Clinical trial NCT00295958: LMB-2 Immunotoxin and Vaccine Therapy in Treating Patients With Metastatic Melanoma That Cannot Be Removed By Surgery
Official title: Phase II Evaluation of Peptide Immunization and LMB-2 in Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma (Skin)
Non-melanomatous Skin Cancer
Keywords: recurrent melanoma
stage IV melanoma
skin cancer
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-02-24
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Objective clinical response rate
Secondary outcomes:
measure: Changes in levels of CD4+, CD25+ regulatory T cells
measure: Ability of LMB-2 to augment peptide vaccination
measure: Toxicity
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
state: Maryland
city: Bethesda
country: United States
facility: NCI - Surgery Branch
state: Maryland
Study officials:
affiliation: NCI - Surgery Branch
name: Steven A. Rosenberg, MD, PhD
role: STUDY_CHAIR
References: