CClinicalTrials.gg
CompletedNCT00056134Updated Feb 19, 2018

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

A Phase 1/2 interventional study of Dendritic cell vaccine plus denileukin difitox in Melanoma (Skin), sponsored by University Hospital Erlangen. Completed at 1 site in Germany. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2018-02-19.

Sponsored by University Hospital Erlangen · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
23
Allocation
Not applicable
Ages
18 Years to 120 Years
Sex
All
01

Study 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.

Read the detailed description

OBJECTIVES:

  • 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.

OUTLINE:

  • 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.

02

Conditions studied

  • Melanoma (Skin)

Browse trials for

Keywords

  • recurrent melanoma
  • stage IV melanoma
  • stage IIIA melanoma
  • stage IIIB melanoma
  • stage IIIC melanoma
03

In context

Melanoma

3,006 studies on the registry are indexed under Melanoma; 520 are open to participants now.

This study's enrollment of 23 is below the median of 38 across 2,351 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

University Hospital Erlangen is the lead sponsor of 27 studies on the registry; 3 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 120 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • Over 18

Performance status

  • Karnofsky 60-100%

Life expectancy

  • At least 6 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
  • No hepatitis B or C

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 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

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

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

Chemotherapy

  • 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

Radiotherapy

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

Surgery

  • 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

Other

  • 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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
23 participants (actual)

Interventions

  • BiologicalDendritic cell vaccine plus denileukin difitox
06

What researchers measure

Primary outcomes

  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 outcomes

  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

07

Study locations

1 site
  • Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen
    Erlangen, D-91052, Germany
08

References and documents

Publications

  • Baur AS, 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, Kampgen E, Dudziak D, Steinkasserer A, Cavalieri D, Schuler-Thurner B, Schuler G. Denileukin diftitox (ONTAK) induces a tolerogenic phenotype in dendritic cells and stimulates survival of resting Treg. Blood. 2013 Sep 26;122(13):2185-94. doi: 10.1182/blood-2012-09-456988. Epub 2013 Aug 19. PubMed 23958949 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 19, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00056134
Lead sponsor
University Hospital Erlangen
Responsible party
PD Dr. med. univ. Beatrice Schuler-Thurner (Principal Investigator, University Hospital Erlangen) — Principal investigator
First posted
Mar 7, 2003
Start date
Oct 2002
Primary completion
Oct 2011
Completion
May 2012
Last update
Feb 19, 2018

Study contacts

Gerold Schuler
study chair · Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2018. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion