Vaccine Therapy in Treating Patients With Stage IV Cutaneous Melanoma

May 11, 2015 updated by: PD Dr. med. univ. Beatrice Schuler-Thurner, University Hospital Erlangen

Vaccination of Stage IV Cutaneous Melanoma Patients With Mature, Autologous Monocyte-Derived Dendritic Cells Transfected With RNAs Encoding for Mage-3, MelanA, and Survivin Antigens

RATIONALE: Vaccines made from a person's dendritic cells and antigens may make the body build an immune response to kill tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy using autologous dendritic cells with antigens in treating patients who have stage IV cutaneous melanoma.

Study Overview

Detailed Description

OBJECTIVES:

Primary

  • Determine the safety and tolerability of vaccination with autologous monocyte-derived dendritic cells (DC) transfected with RNAs encoding Melan-A, MAGE-3, and survivin antigens in patients with stage IV cutaneous melanoma.
  • Determine whether tumor antigen-specific T-cell responses are induced in patients treated with this vaccine.
  • Determine whether simultaneous loading of DC with keyhole limpet hemocyanin (KLH) significantly enhances induction of the Melan-A, MAGE-3, and survivin antigens in these patients.

Secondary

  • Determine clinical antitumor activity (e.g., objective tumor response, time to tumor progression, progression-free interval, and overall survival) in patients treated with this vaccine.

OUTLINE: This is an open-label, nonrandomized study.

  • Phase I: Beginning 9-11 days before vaccination, patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMCs). PBMCs are processed for the generation of dendritic cells (DC) to be used for vaccinations. PBMCs are transfected with RNAs encoding for Melan-A, MAGE-3, and survivin antigens. DC are pulsed with keyhole limpet hemocyanin (KLH) for some patients.

Patients receive antigen-pulsed (with or without KLH) DC vaccination subcutaneously (SC) on days 1, 15, 43, and 71 in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may proceed to the phase II portion of the study.

  • Phase II: Patients undergo leukapheresis as in phase I on days 102, 354, and 690. Patients receive up to 6 additional booster vaccinations SC as in phase I on days 127, 185, 269, 356, 521, and 692.

Patients are followed for 10 years.

PROJECTED ACCRUAL: A total of 8-30 patients will be accrued for this study within 6-12 months.

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Erlangen, Germany, D-91052
        • Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed cutaneous* melanoma

    • Stage IV
  • Incurable by surgical resection
  • Progressive disease after at least 1 standard chemotherapy or chemoimmunotherapy regimen (e.g., dacarbazine or cisplatin monotherapy)
  • Unidimensionally or bidimensionally measurable disease by physical examination (e.g., cutaneous metastases) and/or noninvasive radiological procedures
  • No active CNS metastases by CT scan or MRI

    • Previously treated (e.g., excision of a single metastasis) CNS metastases are allowed provided there are no signs of active CNS metastases NOTE: *Metastatic melanoma with unidentified primary tumor allowed provided an ocular melanoma can be definitely excluded and origin from the skin is likely

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Karnofsky 60-100%

Life expectancy

  • At least 4 months

Hematopoietic

  • WBC greater than 2,500/mm^3
  • Neutrophil count greater than 1,000/mm^3
  • Lymphocyte count greater than 700/mm^3
  • Platelet count greater than 75,000/mm^3
  • Hemoglobin greater than 9 g/dL
  • No bleeding disorder

Hepatic

  • Bilirubin less than 2.0 mg/dL
  • No evidence of hepatitis B or C infection

Renal

  • Creatinine less than 2.5 mg/dL

Cardiovascular

  • No clinically significant heart disease

Pulmonary

  • No respiratory disease

Immunologic

  • HIV-1 and HIV-2 negative
  • HTLV-1 negative
  • No active systemic infection
  • No immunodeficiency disease
  • No active autoimmune disease (e.g., lupus erythematosus, autoimmune thyroiditis or uveitis, multiple sclerosis, or inflammatory bowel disease)

    • Vitiligo allowed

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 4 weeks after study participation
  • Stable medical condition
  • No other major serious illness
  • No contraindication to leukapheresis
  • No organic brain syndrome or significant psychiatric abnormality that would preclude study participation or follow-up
  • No other active malignant neoplasm

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 4 weeks since prior immunotherapy
  • No other concurrent immunotherapy during and for 2 weeks after study participation

Chemotherapy

  • More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas [e.g., fotemustine])
  • No concurrent chemotherapy during and for 2 weeks after study participation

Endocrine therapy

  • No concurrent corticosteroids during and for 2 weeks after study participation

Radiotherapy

  • More than 2 weeks since prior radiotherapy
  • No prior radiotherapy to the spleen
  • Concurrent palliative radiotherapy to selected metastases (e.g., due to pain or local complications such as compression) is allowed

Surgery

  • Recovered from prior surgery
  • No prior splenectomy
  • No prior organ allografts
  • Concurrent surgical therapy to selected metastases (e.g., due to pain or local complications such as compression) is allowed

    • Selected accessible metastases may be removed for tumor infiltrating lymphocyte assay or other immunomonitoring investigations (e.g., expression of tumor antigens and HLA molecules)

Other

  • No other concurrent investigational drug or paramedical substance during and for 2 weeks after study participation
  • No concurrent participation in another clinical trial
  • Concurrent palliative medication allowed (e.g., acetaminophen, indomethacin, or opiates)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety and tolerability at every visit
Time Frame: 3 months
3 months
Overall survival as assessed by clinical staging (CT scan, positron emission tomography [PET]) every 3 months
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Time to progression as assessed by clinical staging (CT scan, PET) every 3 months
Time Frame: 3 months
3 months
Objective tumor response as assessed by clinical staging (CT scan, PET) every 3 months
Time Frame: 3 months
3 months
Duration of response as assessed by clinical staging (CT scan, PET) every 3 months
Time Frame: 3 months
3 months
Induction of antigen-specific immune responses as assessed by elispot and tetramer staining at every visit
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Gerold Schuler, Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2003

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

December 10, 2003

First Submitted That Met QC Criteria

December 10, 2003

First Posted (Estimate)

December 11, 2003

Study Record Updates

Last Update Posted (Estimate)

May 12, 2015

Last Update Submitted That Met QC Criteria

May 11, 2015

Last Verified

May 1, 2015

More Information

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.

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