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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
PD Dr. med. univ. Beatrice Schuler-Thurner, University Hospital Erlangen
ClinicalTrials.gov Identifier:
NCT00056134
First received: March 6, 2003
Last updated: September 16, 2013
Last verified: September 2013
  Purpose

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 Intervention Phase
Melanoma (Skin)
Biological: denileukin diftitox
Biological: recombinant CD40-ligand
Biological: therapeutic autologous dendritic cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by University Hospital Erlangen:

Primary Outcome Measures:
  • Safety and tolerability as assessed by clinical and laboratory evaluation at every visit [ Designated as safety issue: Yes ]
  • Overall survival as assessed by clinical staging (CT scan and positron emission tomography [PET]) every 3 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Depletion of regulatory T-cells as assessed by tetramer stainings at every visit [ Designated as safety issue: No ]
  • Induction of antigen-specific immune responses as assessed by elispot and tetramer staining at every visit [ Designated as safety issue: No ]
  • Time to progression as assessed by clinical staging (CT scan and PET) every 3 months [ Designated as safety issue: No ]
  • Objective response rate as assessed by clinical staging (CT scan and PET) every 3 months [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: October 2002
Study Completion Date: May 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00056134

Locations
Germany
Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen
Erlangen, Germany, D-91052
Sponsors and Collaborators
University Hospital Erlangen
Investigators
Study Chair: Gerold Schuler Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen
  More Information

Additional Information:
No publications provided by University Hospital Erlangen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: PD Dr. med. univ. Beatrice Schuler-Thurner, Principal Investigator, University Hospital Erlangen
ClinicalTrials.gov Identifier: NCT00056134     History of Changes
Other Study ID Numbers: CDR0000270762, ERLANGEN-ONTAK, EU-20246
Study First Received: March 6, 2003
Last Updated: September 16, 2013
Health Authority: Germany: Paul Ehrlich Institut, Langen

Keywords provided by University Hospital Erlangen:
recurrent melanoma
stage IV melanoma
stage IIIA melanoma
stage IIIB melanoma
stage IIIC melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Denileukin diftitox
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 23, 2014