Determine Toxicity and Antibody Responses With a KLH Conjugated Bivalent Vaccine Containing GD2 Lactone, GD3 Lactone With Immunological Adjuvant QS-DG or OPT-821 in Patients With Disease Free AJCC Stage III or IV Cutaneous Melanoma
Vaccines contain substances that help us make antibodies. Different antibodies help protect us against a variety of harmful things. GD2 and GD3 gangliosides are substances found on the surface of most melanoma cells. They are also occasionally found on some normal cells. Large quantities of antibodies called monoclonal antibodies have been prepared in the laboratory against GD2 and GD3 and given to patients with metastatic melanoma. In about 10% of cases this has resulted in clinically relevant regression of melanomas. These monoclonal antibodies are not currently available or used in the clinic but studies in the laboratory indicate that vaccines against GD2 and GD3 can be as effective as monoclonal antibodies.
In this trial we wish to raise the level of antibodies in your blood against GD2 and GD3. We will vaccinate you with the modified forms of GD2 called GD2 lactone and GD3 called GD3 lactone (GD3L), all attached to the antibody booster KLH, and mixed with the immune booster (immunologic adjuvant) QS-DG. While over a thousand patients have received vaccines with QS-21, the QS-DG used here is synthesized for the first time at MSKCC and is referred to as QS-DG rather than QS-21 which is purified from tree bark. QS-21 and QS-DG are, to the best of our knowledge chemically identical. It is unknown if using this bivalent vaccine will raise the level of antibodies in your blood to either ganglioside. It is unknown if raising the level of antibodies in your blood will lower your risk of relapse. This study will check your blood for production of antibodies, and check you for side effects.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Trials With a KLH Conjugated Bivalent GangliosideVaccine Mixed With Immunological Adjuvants QS-DG or OPT-821in Patients With Disease Free AJCC Stage III or IV|
- Determine the toxicity associated with a bivalent vaccine containing GD2 lactone (GD2L) and GD3 lactone (GD3L) covalently attached to the immunological carrier protein keyhole limpet hemocyanin (KLH), plus the immunological adjuvant QS-21 and OPT-821. [ Time Frame: conclusion of study ] [ Designated as safety issue: Yes ]
- Evaluate the antibody response following vaccination with the bivalent vaccine plus QS-DG or OPT-821. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]
- Prepare human monoclonal antibodies from PBL of patients with high antibody titers against GD2 and/or GD3. These will be used to define the range or precise epitopes on these gangliosides recognized by the immune system and may have therapeutic value. [ Time Frame: to end of study ] [ Designated as safety issue: No ]
|Study Start Date:||December 2007|
|Study Completion Date:||November 2012|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Vaccine- KLH conjugates with GD2L and GD3L
Biological: KLH conjugates with GD2L and GD3L
6 vaccinations (on weeks 1, 2, 3, 8, 20 and 32) which will contain the same KLH conjugates with GD2L and GD3L. All vaccines contain KLH conjugates containing 30mcg of GD2L and 30mcg of GD3L and QS-DG or OPT-821. The initial 8 patients will receive the same QS-DG or OPT-821 vaccine dose in all of their vaccines. This dose will be 50 mcg for the first patient, 75 mcg for the second patient and 100 mcg for the third through eighth patients. In all subsequent patients the 1st, 4th and 5th vaccinations will include 150 mcg of OPT-821. The 2nd and 3rd vaccinations will contain 100 mcg of OPT-821 and the 6th vaccination will contain 200 mcg of OPT-821.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00597272
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Paul Chapman, MD||Memorial Sloan Kettering Cancer Center|