Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma

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

Vaccination Of HLA-A1 And/Or -A2+ Stage III or IV Melanoma Patients With Tumor Peptide - Loaded Autologous Dendritic Cells That Are Generated In The Absence Or Presence Of CD40 Ligand

RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage III or stage IV melanoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the efficacy of vaccination with autologous dendritic cells pulsed with tumor and influenza antigen peptides treated with vs without ex vivo CD40-ligand, in terms of tumor-specific T-cell response, in patients with HLA-A1 and/or HLA-A2.1 positive stage III or IV melanoma.
  • Determine the safety and tolerability of these vaccinations in these patients.
  • Determine tumor response and recurrence rates in patients treated with these vaccinations.

OUTLINE: This is an open-label non-randomized study.

  • Phase I: Patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMC). PBMC are cultured with sargramostim (GM-CSF) and interleukin-4 to generate dendritic cells (DCs) on day -9. DCs are pulsed separately with HLA-A1 and HLA-A2.1-restricted flu matrix peptides derived from melanoma-associated tumor antigens (MAGE-10.A2, Melan-A, MAGE-3, NY-ESO-1, gp100 antigen, and tyrosinase peptide). Half of the DCs are treated ex vivo with CD40-ligand. Patients receive the peptide-pulsed DC vaccinations subcutaneously (SC) on days 1, 14, 42, and 70 in the absence of disease progression.

Patients who show tumor response (at least stable disease) at day 98 progress to phase II of the study.

  • Phase II: Patients undergo leukapheresis as in phase I on days 102, 352, and 688. Patients receive up to 6 additional booster vaccinations SC as in phase I on days 126, 184, 268, 356, 520, 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)

62

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

  • Germany
      • 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 stage III or IV cutaneous malignant melanoma

  • HLA-A1 and/or HLA-A2 expression by serologic HLA typing

    • HLA-A2.1 subtype must be confirmed by polymerase chain reaction on genomic DNA obtained from peripheral blood mononuclear cells
  • No active CNS metastases by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

  • Over 18

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 disorders

Hepatic

  • Bilirubin less than 2.0 mg/dL
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody negative

Renal

  • Creatinine less than 2.5 mg/dL

Cardiovascular

  • No clinically significant heart disease

Pulmonary

  • No clinically significant respiratory disease

Immunologic

  • No active systemic infection

  • No immunodeficiency disease

    • No evidence of HIV-1, HIV-2, or human T-cell lymphotropic virus-1

  • No active autoimmune disease including (but not limited to):

    • Lupus erythematosus
    • Autoimmune thyroiditis or uveitis
    • Multiple sclerosis
    • Inflammatory bowel disease

Other

  • Stable medical condition
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 1 month after study participation
  • No organic brain syndrome or psychiatric illness that would preclude study compliance
  • No other concurrent active malignancy
  • No other concurrent serious illness that would preclude study treatment
  • No contraindication to leukapheresis

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 4 weeks since prior immunotherapy
  • No other concurrent immunotherapy

Chemotherapy

  • More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas)
  • No concurrent chemotherapy

Endocrine therapy

  • No concurrent corticosteroids

Radiotherapy

  • More than 4 weeks since prior radiotherapy
  • No prior radiotherapy to the spleen
  • Concurrent palliative radiotherapy allowed

Surgery

  • Recovered from prior surgery
  • No prior splenectomy
  • No prior organ allograft
  • Concurrent surgery on selected metastases (e.g., because of pain or local complications such as compression) allowed

Other

  • No other concurrent investigational drugs
  • No concurrent participation in another clinical trial

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: Non-Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety
Tolerability
Comparison of the efficacy of vaccination with vs without ex vivo CD40-ligand in terms of tumor-specific T-cell response

Secondary Outcome Measures

Outcome Measure
Tumor response
Recurrence rates

Collaborators and Investigators

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

Sponsor

University Hospital Erlangen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

October 1, 2002

Primary Completion (Actual)

June 1, 2005

Study Completion (Actual)

June 1, 2007

Study Registration Dates

First Submitted

January 27, 2003

First Submitted That Met QC Criteria

January 27, 2003

First Posted (Estimate)

January 28, 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

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000258491
  • ERLANGEN-1490
  • EU-20232

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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