Dendritic Cell Based Therapy of Malignant Melanoma

Advanced Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00197912
• Other study ID #: MM0413
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 12, 2005
• Last updated: April 23, 2010
• Start date: September 2004
• Est. completion date: April 2010

Study information

• Verified date: July 2009
• Source: Herlev Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Melanoma
• Melanoma

Intervention

Biological:
• tumor antigen loaded autologous dendritic cells
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.

Locations

Country	Name	City	State
Denmark	Department of Oncology, Copenhagen University Hospital, Herlev	Herlev

Sponsors (1)

Lead Sponsor	Collaborator
Herlev Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary aim of the study is to evaluate tolerability and safety of the treatment		weekly the first four weeks thereafter biweekly	Yes
Secondary	Secondary aims: evaluation of treatment induced immune response and clinical response.		after 8 and 16 weeks	No