Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy in Treating Patients With Stage IV Cutaneous Melanoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Active 18 and over Other ERLANGEN-DERMA-ER-DC-06 EU-20317, NCT00074230

Objectives

Primary

1. Determine the safety and tolerability of vaccination with autologous monocyte-derived dendritic cells (DC) transfected with RNAs encoding Melan-A, MAGE-3, and survivin antigens in patients with stage IV cutaneous melanoma.
2. Determine whether tumor antigen-specific T-cell responses are induced in patients treated with this vaccine.
3. Determine whether simultaneous loading of DC with keyhole limpet hemocyanin (KLH) significantly enhances induction of the Melan-A, MAGE-3, and survivin antigens in these patients.

Secondary

1. Determine clinical antitumor activity (e.g., objective tumor response, time to tumor progression, progression-free interval, and overall survival) in patients treated with this vaccine.

Entry Criteria

Disease Characteristics:

• Histologically confirmed cutaneous* melanoma
  • Stage IV



• Incurable by surgical resection



• Progressive disease after at least 1 standard chemotherapy or chemoimmunotherapy regimen (e.g., dacarbazine or cisplatin monotherapy)



• Unidimensionally or bidimensionally measurable disease by physical examination (e.g., cutaneous metastases) and/or noninvasive radiological procedures



• No active CNS metastases by CT scan or MRI
  • Previously treated (e.g., excision of a single metastasis) CNS metastases are allowed provided there are no signs of active CNS metastases

 [Note: *Metastatic melanoma with unidentified primary tumor allowed provided an ocular melanoma can be definitely excluded and origin from the skin is likely]

Prior/Concurrent Therapy:

Biologic therapy

• More than 4 weeks since prior immunotherapy
• No other concurrent immunotherapy during and for 2 weeks after study participation

Chemotherapy

• More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas [e.g., fotemustine])
• No concurrent chemotherapy during and for 2 weeks after study participation

Endocrine therapy

• No concurrent corticosteroids during and for 2 weeks after study participation

Radiotherapy

• More than 2 weeks since prior radiotherapy
• No prior radiotherapy to the spleen
• Concurrent palliative radiotherapy to selected metastases (e.g., due to pain or local complications such as compression) is allowed

Surgery

• Recovered from prior surgery
• No prior splenectomy
• No prior organ allografts
• Concurrent surgical therapy to selected metastases (e.g., due to pain or local complications such as compression) is allowed
  • Selected accessible metastases may be removed for tumor infiltrating lymphocyte assay or other immunomonitoring investigations (e.g., expression of tumor antigens and HLA molecules)

Other

• No other concurrent investigational drug or paramedical substance during and for 2 weeks after study participation
• No concurrent participation in another clinical trial
• Concurrent palliative medication allowed (e.g., acetaminophen, indomethacin, or opiates)

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• At least 4 months

Hematopoietic

• WBC greater than 2,500/mm³
• Neutrophil count greater than 1,000/mm³
• Lymphocyte count greater than 700/mm³
• Platelet count greater than 75,000/mm³
• Hemoglobin greater than 9 g/dL
• No bleeding disorder

Hepatic

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

Renal

• Creatinine less than 2.5 mg/dL

Cardiovascular

• No clinically significant heart disease

Pulmonary

• No respiratory disease

Immunologic

• HIV-1 and HIV-2 negative
• HTLV-1 negative
• No active systemic infection
• No immunodeficiency disease
• No active autoimmune disease (e.g., lupus erythematosus, autoimmune thyroiditis or uveitis, multiple sclerosis, or inflammatory bowel disease)
  • Vitiligo allowed

Other

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

Expected Enrollment

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

Outcomes

Safety and tolerability at every visit
Overall survival as assessed by clinical staging (CT scan, positron emission tomography [PET]) every 3 months

Time to progression as assessed by clinical staging (CT scan, PET) every 3 months
Objective tumor response as assessed by clinical staging (CT scan, PET) every 3 months
Duration of response as assessed by clinical staging (CT scan, PET) every 3 months
Induction of antigen-specific immune responses as assessed by elispot and tetramer staining at every visit

Outline

This is an open-label, nonrandomized study.

• Phase I: Beginning 9-11 days before vaccination, patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMCs). PBMCs are processed for the generation of dendritic cells (DC) to be used for vaccinations. PBMCs are transfected with RNAs encoding for Melan-A, MAGE-3, and survivin antigens. DC are pulsed with keyhole limpet hemocyanin (KLH) for some patients.

  Patients receive antigen-pulsed (with or without KLH) DC vaccination subcutaneously (SC) on days 1, 15, 43, and 71 in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may proceed to the phase II portion of the study.




• Phase II: Patients undergo leukapheresis as in phase I on days 102, 354, and 690. Patients receive up to 6 additional booster vaccinations SC as in phase I on days 127, 185, 269, 356, 521, and 692.

Patients are followed for 10 years.

Trial Contact Information

Trial Lead Organizations

Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen

Gerold Schuler, Principal investigator		Ph: 49-9131-85-33164

Germany
	Erlangen
	Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen
		Gerold Schuler	Ph:  49-9131-85-33164

Registry Information
Official Title		Vaccination of Stage IV Cutaneous Melanoma Patients with Mature, Autologous Monocyte-Derived Dendritic Cells Transfected with RNAs Encoding for Mage-3, MelanA, and Survivin Antigens
Trial Start Date		2003-07-10
Registered in ClinicalTrials.gov		NCT00074230
Date Submitted to PDQ		2003-10-28
Information Last Verified		2006-08-15