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Dendritic Cells (DC) Vaccine for Metastatic Melanoma

Primary Purpose

Metastatic Melanoma

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Vaccination

About this trial

This is an interventional treatment trial for Metastatic Melanoma focused on measuring Melanoma

Eligibility Criteria

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

Inclusion Criteria:

Subjects must have Stage III-IV melanoma (any tumor thickness and any number of lymph node involvement, and in-transit metastases, or distant metastases) (AJCC). Each diagnosis will be confirmed by pathology review at the Melanoma Center of the University of Pittsburgh Cancer Institute.
All subjects have to be HLA-A2 positive (required for immunologic testing).
Subjects must have recovered fully from surgery.
Availability of resectable or tissue banked tumor cells for autologous tumor dendritic cell vaccine preparation.
Sufficient number of tumor cells available for autologous tumor dendritic cell vaccine preparation (min 2.6 x 10 7).
Sufficient number of DCs of at least 12 X 10 6 for preparation of the autologous tumor dendritic cell vaccine preparation (if less than needed number of cells will be obtained by one course of leukopheresis, the second leukopheresis will be repeated 2 weeks apart).
Subjects must not have received any chemotherapy or immunotherapy within the four weeks preceding vaccination (six weeks for nitrosourea, mitomycin).
Subjects must have an expected survival of greater than or equal to 12 months.
Subjects must have an ECOG performance status 0 or 1.
Subjects must have the following initial and subsequent pretreatment
laboratory parameters: Granulocytes >=2,500/mm3 Lymphocytes >=1000/mm3 Platelets >100,000/mm3 Serum Creatinine <=1.5 X the ULN AST, ALT, GGT, LDH, Alk phos <= 2.5 X the ULN Serum Bilirubin <=1.5 X ULN
Subjects must be >= 18 years of age and must be able to understand the written informed consent.
No evidence of active infection, regardless of the degree of severity or localization. Subjects with active infections (whether or not they require antibiotic therapy) may be eligible after complete resolution of the infection. Subjects on antibiotic therapy must be off antibiotics for at least 7 days before beginning treatment.
Subjects with measurable disease must have an evaluation for extent of disease (tumor staging) performed within 30 days of start of treatment.
Pretreatment baseline evaluations for laboratory parameters must be obtained within 10 to18 days of subject registration

Exclusion Criteria:

Subjects currently treated with anti inflammatory agents including glucocorticoid therapy are ineligible.
Subjects currently on treatment with steroids are ineligible, but may receive the DC autologous tumor dendritic cell vaccine 4 weeks after steroid cessation. Subjects on maintenance steroids because of adrenal insufficiency are eligible.
Subjects with severely abnormal liver function tests [AST (SGOT), ALT (SGPT), GGT, Alk.Phos, LDH, and total bilirubin greater than 2 X ULN].
Subjects with uncontrolled pain.
Subjects with autoimmune disease, HIV, and hepatitis
Subjects with symptomatic brain metastasis.
Subjects with active prior malignancy (with exception of non-melanoma skin cancers and carcinoma in situ of the cervix).
Subjects who have been previously immunized with melanoma vaccine until 10 subjects have been registered in each treatment arm.
Subjects who are pregnant.
Subjects who have sensitivity to drugs to provide local anesthesia.

Sites / Locations

Upmc Upci Hcc

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Vaccine co-cultured with melanoma cells

Vaccine pulsed with tumor cell lysates

Vaccine fused with tumor cells

Arm Description

Dendritic Cells co-cultured with melanoma cells injected as a vaccine intra/peri-nodally under ultrasound guidance

Dendritic Cells pulsed with tumor cell lysates were injected as a vaccine intra/peri-nodally under ultrasound guidance

Dendritic Cells fused with tumor cells were injected as a vaccine intra/peri-nodally under ultrasound guidance

Outcomes

Primary Outcome Measures

Delayed Type Hypersensitivity (DTH) Response

Delayed type hypersensitivity (DTH) response to antigen-loaded autologous, dendritic cell vaccine (DC) injected intradermal in vivo

ELISpot Response to Melanoma

Peripheral blood CD8+ and CD4+ T cell responses against autologous tumor cells, and HLA-presented melanoma epitopes, using ELISPOT and MHC-peptide tetramer assays.

Secondary Outcome Measures

Full Information

NCT ID

NCT01042366

First Posted

January 4, 2010

Last Updated

July 16, 2017

Sponsor

John Kirkwood

Collaborators

National Institutes of Health (NIH), National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01042366

Brief Title

Dendritic Cells (DC) Vaccine for Metastatic Melanoma

Official Title

Randomized Phase II Evaluation of Immunization Against Tumor Cells in Subjects With Metastatic Melanoma Using Autologous Mature Dendritic Cells

Study Type

Interventional

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Terminated

Why Stopped

Closed to accrual in March 2009 for slow accrual.

Study Start Date

October 2002 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

John Kirkwood

Collaborators

National Institutes of Health (NIH), National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to determine what effect using an experimental tumor vaccine (a substance or group of substances meant to cause the immune system to respond to a tumor) made using patients' own tumor cells and blood cells will have on their melanoma.

Detailed Description

Historically, metastatic melanoma has been associated with a poor prognosis. Recently, numerous immunotherapeutic agents, particularly checkpoint inhibitors, have moved to the forefront of therapy. Checkpoint inhibitors such as ipilimumab, pembrolizumab, and nivolumab have revolutionized the treatment of melanoma. Despite this, not all patients respond to checkpoint inhibitors, and even patients who initially respond to checkpoint inhibitor therapy often later relapse (median response duration of 2 years); complete responses remain uncommon. Thus, more effective immunotherapies are clearly needed. The concept of administering dendritic cell (DC)-based vaccines to prompt an immune response against tumor cells has shown promise in the treatment of advanced cancers. Sipuleucel-T, now FDA-approved for the treatment of advanced prostate cancer, is one such vaccine that consists of autologous antigen-presenting cell (APC) activated ex vivo by a fusion protein consisting of the antigen prostatic acid phosphatase (PAP) and granulocyte-macrophage colony stimulating factor (GM-CSF). Although response rates to Sipuleucel-T are low, recent studies suggest that DC vaccines have the potential to improve survival by increasing the breadth and diversity of melanoma-specific T cells. It is known that the method of antigen (Ag) delivery is important for the success of DC vaccines, but it remains unclear which method is most effective in producing antitumor responses. Approaches tested clinically include pulsing with HLA-restricted defined peptide Ags, loading with purified proteins, transfecting with mRNA, engineering with Ag-encoding viral vectors, and using autologous tumor cells or allogeneic cell lines directly as sources of Ag. Efficacy can be measured in vivo using surrogate endpoints, such as development of tumor-specific delayed-type hypersensitivity (DTH) reactions. Prolonged survival of vaccinated melanoma patients has been reported to correlate with induction of positive DTH tests. Antitumor activity may also be assessed by ELISpot analysis of the frequency of tumor-Ag specific IFNγ-producing T cells. To assess the quality of the DC vaccines, surrogate markers of DC function including maturation markers, co-stimulatory molecule expression, and IL12p70 production, a critical cytokine in antitumor response, can be measured

6. Conditions and Keywords

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

Metastatic Melanoma

Keywords

Melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vaccine co-cultured with melanoma cells

Arm Type

Experimental

Arm Description

Dendritic Cells co-cultured with melanoma cells injected as a vaccine intra/peri-nodally under ultrasound guidance

Arm Title

Vaccine pulsed with tumor cell lysates

Arm Type

Experimental

Arm Description

Dendritic Cells pulsed with tumor cell lysates were injected as a vaccine intra/peri-nodally under ultrasound guidance

Arm Title

Vaccine fused with tumor cells

Arm Type

Experimental

Arm Description

Dendritic Cells fused with tumor cells were injected as a vaccine intra/peri-nodally under ultrasound guidance

Intervention Type

Biological

Intervention Name(s)

Vaccination

Intervention Description

Subjects will receive as an outpatient 4 weekly ultrasound-guided intra/peri-lymph nodal administrations of the autologous tumor dendritic cell vaccine. The dose of the autologous tumor cell dendritic cells/vaccine will be 1-5 X 106.

Primary Outcome Measure Information:

Title

Delayed Type Hypersensitivity (DTH) Response

Description

Delayed type hypersensitivity (DTH) response to antigen-loaded autologous, dendritic cell vaccine (DC) injected intradermal in vivo

Time Frame

12 mo

Title

ELISpot Response to Melanoma

Description

Peripheral blood CD8+ and CD4+ T cell responses against autologous tumor cells, and HLA-presented melanoma epitopes, using ELISPOT and MHC-peptide tetramer assays.

Time Frame

12 mo

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects must have Stage III-IV melanoma (any tumor thickness and any number of lymph node involvement, and in-transit metastases, or distant metastases) (AJCC). Each diagnosis will be confirmed by pathology review at the Melanoma Center of the University of Pittsburgh Cancer Institute. All subjects have to be HLA-A2 positive (required for immunologic testing). Subjects must have recovered fully from surgery. Availability of resectable or tissue banked tumor cells for autologous tumor dendritic cell vaccine preparation. Sufficient number of tumor cells available for autologous tumor dendritic cell vaccine preparation (min 2.6 x 10 7). Sufficient number of DCs of at least 12 X 10 6 for preparation of the autologous tumor dendritic cell vaccine preparation (if less than needed number of cells will be obtained by one course of leukopheresis, the second leukopheresis will be repeated 2 weeks apart). Subjects must not have received any chemotherapy or immunotherapy within the four weeks preceding vaccination (six weeks for nitrosourea, mitomycin). Subjects must have an expected survival of greater than or equal to 12 months. Subjects must have an ECOG performance status 0 or 1. Subjects must have the following initial and subsequent pretreatment laboratory parameters: Granulocytes >=2,500/mm3 Lymphocytes >=1000/mm3 Platelets >100,000/mm3 Serum Creatinine <=1.5 X the ULN AST, ALT, GGT, LDH, Alk phos <= 2.5 X the ULN Serum Bilirubin <=1.5 X ULN Subjects must be >= 18 years of age and must be able to understand the written informed consent. No evidence of active infection, regardless of the degree of severity or localization. Subjects with active infections (whether or not they require antibiotic therapy) may be eligible after complete resolution of the infection. Subjects on antibiotic therapy must be off antibiotics for at least 7 days before beginning treatment. Subjects with measurable disease must have an evaluation for extent of disease (tumor staging) performed within 30 days of start of treatment. Pretreatment baseline evaluations for laboratory parameters must be obtained within 10 to18 days of subject registration Exclusion Criteria: Subjects currently treated with anti inflammatory agents including glucocorticoid therapy are ineligible. Subjects currently on treatment with steroids are ineligible, but may receive the DC autologous tumor dendritic cell vaccine 4 weeks after steroid cessation. Subjects on maintenance steroids because of adrenal insufficiency are eligible. Subjects with severely abnormal liver function tests [AST (SGOT), ALT (SGPT), GGT, Alk.Phos, LDH, and total bilirubin greater than 2 X ULN]. Subjects with uncontrolled pain. Subjects with autoimmune disease, HIV, and hepatitis Subjects with symptomatic brain metastasis. Subjects with active prior malignancy (with exception of non-melanoma skin cancers and carcinoma in situ of the cervix). Subjects who have been previously immunized with melanoma vaccine until 10 subjects have been registered in each treatment arm. Subjects who are pregnant. Subjects who have sensitivity to drugs to provide local anesthesia.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John M Kirkwood, MD

Organizational Affiliation

UPMC UPCI HCC

Official's Role

Principal Investigator

Facility Information:

Facility Name

Upmc Upci Hcc

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15232

Country

United States

12. IPD Sharing Statement

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Dendritic Cells (DC) Vaccine for Metastatic Melanoma

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