Safety Study of Adjuvant Vaccine to Treat Melanoma Patients

Back to results

Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

NY-ESO-1 protein; Poly-ICLC; Montanide

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Melanoma, Skin Cancer, Adjuvant Therapy, Oncogenesis, LAGE, Cancer Immunity, Neoplasms, Immunogenicity, Vaccine, Immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

Histological diagnosis of malignant melanoma, stages IIB-IV in radiologically confirmed cCr without clinical evidence of disease.
At least 4 weeks since surgery prior to first dosing of study agent.
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
Patients must have an ECOG performance status of <2 (ECOG criteria published in [67].
Life expectancy > 6 months.
Age > 18 years.
Able and willing to give written informed consent for participation in the trial (see Section 12.2).

Exclusion Criteria

Serious illnesses, e.g., serious infections requiring antibiotics.
Previous bone marrow or stem cell transplant.
History of immunodeficiency disease (such as HIV) or autoimmune disease except vitiligo.
Metastatic disease to the central nervous system.
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.
Prior chemotherapy or vaccine therapy.
Radiation therapy, biological therapy or surgery within 4 weeks prior to first dose of study agent.
Concomitant treatment with systemic corticosteroids greater than physiologic doses. Topical (but not at the proposed vaccination sites) or inhalational steroids are permitted.
Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent.
Pregnancy or lactation.
Women of childbearing potential not using a medically acceptable means of contraception.
Psychiatric or addictive disorders that may compromise the ability to give informed consent.
Lack of availability of the patient for immunological and clinical follow-up assessment.
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

Sites / Locations

New York University Langone Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Dose-escalation component

Phase II is the randomized component.

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT01079741

First Posted

March 2, 2010

Last Updated

January 16, 2018

Sponsor

Nina Bhardwaj

Collaborators

Ludwig Institute for Cancer Research, Oncovir, Inc., Cancer Research Institute, New York City

1. Study Identification

Unique Protocol Identification Number

NCT01079741

Brief Title

Safety Study of Adjuvant Vaccine to Treat Melanoma Patients

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 Type

Interventional

2. Study Status

Record Verification Date

November 2017

Overall Recruitment Status

Completed

Study Start Date

September 2010 (undefined)

Primary Completion Date

March 11, 2013 (Actual)

Study Completion Date

March 11, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Nina Bhardwaj

Collaborators

Ludwig Institute for Cancer Research, Oncovir, Inc., Cancer Research Institute, New York City

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose-escalation component

Arm Type

Experimental

Arm Description

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.

Arm Title

Phase II is the randomized component.

Arm Type

Active Comparator

Arm Description

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 Type

Biological

Intervention Name(s)

NY-ESO-1 protein; Poly-ICLC; Montanide

Other Intervention Name(s)

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.

Intervention Description

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).

Primary Outcome Measure Information:

Title

Phase I, Number of Participants With SAE and DLT

Description

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 Outcome Measure Information:

Title

CD4+ and CD8+ Response

Description

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

Title

NY-ESO-1 Expression by IHC

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria Histological diagnosis of malignant melanoma, stages IIB-IV in radiologically confirmed cCr without clinical evidence of disease. At least 4 weeks since surgery prior to first dosing of study agent. Laboratory values within the following limits: Hemoglobin > 10.0 g/dL Neutrophil count > 1.5 x l09/L Lymphocyte count > Lower limit of institutional normal Platelet count > 80 x l09/L Serum creatinine < 2.0 mg/dL Serum bilirubin < 2 x upper limit of institutional normal AST/ALT < 2 x upper limit of institutional normal Patients must have an ECOG performance status of <2 (ECOG criteria published in [67]. Life expectancy > 6 months. Age > 18 years. Able and willing to give written informed consent for participation in the trial (see Section 12.2). Exclusion Criteria Serious illnesses, e.g., serious infections requiring antibiotics. Previous bone marrow or stem cell transplant. History of immunodeficiency disease (such as HIV) or autoimmune disease except vitiligo. Metastatic disease to the central nervous system. 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. Prior chemotherapy or vaccine therapy. Radiation therapy, biological therapy or surgery within 4 weeks prior to first dose of study agent. Concomitant treatment with systemic corticosteroids greater than physiologic doses. Topical (but not at the proposed vaccination sites) or inhalational steroids are permitted. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent. Pregnancy or lactation. Women of childbearing potential not using a medically acceptable means of contraception. Psychiatric or addictive disorders that may compromise the ability to give informed consent. Lack of availability of the patient for immunological and clinical follow-up assessment. 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

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

Anna Pavlick, D.O.

Organizational Affiliation

NYU Langone Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

New York University Langone Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.med.nyu.edu/clinicaltrials/

Description

Click here for more information about this study: 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

Melanoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial