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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00056134
Recruitment Status : Completed
First Posted : March 7, 2003
Last Update Posted : February 19, 2018
Information provided by (Responsible Party):
PD Dr. med. univ. Beatrice Schuler-Thurner, University Hospital Erlangen

Brief Summary:

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. Biological therapies such as denileukin diftitox may be able to deliver cancer-killing substances directly to melanoma cells. Combining vaccine therapy with biological therapy may kill more tumor cells.

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

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Biological: Dendritic cell vaccine plus denileukin difitox Phase 1 Phase 2

Detailed Description:


  • Compare the efficacy of vaccination with autologous dendritic cells pulsed with tumor and influenza antigen peptides with or without ex vivo CD40-ligand and denileukin diftitox, 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 in patients treated with these vaccinations.


  • Phase I (Administration of denileukin diftitox and vaccinations #1 to #4): Patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PMBC). PBMC are processed for the generation of dendritic cells (DC) to be used for vaccinations. DC are pulsed with HLA-A1- and HLA-A2.1-restricted peptides derived from melanoma-associated tumor antigens. DC are pulsed with or without ex vivo treatment with CD40-ligand. Patients receive denileukin diftitox IV for 3 consecutive days before the first vaccination. Patients receive 4 pulsed DC vaccinations subcutaneously (SC) on days 1, 14, 42, and 70 in the absence of disease progression or unacceptable toxicity.

Patients who show a tumor response (at least stable disease) may receive vaccination #5 and further booster vaccinations.

  • Phase II: DC are generated and pulsed as in phase I. Patients receive up to 6 additional booster pulsed DC vaccinations SC on days 126, 184, 268, 356, 520, and 692 in the absence of disease progession or unacceptable toxicity.

Patients are followed for 10 years.

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Vaccination of HLA-A1 and/or -A2+ Stage III or IV Melanoma Patients With Tumor Peptide-Loaded Autologous Dendritic Cells With Prior Depletion of CD25-Positive Cells Using Denileukin Difitox (ONTAK)
Study Start Date : October 2002
Actual Primary Completion Date : October 2011
Actual Study Completion Date : May 2012

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma Vaccines

Primary Outcome Measures :
  1. Safety and tolerability as assessed by clinical and laboratory evaluation at every visit
  2. Overall survival as assessed by clinical staging (CT scan and positron emission tomography [PET]) every 3 months

Secondary Outcome Measures :
  1. Depletion of regulatory T-cells as assessed by tetramer stainings at every visit
  2. Induction of antigen-specific immune responses as assessed by elispot and tetramer staining at every visit
  3. Time to progression as assessed by clinical staging (CT scan and PET) every 3 months
  4. Objective response rate as assessed by clinical staging (CT scan and PET) every 3 months

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed locoregional or metastatic cutaneous malignant melanoma

    • Stage III or IV disease

      • Stage III: pT4b, N0, M0 (satellite metastases) or any pT, N1 or pT, N1 or N2a-c, M0 (lymph node metastases or in transit intralymphatic metastases)
      • Stage IV: any pT, N1-2, M1a-b
      • Surgically incurable
      • Incurable with standard treatment (i.e., localized chemotherapy/limb perfusion for stage III, systemic chemotherapy for stage IV)
  • Unidimensionally or bidimensionally measurable disease by physical examination (e.g., cutaneous metastases) and/or non-invasive radiologic procedures NOTE: Stage III lesions may be measurable lymph nodes after incomplete resection and/or inoperable in transit metastases
  • HLA-A1 and/or HLA-A2 expression by serologic HLA typing

    • HLA-A2.01 subtype must be confirmed by polymerase chain reaction on genomic DNA obtained from peripheral blood mononuclear cells
  • No active CNS metastases

    • Previously treated CNS metastases (e.g., excision of a single metastasis) allowed if no active disease present by CT scan or MRI



  • Over 18

Performance status

  • Karnofsky 60-100%

Life expectancy

  • At least 6 months


  • 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


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


  • Creatinine less than 2.5 mg/dL


  • No clinically significant heart disease


  • No clinically significant respiratory disease


  • No active systemic infection
  • No immunodeficiency disease

    • No evidence of HIV-1, HIV-2, or human T-cell lymphocytic virus-1
  • No active autoimmune disease including, but not limited to:

    • Lupus erythematosus
    • Autoimmune thyroiditis or uveitis
    • Multiple sclerosis
    • Inflammatory bowel disease NOTE: Vitiligo allowed


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


Biologic therapy

  • More than 4 weeks since prior systemic immunotherapy
  • No concurrent immunotherapy during and for 2 weeks after last vaccination


  • See Disease Characteristics
  • More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas [e.g., fotemustine])
  • No concurrent chemotherapy during and for 2 weeks after last vaccination

Endocrine therapy

  • No concurrent corticosteroids during and for 2 weeks after last vaccination


  • No prior radiotherapy to the spleen
  • Concurrent palliative radiotherapy allowed for selected metastases (e.g., pain or local complications such as compression)


  • See Disease Characteristics
  • Recovered from prior surgery
  • No prior splenectomy
  • No prior organ allografts
  • Concurrent surgery of selected metastases (e.g., pain or local complications such as compression) allowed


  • No other concurrent investigational drugs during and for 2 weeks after last vaccination
  • No concurrent paramedical substance during and for 2 weeks after last vaccination
  • No concurrent participation or intent to participate in another clinical trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00056134

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Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen
Erlangen, Germany, D-91052
Sponsors and Collaborators
University Hospital Erlangen
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Study Chair: Gerold Schuler Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen
Study Data/Documents: Publication  This link exits the site

Denileukin diftitox (ONTAK) induces a tolerogenic phenotype in dendritic cells and stimulates survival of resting Treg.

Baur AS1, Lutz MB, Schierer S, Beltrame L, Theiner G, Zinser E, Ostalecki C, Heidkamp G, Haendle I, Erdmann M, Wiesinger M, Leisgang W, Gross S, Pommer AJ, Kämpgen E, Dudziak D, Steinkasserer A, Cavalieri D, Schuler-Thurner B, Schuler G.

Clinical Study Report  This link exits the site
Identifier: DOI:10.1182/blood-2012-09-4569
Denileukin diftitox (ONTAK) induces... Baur AS et al

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: PD Dr. med. univ. Beatrice Schuler-Thurner, Principal Investigator, University Hospital Erlangen Identifier: NCT00056134    
Other Study ID Numbers: CDR0000270762
First Posted: March 7, 2003    Key Record Dates
Last Update Posted: February 19, 2018
Last Verified: February 2018
Keywords provided by PD Dr. med. univ. Beatrice Schuler-Thurner, University Hospital Erlangen:
recurrent melanoma
stage IV melanoma
stage IIIA melanoma
stage IIIB melanoma
stage IIIC melanoma
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas