Dendritic Cell Based Therapy of Malignant Melanoma - Full Text View

Sponsor:	Herlev Hospital
Information provided by:	Herlev Hospital
ClinicalTrials.gov Identifier:	NCT00197912

Purpose

The aim of the study is to show if vaccination with autologous dendritic cells pulsed with peptides or tumor lysate in combination with adjuvant cytokines and Cyclophosphamide can induce a measurable immune response in patients with metastatic malignant melanoma, and to evaluate the clinical effect (objective response rate) of the vaccination regime.

Condition	Intervention	Phase
Advanced Melanoma	Biological: tumor antigen loaded autologous dendritic cells	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Vaccination With Autologous Dendritic Cells Pulsed With Tumor Antigens for Treatment of Patients With Malignant Melanoma. Phase I/II Study

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Cyclophosphamide Interleukin-2 Celecoxib

U.S. FDA Resources

Further study details as provided by Herlev Hospital:

Primary Outcome Measures:

Primary aim of the study is to evaluate tolerability and safety of the treatment [ Time Frame: weekly the first four weeks thereafter biweekly ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Secondary aims: evaluation of treatment induced immune response and clinical response. [ Time Frame: after 8 and 16 weeks ] [ Designated as safety issue: No ]

Enrollment:	25
Study Start Date:	September 2004
Study Completion Date:	April 2010
Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Intervention Details:

DC vaccination regime consists of primary 10 intradermal injections of 1-2 weeks interval (q1w x 4 → q2w x 6). HLA-A2 positive patients are treated with p53, survivin and telomerase peptide-pulsed dendritic cells, and HLA-A2 negative patients are treated with allogeneic tumor lysate pulsed dendritic cells. 50 mg cyclophosphamide (Sendoxan®, Baxter A/S) is administered p.o. twice a day bi-weekly and 200 mg celecoxib (Celebra®, Pfizer) is given p.o. every day. From the 2nd vaccine, 2 MIU Interleukin-2 is administered s.c. on day 2-6.

Other Names:

Dendritic cell vaccine
Cyclophosphamide, Sendoxan®, Baxter A/S
Celecoxib, Celebra®, Pfizer
Interleukin-2, Proleukin®, Chiron B.V.

Detailed Description:

Eligible patients receive vaccination with tumor antigen pulsed autologous monocyte-derived mature dendritic cells with a fixed interval. The dendritic cells are generated from leukapheresis products and frozen after antigen loading.

HLA A2 positive patients are treated with PADRE and oncopeptide pulsed DC; p53, survivin and telomerase peptides. HLA A2 negative patients are treated with KLH and tumorlysate pulsed DC; autologous or allogeneic. Each patient is given 6 immunizations with at least 5x106 peptide/lysate pulsed autologous DC. Vaccination 1-4 is given weekly and 4-6 at 2-week intervals. Those patients who exhibit stable disease, partial response or complete response after 6 injections will be given 4 more vaccinations at 2-week interval. The vaccine is applied by intradermal injection near the inguinal region.

IL-2 2 MIU s.c. day 2-6, Cyclophosphamide (Sendoxan®, Baxter A/S) 50 mg twice a day bi-weekly and 200 mg Celecoxib (Celebra®, Pfizer) daily are used. Scans and re-staging tests are performed at scheduled intervals throughout the study.

Eligibility

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

Criteria

Inclusion Criteria:

Histologically proven progressive metastatic or locally advanced melanoma
No standard treatment indicated
Age: > 18
WHO-Performance Status 0-1
At least tone measurable tumor lesions according to the RECIST criteria.
Life expectancy more than 3 months
Acceptable CBC and blood chemistry results
Written informed consent

Exclusion Criteria:

Patients with a history of any other neoplastic disease less than 5 years ago (excepting treated carcinomas in situ of the cervix and basal/squamous cell carcinomas of the skin).
Patients with metastatic disease in the central nervous system (CNS).
Patients with other significant illness including severe allergy, asthma, angina pectoris or congestive heart failure.
Patients with acute or chronic infection including HIV, hepatitis and tuberculosis.
Patients who are pregnant.
Patients who have received antineoplastic therapy including chemotherapy or immunotherapy less than 4 weeks before beginning the trial.
Patients who receive corticosteroids or other immunosuppressive agents.
Baseline serum LDH greater than 2.5 times the upper limit of normal.
Patients with active autoimmune diseases such as lupus erythematosus, rheumatoid arthritis or thyroiditis.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00197912

Locations

Denmark
Department of Oncology, Copenhagen University Hospital, Herlev
Herlev, Denmark, 2970

Sponsors and Collaborators

Herlev Hospital

Investigators

Principal Investigator:

Inge Marie Svane, MD, PHD

Department of Oncology, Copenhagen University Hospital, Herlev, Herlev Ringvej 75, DK-2760 Herlev, Denmark

More Information

Publications:

Svane IM, Pedersen AE, Johnsen HE, Nielsen D, Kamby C, Gaarsdal E, Nikolajsen K, Buus S, Claesson MH. Vaccination with p53-peptide-pulsed dendritic cells, of patients with advanced breast cancer: report from a phase I study. Cancer Immunol Immunother. 2004 Jul;53(7):633-41. Epub 2004 Feb 25.

Responsible Party:	Inge Marie Svane, MD, PhD, Department of Oncology, Herlev Hospital
ClinicalTrials.gov Identifier:	NCT00197912 History of Changes
Other Study ID Numbers:	MM0413
Study First Received:	September 12, 2005
Last Updated:	April 23, 2010
Health Authority:	Denmark: Danish Medicines Agency

Keywords provided by Herlev Hospital:

dendritic cell
cancer vaccine
cyclophosphamide
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
Cyclophosphamide
Interleukin-2
Celecoxib
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012