLC 1.4mgNY-ESO-1 Protein and Poly-ICLCNY-ESO-1 Protein, Poly-ICLC and MontanideTotal
IIA000101
IIB001102
IIC100012
IIIA100023
IIIB110439
IIIC0324413
IV000224
08

Study locations

1 site
  • New York University Langone Medical Center
    New York, New York 10016, United States
09

References and documents

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 13, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01079741
Lead sponsor
Nina Bhardwaj
Collaborators
Ludwig Institute for Cancer Research, Oncovir, Inc., Cancer Research Institute, New York City
Responsible party
Nina Bhardwaj (Director, Tumor Vaccine Program, Icahn School of Medicine at Mount Sinai) — Sponsor-investigator
First posted
Mar 3, 2010
Start date
Sep 2010
Primary completion
Mar 11, 2013
Completion
Mar 11, 2013
Results posted
Feb 13, 2018
Last update
Feb 13, 2018

Study contacts

Nina Bhardwaj, MD, PhD
principal investigator · NYU Langone Health
Anna Pavlick, D.O.
principal investigator · NYU Langone Health

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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