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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00295958
First received: February 23, 2006
Last updated: June 12, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Melanoma (Skin)
Non-melanomatous Skin Cancer
Biological: LMB-2 immunotoxin
Biological: MART-1 antigen
Biological: gp100 antigen
Biological: incomplete Freund's adjuvant
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Evaluation of Peptide Immunization and LMB-2 in Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Objective clinical response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in levels of CD4+, CD25+ regulatory T cells [ Designated as safety issue: No ]
  • Ability of LMB-2 to augment peptide vaccination [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Enrollment: 26
Study Start Date: December 2005
Study Completion Date: July 2008
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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
  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: NCT00295958

Locations
United States, Maryland
NCI - Surgery Branch
Bethesda, Maryland, United States, 20892-1201
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: Steven A. Rosenberg, MD, PhD NCI - Surgery Branch
  More Information

Additional Information:
No publications provided

Responsible Party: Steven A. Rosenberg, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00295958     History of Changes
Obsolete Identifiers: NCT00263510
Other Study ID Numbers: 060041, 06-C-0041, NCI-7542, NCI-P6702, CDR0000462165
Study First Received: February 23, 2006
Last Updated: June 12, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
recurrent melanoma
stage IV melanoma
skin cancer

Additional relevant MeSH terms:
Skin Neoplasms
Melanoma
Neoplasms by Site
Neoplasms
Skin Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Freund's Adjuvant
Immunotoxins
Antibodies, Monoclonal
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014