- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01042366
Dendritic Cells (DC) Vaccine for Metastatic Melanoma
Randomized Phase II Evaluation of Immunization Against Tumor Cells in Subjects With Metastatic Melanoma Using Autologous Mature Dendritic Cells
Study Overview
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
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- Upmc Upci Hcc
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Vaccine co-cultured with melanoma cells
Dendritic Cells co-cultured with melanoma cells injected as a vaccine intra/peri-nodally under ultrasound guidance
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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.
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EXPERIMENTAL: Vaccine pulsed with tumor cell lysates
Dendritic Cells pulsed with tumor cell lysates were injected as a vaccine intra/peri-nodally under ultrasound guidance
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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.
|
EXPERIMENTAL: Vaccine fused with tumor cells
Dendritic Cells fused with tumor cells were injected as a vaccine intra/peri-nodally under ultrasound guidance
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Delayed Type Hypersensitivity (DTH) Response
Time Frame: 12 mo
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Delayed type hypersensitivity (DTH) response to antigen-loaded autologous, dendritic cell vaccine (DC) injected intradermal in vivo
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12 mo
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ELISpot Response to Melanoma
Time Frame: 12 mo
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Peripheral blood CD8+ and CD4+ T cell responses against autologous tumor cells, and HLA-presented melanoma epitopes, using ELISPOT and MHC-peptide tetramer assays.
|
12 mo
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: John M Kirkwood, MD, Upmc Upci Hcc
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UPCI 01-171
- 5P01CA073743 (NIH)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Melanoma
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Mohammed M MilhemGenentech, Inc.TerminatedMelanoma | Metastatic Melanoma | BRAF-mutated Metastatic Melanoma | V600EBRAF-mutated Metastatic MelanomaUnited States
-
National Cancer Institute (NCI)TerminatedMetastatic Uveal Melanoma | Metastatic Ocular MelanomaUnited States
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Delcath Systems Inc.Active, not recruitingMetastatic Uveal Melanoma | Metastatic Ocular MelanomaUnited States
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MorphotekTerminatedMelanoma | Metastatic Melanoma | Advanced Melanoma | Malignant Metastatic MelanomaUnited States
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GlaxoSmithKlineWithdrawnCancer | Metastatic Uveal Melanoma | GNA11 Mutation-positive Metastatic Melanoma | GNAQ Mutation-positive Metastatic Melanoma
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Elizabeth DavisBristol-Myers SquibbTerminatedMetastatic Melanoma | Advanced Melanoma | Metastatic Melanoma Stratified by MHC-II ExpressionUnited States
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Mayo ClinicNational Cancer Institute (NCI)Active, not recruitingMetastatic Melanoma | Metastatic Uveal Melanoma | Unresectable Melanoma | Clinical Stage III Cutaneous Melanoma AJCC v8 | Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 | Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 | Pathologic Stage IIID Cutaneous Melanoma AJCC v8 | Pathologic Stage III Cutaneous... and other conditionsUnited States
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Fred Hutchinson Cancer CenterAmazon.com Services LLCRecruitingAnatomic Stage IV Breast Cancer AJCC v8 | Prognostic Stage IV Breast Cancer AJCC v8 | Metastatic Cutaneous Melanoma | Unresectable Cutaneous Melanoma | Clinical Stage III Cutaneous Melanoma AJCC v8 | Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 | Pathologic Stage IIID Cutaneous Melanoma AJCC... and other conditionsUnited States
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Provectus Biopharmaceuticals, Inc.Active, not recruitingMetastatic Colorectal Cancer | Hepatocellular Carcinoma | Metastatic Lung Cancer | Metastatic Breast Cancer | Metastatic Melanoma | Metastatic Uveal Melanoma | Metastatic Pancreatic Cancer | Metastatic Colon Cancer | Metastatic Ocular Melanoma | Cancer Metastatic to the LiverUnited States
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National Cancer Institute (NCI)Active, not recruitingMetastatic Cutaneous Melanoma | Clinical Stage III Cutaneous Melanoma AJCC v8 | Recurrent Cutaneous Melanoma | Clinical Stage IV Cutaneous Melanoma AJCC v8 | Recurrent Mucosal Melanoma | Metastatic Mucosal Melanoma | Non-Cutaneous Melanoma | Metastatic Non-Cutaneous Melanoma | Recurrent Non-Cutaneous...United States, Canada, Ireland
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