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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00597272
• Other study ID #: 06-086
• Status: Completed
• Phase: N/A
• First received: January 8, 2008
• Last updated: November 19, 2012
• Start date: December 2007
• Est. completion date: November 2012

Study information

• Verified date: November 2012
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• Patients =18 with AJCC stage III or IV melanoma two weeks to one year after becoming clinically free of disease will be eligible.

• For all patients' pathology slides must be reviewed by the Memorial Hospital Department of Pathology to confirm diagnosis of cutaneous melanoma.

• All patients must have a Karnofsky performance status of =80.

• Patients may have received previous radiation, chemotherapy or systemic immunotherapy (completed at least 4 weeks prior to vaccination).

• A CBC must be performed within 2 weeks prior to vaccination with the WBC > or equal to 3.0 cells/mm3, Platelets >100,000/mm3,

• A screening profile must be performed within 2 weeks prior to vaccination with the total bilirubin = 2.0, and other LFTs within normal limits for patient's age.

• Chest, abdomen and pelvic CT or MRI must be performed within 4 weeks of the initiation of treatment showing no evidence of disease.

• Women of child bearing potential and sexually active males must be counseled to use an accepted and effective method of contraception (including abstinence) while on treatment.

Exclusion Criteria:

• Patients previously treated with KLH or ganglioside containing vaccines, or monoclonal antibodies against gangliosides are not eligible.

• Women must not be pregnant (negative ßHCG within 2 weeks of vaccination if of childbearing potential).

• Patients with other active cancers within the past 2 years, (excluding basal cell, squamous carcinomas of the skin or cervical carcinoma-in-situ) are not eligible.

• Any medical condition which might make it difficult for the patient to complete the full course of treatments or to respond immunologically to them is grounds for exclusion, at the discretion of the Principal Investigator.

• Patients requiring anti-inflammatory medications such a steroids, NSAIDS or full dose aspirin are not eligible.

• There must be no evidence of metastatic disease at the time of the first vaccine. However, patients who develop new metastases during treatment may continue on treatment as long as no systemic treatment is indicated and any local treatment such as surgical resection or radiation would not cause a delay in vaccination or two weeks or more.

Study Design

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

Related Conditions & MeSH terms

• Melanoma

Intervention

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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		conclusion of study	Yes
Secondary	Evaluate the antibody response following vaccination with the bivalent vaccine plus QS-DG or OPT-821.		conclusion of study	No
Secondary	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.		to end of study	No

External Links

•   Memorial Sloan-Kettering Cancer Center