Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

LMB-2 Immunotoxin and Vaccine Therapy in Treating Patients With Metastatic Melanoma That Cannot Be Removed By Surgery

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI NCI-06-C-0041 7542, NCI-7542, NCI-P6702, NCT00295958

Objectives

Primary

1. Determine objective clinical response in patients with progressive, unresectable metastatic melanoma treated with recombinant LMB-2 immunotoxin and peptide vaccination comprising gp100:209-217 (210M) antigen, MART-1:27-35 antigen, and Montanide ISA-51.

Secondary

1. Determine changes in levels of CD4+, CD25+ regulatory T cells in peripheral blood before and after treatment in patients treated with this regimen.
2. Determine the ability of recombinant immunotoxin LMB-2 to augment peptide vaccination in these patients.
3. Determine the toxicity profile of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Diagnosis of metastatic melanoma
  • Unresectable disease
  • Progressive disease while receiving standard therapy (e.g., interleukin-2 or dacarbazine)



• HLA-A0201 positive



• Measurable disease



• The following are not allowed:
  • Resectable local/regional disease
  • Patients whose serum neutralizes LMB-2 in tissue culture, due either to antitoxin or antimouse-immunoglobulin G antibodies (> 75% of the activity of 1 ug/mL of LMB-2)
  • Received LMB-2 on another trial

Prior/Concurrent Therapy:

• See Disease Characteristics
• More than 12 weeks since prior monoclonal antibody therapy
• More than 3 weeks since prior and no concurrent systemic therapy for cancer
• No concurrent chronic anticoagulant therapy
• No concurrent systemic steroid therapy

Patient Characteristics:

• ECOG performance status 0-2
• Life expectancy more than 3 months
• WBC ≥ 3,000/mm³
• Absolute lymphocyte count > 500/mm³
• Platelet count ≥ 90,000/mm³
• Bilirubin ≤ 2.0 mg/dL (≤ 3.0 mg/dL for patients with Gilbert's syndrome)
• AST and ALT ≤ 2.5 times normal
• Albumin ≥ 3.0 g/dL
• No hepatitis B surface antigen or hepatitis C positivity
• Creatinine ≤ 1.4 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing or active infection
• Ejection fraction ≥ 45% by echocardiogram or thallium stress test (for patients > 50 years of age OR who have a history of cardiovascular disease)
• LVEF ≥ 45%
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No known HIV positivity
• No autoimmune disease
• No immunodeficiency
• No other malignancies
• Must be willing to undergo leukapheresis

Expected Enrollment

A total of 26 patients will be accrued for this study.

Outcomes

Objective clinical response rate

Changes in levels of CD4+, CD25+ regulatory T cells
Ability of LMB-2 to augment peptide vaccination
Toxicity

Outline

Patients receive LMB-2 immunotoxin IV over 30 minutes twice on days 1-3. Patients then receive peptide vaccinations comprising gp100:209-217 (210M) antigen emulsified in Montanide ISA-51 subcutaneously (SC), and MART-1:27-35 vaccine emulsified in Montanide ISA-51 SC on days 4, 5, 6, and 24-27 (course 1). After week 8, patients achieving tumor response may receive 1 additional course in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically in the absence of disease progression.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Steven Rosenberg, MD, PhD, Protocol chair		Ph: 866-820-4505 Email: sar@nih.gov

Registry Information
Official Title		Phase II Evaluation of Peptide Immunization and LMB-2 in Metastatic Melanoma
Trial Start Date		2005-12-07
Trial Completion Date		2008-04-22
Registered in ClinicalTrials.gov		NCT00295958
Date Submitted to PDQ		2005-12-01
Information Last Verified		2007-10-04