Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma - Full Text View

Sponsored by:	Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00053391

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.

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

Condition	Intervention	Phase
Melanoma (Skin)	Biological: recombinant CD40-ligand Biological: therapeutic autologous dendritic cells	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: CD40 Ligand

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Comparison of the efficacy of vaccination with vs without ex vivo CD40-ligand in terms of tumor-specific T-cell response [ Designated as safety issue: No ]
Safety [ Designated as safety issue: Yes ]
Tolerability [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Tumor response [ Designated as safety issue: No ]
Recurrence rates [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	October 2002

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00053391

Locations

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

Sponsors and Collaborators

Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen

Investigators

Study Chair:

Gerold Schuler

Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000258491, ERLANGEN-1490, EU-20232
Study First Received:	January 27, 2003
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00053391 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage III melanoma
stage IV melanoma
recurrent melanoma

Study placed in the following topic categories:

Neuroectodermal Tumors
Nevus, Pigmented
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma

Nevus
Recurrence
Neuroendocrine Tumors
Melanoma

Additional relevant MeSH terms:

Neuroectodermal Tumors
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue
Nevi and Melanomas
Neuroendocrine Tumors
Melanoma

ClinicalTrials.gov processed this record on September 11, 2009