Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI E-2696 E2696

Objectives

I.  Determine the effect of high-dose interferon alfa (IFN-A) on anti-GM2 
antibody response when administered during or after vaccination with GM-2 
ganglioside covalently conjugated to keyhole limpet hemocyanin (KLH) plus the 
immunologic adjuvant QS21 (GM2-KLH/QS21) in patients with resected melanoma at 
high risk of recurrence.

II.  Assess the toxic effects of GM2-KLH/QS21 when administered with high-dose 
IFN-A.

Entry Criteria

Disease Characteristics:

Histologically confirmed malignant melanoma in 1 of the following categories:
  Newly diagnosed primary stage II disease that is greater than 4 mm deep
  Stage III/IV disease
    Skin or subcutaneous lesions beyond site of drainage (M1a)
    Solitary resectable meastases involving visceral organs (M1b) and now      
     disease free
  First clinically detected nodal recurrence

Entry required within 365 days of complete resection rendering patient
clinically free of disease
  Negative abdominothoracic CT required of patients with M1 disease

Patient must be ineligible for protocol E-1694

Prior/Concurrent Therapy:

Recovered from all prior therapy

Biologic therapy:
  No prior immunotherapy, e.g.:
     Tumor vaccines       Interferons
     Interleukins         Levamisole
     Other biological response modifiers

Chemotherapy:
  No prior chemotherapy (including infusion or perfusion therapy)

Endocrine therapy:
  No prior hormonal therapy

Radiotherapy:
  No prior radiotherapy to intact lymph node basins

Surgery:
  See Disease Characteristics

Other:
  At least 2 weeks since systemic anti-inflammatory drugs, antihistamines, or
   corticosteroids and not expected to require such therapy

Patient Characteristics:

Age:
  18 and over

Performance status:
  ECOG 0 or 1

Hematopoietic:
  WBC at least 4,000/mm3
  Platelet count at least 100,000/mm3

Hepatic:
  Bilirubin no greater than twice normal
  AST no greater than twice normal
  Alkaline phosphatase and LDH normal (negative contrast-enhanced liver CT or
     MRI required if elevated)

Renal:
  Creatinine no greater than 1.8 mg/dL

Cardiovascular:
  No cardiac arrhythmias requiring therapy
  No history of congestive heart failure 
  No history of ischemic heart disease (NYHA class III/IV status)

Other:
  No active infection requiring antimicrobial drugs
  No active bleeding
  No severe allergy to shellfish
  No autoimmune disorder or immunosuppressive condition, including splenectomy
  No organic brain syndrome or significant impairment of basal cognitive
     function
  No CNS-demyelinating, inflammatory disease, or hereditary or acquired
     peripheral neuropathy
  No psychiatric or medical condition contraindicating protocol participation
  No second malignancy within 5 years except:
     Nonmelanomatous skin cancer
     In situ lobular carcinoma of the breast
     In situ cervical carcinoma
     Atypical melanocytic hyperplasia or Clark I melanoma in situ
  No pregnant or nursing women
     Negative pregnancy test required within 2 weeks prior to entry
  Effective contraception required of fertile patients throughout study and
     for 18 months thereafter

Expected Enrollment

A total of 140 patients will be accrued over 1-1.2 years.

Outcomes

Effect of high-dose IFN-A on anti-GM2 antibody response
Toxicity

Outline

Randomized study.  The following acronyms are used:
  GM2-KLH     Ganglioside GM-2 conjugated to Keyhole Limpet Hemocyanin
  IFN-A       Interferon alfa (Schering), NSC-377523
  QS21        Immunologic Adjuvant QS21, NSC-679689

Arm I:  Biological Response Modifier Therapy.  GM2-KLH/QS21; with IFN-A 
(beginning with vaccine therapy).

Arm II:  Biological Response Modifier Therapy.  GM2-KLH/QS21; with IFN-A 
(beginning after vaccine therapy).

Arm III:  Vaccine Therapy.  GM2-KLH/QS21.

Stuckert JJ, Tarhini AA, Lee S, et al.: Interferon alfa-induced autoimmunity and serum S100 levels as predictive and prognostic biomarkers in high-risk melanoma in the ECOG-intergroup phase II trial E2696. [Abstract] J Clin Oncol 25 (Suppl 18): A-8506, 473s, 2007.

Stuckert JJ II, Tarhini A, Lee S, et al.: Interferon alfa-induced autoimmunity in patients with high-risk melanoma participating in ECOG phase II trial E2696. [Abstract] American Association for Cancer Research: 98th Annual Meeting, April 14-18, 2007, Los Angeles, CA. A-166, 2007.

Tarhini AA, Stuckert J, Lee S, et al.: Prognostic significance of serial serum S100 protein levels in high-risk surgically resected melanoma in ECOG phase II trial E2696. [Abstract] American Association for Cancer Research: 98th Annual Meeting, April 14-18, 2007, Los Angeles, CA. A-2437, 2007.

Kirkwood JM, Ibrahim J, Lawson DH, et al.: High-dose interferon alfa-2b does not diminish antibody response to GM2 vaccination in patients with resected melanoma: results of the Multicenter Eastern Cooperative Oncology Group Phase II Trial E2696. J Clin Oncol 19 (5): 1430-6, 2001.[PUBMED Abstract]

Chapman P, Morrissey D, Ibrahim J, et al.: Eastern Cooperative Oncology Group phase II randomized adjuvant trial of GM2-KHL+(GMK) vaccine plus/minus high dose interferon-a2b (HD IFN) in melanoma (MEL). [Abstract] Proceedings of the American Society of Clinical Oncology 18: A2078, 538a, 1999.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

John Kirkwood, MD, Protocol chair		Ph: 412-692-4724