Dendritic Cell Based Therapy of Malignant Melanoma

Original Study ID : MM0413

NCT ID : NCT00197912

Brief Title : Dendritic Cell Based Therapy of Malignant Melanoma

Official Title : Vaccination With Autologous Dendritic Cells Pulsed With Tumor Antigens for Treatment of Patients With Malignant Melanoma.Phase I/II Study.

Brief Summary :

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.

Source : Herlev Hospital

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.

Overall Status : Recruiting

Start Date : September 2004

Official Title : Phase 1/Phase 2

Phase : Interventional

Study Design : Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Enrollment : 25

Verification Date : November 2008

First Received Date : September 12, 2005

Trial Eligibility

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.

Gender : Both

Minimum Age : 18 Years

Maximum Age : N/A

Healthy Volunteers : No

Facilities

Facility Name : Department of Oncology, Copenhagen University Hospital, Herlev

Status : Recruiting

City : Herlev

Zip Code : 2970

Country : Denmark

Refferances

PMID : 14985857

Citation : 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.

OutComes

Primary OutComes

Measure : Primary aim of the study is to evaluate tolerability and safety of the treatment

Time Frame : weekly the first four weeks thereafter biweekly

Safety issue : Yes

Secondary OutComes

Measure : Secondary aims: evaluation of treatment induced immune response and clinical response.

Time Frame : after 8 and 16 weeks

Safety issue : No

Interventions

Type : Biological

Name : tumor antigen loaded autologous dendritic cells

Description : 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.

Clinical Trial Name - Dendritic Cell Based Therapy of Malignant Melanoma