Interleukin-7 and Vaccine Therapy in Treating Patients With Metastatic Melanoma
Study Details
Study Description
Brief Summary
RATIONALE: Interleukin-7 may stimulate a person's white blood cells to kill tumor cells. Vaccines made from peptides may make the body build an immune response to kill tumor cells. Combining interleukin-7 with vaccine therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of interleukin-7 when given with vaccine therapy in treating patients with metastatic melanoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
OBJECTIVES:
Primary
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Determine the maximum tolerated dose of interleukin-7 (IL-7) when administered with melanoma peptide vaccine emulsified in Montanide ISA-51 in patients with metastatic melanoma.
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Determine the safety of this regimen in these patients.
Secondary
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Determine the biological effects of this regimen on T-cell function and phenotype at various doses and at the optimal biological dose in these patients.
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Determine the pharmacokinetic and pharmacodynamic characteristics of IL-7 in patients treated with this regimen.
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Determine the antitumor effects of IL-7, in terms of a dose-escalation strategy, in these patients.
OUTLINE: This is a dose-escalation study of interleukin-7 (IL-7).
Patients receive IL-7 subcutaneously (SC) on days 0, 3, 6, 9, 12, 15, 18, and 21. Patients also receive melanoma peptide vaccine comprising gp100 antigen and MART-1 antigen emulsified in Montanide ISA-51 SC on days 0, 7, 14, and 21 in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of IL-7 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After the MTD is determined, an additional 13 patients are treated at that dose level.
Patients are followed at 1, 2, and 5 weeks, at 3 and 6 months, and then at 1 year.
PROJECTED ACCRUAL: A total of 3-37 patients will be accrued for this study within 1-12.3 months.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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Histologically confirmed melanoma
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Metastatic disease
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Measurable or evaluable disease
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Disease progression during or after prior interleukin-2 (IL-2) OR ineligible to receive high-dose IL-2* OR has disease burden for which IL-2 is not indicated* NOTE: *If patient did not receive prior IL-2, must have progressed after prior standard first-line therapy (e.g., metastasectomy for single lesions or dacarbazine)
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HLA-A*0201-positive disease
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- At least 3 months
Hematopoietic
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Absolute neutrophil count > 1,000/mm^3*
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Absolute lymphocyte count ≥ 200/mm^3*
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Platelet count > 100,000/mm^3
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No proliferative hematologic disease NOTE: *For 2 consecutive readings performed on 2 different days
Hepatic
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AST and ALT < 3 times upper limit of normal (ULN)
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PT/PTT ≤ 1.5 times ULN
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Hepatitis B negative
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Positive hepatitis B serology indicative of prior immunization (i.e., positive for antibody against hepatitis B surface antigen AND negative for antibody against hepatitis B core antigen) allowed
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Hepatitis C negative
Renal
- Creatinine ≤ 1.4 mg/dL
Cardiovascular
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Ejection fraction > 45% by MUGA for patients ≥ 50 years of age OR with a history of cardiac disease
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No resting blood pressure > 140/90 mm Hg with standard antihypertensive therapy
Pulmonary
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DLCO/VA and FEV_1 > 50% of predicted on pulmonary function test for smokers OR for patients with clinical evidence of compromised pulmonary function
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No history of severe asthma
Immunologic
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HIV negative
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No history of autoimmune disease
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No splenomegaly
Other
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective contraception
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No other medical or psychiatric disease that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
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See Disease Characteristics
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More than 4 weeks since prior cytokines
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No prior allogeneic hematopoietic stem cell transplantation
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No concurrent growth factors
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No concurrent monoclonal antibodies
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No other concurrent immunotherapy
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No other concurrent cytokines
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No other concurrent biologic agents
Chemotherapy
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See Disease Characteristics
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No prior intensive myeloablative chemotherapy
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No concurrent chemotherapy
Endocrine therapy
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More than 2 weeks since prior systemic corticosteroids for more than 72 hours in duration
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No concurrent systemic steroids
Radiotherapy
- Not specified
Surgery
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See Disease Characteristics
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No prior splenectomy
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No prior solid organ transplantation
Other
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More than 4 weeks since prior cytotoxic therapy
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No other concurrent cytotoxic therapy
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No concurrent chronic anticoagulation therapy (e.g., high-dose warfarin, heparin, or aspirin)
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Concurrent low-dose warfarin (1-2 mg) allowed
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No concurrent chronic medication for asthma
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No concurrent immunosuppressive therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda | Maryland | United States | 20892-1182 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Steven A. Rosenberg, MD, PhD, NCI - Surgery Branch
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000387802
- NCI-04-C-0235
- NCT00088322