LMB-2 Immunotoxin and Vaccine Therapy in Treating Patients With Metastatic Melanoma That Cannot Be Removed By Surgery
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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 |
- Objective clinical response rate [ Designated as safety issue: No ]
- 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) |
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 |
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| 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 | |
| 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 May 22, 2013