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

Melanoma (Skin) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00295958
• Other study ID #: 060041
• Secondary ID: 06-C-0041NCI-754
• Status: Completed
• Phase: Phase 2
• First received: February 23, 2006
• Last updated: June 12, 2012
• Start date: December 2005
• Est. completion date: July 2008

Study information

• Verified date: June 2012
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00263510

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: July 2008
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)
• Non-melanomatous Skin Cancer
• Skin Neoplasms

Intervention

Biological:
• LMB-2 immunotoxin

• MART-1 antigen

• gp100 antigen

• incomplete Freund's adjuvant

Locations

Country	Name	City	State
United States	NCI - Surgery Branch	Bethesda	Maryland
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
National Institutes of Health Clinical Center (CC)	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective clinical response rate			No
Secondary	Changes in levels of CD4+, CD25+ regulatory T cells			No
Secondary	Ability of LMB-2 to augment peptide vaccination			No
Secondary	Toxicity			Yes