Vaccine Therapy in Treating Patients With Stage IV Cutaneous Melanoma

NCT ID: NCT00074230

Last Updated: 2015-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31
• Study Completion Date: 2014-03-31

Brief Summary

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.

Detailed 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.

Conditions

Melanoma (Skin)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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

Within cohort 1 patients received the vaccine intradermally; in cohort 2 the route of Administration was intravenous Infusion, half of the patients had additional loading with RNA coding for EL-Selektin; in cohort 3 the vaccines was again infused intravenously, the cells were matured not with MCM.mimic as in cohort 1 and 2 but either with TriMix or MCM-mimic plus CD40L-RNA.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Exclusion Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Erlangen

OTHER

Sponsor Role: lead

Responsible Party

PD Dr. med. univ. Beatrice Schuler-Thurner

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gerold Schuler

Role: PRINCIPAL_INVESTIGATOR

Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen

Locations

Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen

Erlangen, , Germany

Countries

Germany

Other Identifiers

CDR0000343699

Identifier Type: REGISTRY

Identifier Source: secondary_id

EU-20317

Identifier Type: -

Identifier Source: secondary_id

ERLANGEN-DERMA-ER-DC-06

Identifier Type: -

Identifier Source: org_study_id