Vaccine Treatment for Advanced Malignant Melanoma
This 2-phase study will determine the safety of treating patients with malignant melanoma with the genetically engineered HyperAcute-Melanoma vaccine. It will establish the proper vaccine dose and will examine side effects and potential benefits of the treatment. The vaccine contains killed melanoma cells containing a mouse gene that causes the production of a foreign pattern of protein-sugars on the cell surface. It is hoped that the immune response to the foreign substance will stimulate the immune system to attack the patient's own cancer cells that have similar proteins without this sugar pattern, causing the tumor to remain stable or shrink.
Patients 18 years of age or older with malignant melanoma may be eligible for this study. Candidates will be screened with medical history and physical examination, blood tests, urinalysis, chest x-rays and CT scans. MRI, PET, and ultrasound scans may be obtained if needed.
Participants will receive twelve vaccinations two weeks apart from each other. The vaccines will be injected under the skin, similar to the way a tuberculosis skin test is given. Phase I of the study will treat successive groups of patients with increasing numbers of the vaccine cells to evaluate side effects of the treatment and determine the optimum dose. Phase II will look for any beneficial effects of the vaccine given at the highest dose found to be safe in Phase I. Monthly blood samples will be drawn during the 6 months of vaccine treatment. In addition, patient follow-up visits will be scheduled every 3 months for the remaining first year (6 months) after vaccination and then every 6 months for the next 2 years for the following tests and procedures to evaluate treatment response and side effects:
Medical history and physical examination Blood tests X-rays and various scans (nuclear medicine/CT/MRI) FACT-G Assessment questionnaire to measure the impact of treatment on the patient's general well-being. The questionnaire is administered before beginning treatment, monthly during treatment, and during follow-up visits after completing the treatment. It includes questions on the severity of cancer symptoms and the ability to perform normal activities of daily life.
Biological: HyperAcute-Melanoma Vaccine
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Dorgenmeltucel-L (HyperAcute Melanoma) an Antitumor Vaccination Using Alpha(1,3)Galactosyltransferase Expressing Allogeneic Tumor Cells in Patients With Refractory or Recurrent Malignant Melanoma|
- To assess the side effects, dose-limiting toxicity and maximum tolerated dose. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- To assess tumor response and immunological response. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||March 2006|
|Study Completion Date:||September 2007|
|Primary Completion Date:||September 2007 (Final data collection date for primary outcome measure)|
|Experimental: vaccine group||
Biological: HyperAcute-Melanoma Vaccine
Cells will be injected intradermally every two weeks for twelve vaccinations. If the patient completes all twelve vaccinations, dosage will vary from a total of 1.3 x 109 to 3.8 x 109 HyperAcute™-Melanoma Vaccine cells administered.
Other Name: HAM-1, HAM-2, and HAM-3
According to statistics of the American Cancer Society, an estimated 55,000 individuals will be diagnosed with malignant melanoma and 8,000 will die of the disease this year in the Unites States despite all current therapy. This protocol attempts to exploit an approach to melanoma vaccine therapy using a naturally occurring barrier to xenotransplantation in humans in attempt to vaccinate patients against their melanoma The expression of the murine alpha(1,3)galactosyltransferase [alpha(1,3)GT] gene results in the cell surface expression of alpha(1,3)galactosyl-epitopes (alpha-gal) on membrane glycoproteins and glycolipids. These epitopes are the major target of the hyperacute rejection response that occurs when organs are transplanted from non-primate donor species into man. Human hosts often have pre-existing anti-alpha-gal antibodies that bind alpha-gal epitopes and lead to rapid activation of complement and cell lysis. The pre-existing anti-alpha-gal antibodies found in most individuals are thought to be due to exposure to alpha-gal epitopes that are naturally expressed on normal gut flora leading to chronic immunological stimulation. These antibodies may comprise up to 1% of serum IgG. In this Phase I/II trial, patients with advanced stage melanoma will undergo a series of twelve intradermal injections with a trivalent vaccine composed of irradiated allogeneic melanoma cell lines (HAM-1, HAM-2 and HAM-3). These cell lines have been transduced with a recombinant Moloney murine leukemia virus (MoMLV)-based retroviral vector expressing the murine alpha(1,3)GT gene. Endpoints of the study include determination of dose-limiting toxicity (DLT), maximum tolerated dose (MTD), tumor and immunological responses.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00300612
|United States, Florida|
|H. Lee Moffitt Cancer Center & Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Ronald C. DeConti, M.D.||University of South Florida|
|Study Chair:||Charles J. Link, M.D.||NewLink Genetics Corporation|