Vaccine Therapy in Treating Patients With Stage IV Cutaneous Melanoma

University Hospital Erlangen

Status and phase

Completed

Phase 2

Phase 1

Conditions

Melanoma (Skin)

Treatments

Biological: Autologous Dendritic Cells loaded with MAGE-A3, MelanA and Survivin

Study type

Interventional

Funder types

Other

Identifiers

NCT00074230

EU-20317

CDR0000343699 (Registry Identifier)

ERLANGEN-DERMA-ER-DC-06

Details and patient eligibility

About

RATIONALE: Vaccines made from a person's dendritic cells and antigens may make the body build an immune response to kill tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy using autologous dendritic cells with antigens in treating patients who have stage IV cutaneous melanoma.

Full description

OBJECTIVES:

Primary

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.
Determine whether tumor antigen-specific T-cell responses are induced in patients treated with this vaccine.
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

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.

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.

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

Enrollment

82 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

PATIENT CHARACTERISTICS:

Age

18 and over

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 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

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)