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

Phase II Evaluation of Peptide Immunization and LMB-2 in Metastatic Melanoma

RATIONALE: The LMB-2 immunotoxin can find tumor cells and kill them without harming normal cells. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving LMB-2 immunotoxin together with vaccine therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving LMB-2 immunotoxin together with vaccine therapy works in treating patients with metastatic melanoma that cannot be removed by surgery.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin); Non-melanomatous Skin Cancer
• Intervention / Treatment: Biological: gp100 antigen; Biological: incomplete Freund's adjuvant; Biological: MART-1 antigen; Biological: LMB-2 immunotoxin

Detailed Description

OBJECTIVES:

Primary

• 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

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

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.

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

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892-1182
      • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
    • Bethesda, Maryland, United States, 20892-1201
      • NCI - Surgery Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy more than 3 months
• WBC ≥ 3,000/mm^3
• Absolute lymphocyte count > 500/mm^3
• Platelet count ≥ 90,000/mm^3
• 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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Objective clinical response rate

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: February 23, 2006
• First Submitted That Met QC Criteria: February 23, 2006
• First Posted (Estimate): February 24, 2006

Study Record Updates

• Last Update Posted (Estimate): June 14, 2012
• Last Update Submitted That Met QC Criteria: June 12, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma; skin cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Skin Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Immunotoxins; Freund's Adjuvant
• Other Study ID Numbers: 060041; 06-C-0041; NCI-7542; NCI-P6702; CDR0000462165