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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00597272
First received: January 8, 2008
Last updated: November 19, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention
Melanoma
Biological: KLH conjugates with GD2L and GD3L

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 34
Study Start Date: December 2007
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 βHCG 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00597272

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Paul Chapman, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00597272     History of Changes
Other Study ID Numbers: 06-086
Study First Received: January 8, 2008
Last Updated: November 19, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
melanoma
resected local
systemic metastasis

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014