- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT00580060
Injection Of AJCC Stage IIB, IIC, III And IV Melanoma Patients With A Multi-Epitope Peptide Vaccine Using GM-CSF DNA As An Adjuvant: A Pilot Trial To Assess Safety And Immunity
Přehled studie
Postavení
Podmínky
Detailní popis
This is a pilot trial to investigate the use of GM-CSF DNA as an adjuvant for peptide vaccination in patients with metastatic melanoma. The objective of this study is to determine the safety and adjuvant effect of vaccination with the gene coding for human GM-CSF with a multi-epitope melanoma peptide vaccine (tyrosinase and gp100 peptides) in patients with AJCC stage IIB, IIC, III and IV melanoma who are HLA-A2+. We will assess whether use of GM-CSF DNA is safe and generates an immune response to peptides derived from antigens on melanoma cells.
In the Dose Ranging part of the study, cohorts of 3 patients will be treated at increasing dose levels of GM-CSF DNA delivered subcutaneously (100, 400, or 800 ug), followed by administration of both peptides subcutaneously to the same site on day 5 or day 6. Patients will be treated monthly for three immunizations. Pharmacokinetic studies will be performed during the first cycle. Patients' peripheral blood mononuclear cells will be collected in order to measure the T cell responses induced by the vaccines. Toxicity will be assessed during this part of the study, although we do not expect to achieve a dose limiting toxicity (DLT). The dose for the second part of the study will be the maximum tolerated dose.
The second part of the study will assess the immunological efficacy of the vaccine. Nine patients will receive GM-CSF DNA delivered subcutaneously at one site, followed by administration of both peptides to the same site on day 5 or day 6, every month for three immunizations. A total of at least 18 patients is planned for both phases of the study. Patients' peripheral blood mononuclear cells will be collected in order to measure the T cell responses induced by the vaccines. Specifically, Elispot assays for CD8+ T cells responses against the peptides will be assessed, and will be the primary method to determine the generation of a specific immune response to the peptide antigens.
Typ studie
Zápis (Aktuální)
Fáze
- Raná fáze 1
Kontakty a umístění
Studijní místa
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New York
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New York, New York, Spojené státy, 10065
- Memorial Sloan-Kettering Cancer Center
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dítě
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Patients must have documented malignant melanoma, American Joint Commission on Cancer (AJCC) stage IIB, IIC, III or IV (54). Patients with resectable stage IIB, IIC and III disease must have undergone surgical resection before participating in this study.
- Patients with choroidal melanoma may participate if they fulfill one of the following criteria: Basal diameter > or = 16 mm; Height > or = 8 mm or involvement of ciliary body with tumor.
- For all patients, pathology slides must be reviewed by the Pathology Department of Memorial Sloan-Kettering Cancer Center for confirmation of melanoma diagnosis.
- Patients must be HLA-A2 positive.
- Patients must weigh at least 25 kg to be eligible. Patients must be able to read the consent form and give informed consent. Parent or legal guardians of patients who are minors will sign the informed consent form.
- Patients must have a Karnofsky performance status of at least 80.
- LDH ≤ 2x upper limit of normal value; albumin ≥ 3.5 mg/dl. Creatinine ≤ 2mg/dl and AST ≤ 2- fold upper limit of normal.
- A CBC prior to vaccination with WBC ≥ 3000, platelets ≥ 100,000.
- A negative serum bHCG within 2 weeks of vaccination in women of childbearing age.
- Patients must be free of detectable brain metastases. (Brain MRI or CT pre-protocol)
Exclusion Criteria:
- Patients may not be receiving or have received chemotherapy, immunotherapy or radiation therapy within the previous 4 weeks or nitrosourea chemotherapy within the previous 6 weeks. Patients must be fully recovered from any previous therapy or surgery.
- Patients may not have been previously immunized with vaccines containing tyrosinase or gp100, or peptides derived from tyrosinase or gp100.
- Creatinine > 2mg/dl (or history of Creatinine > 2 mg/dl) and AST ≥ 2 fold upper limit of normal.
- Any medical condition or use of medication (e.g., active autoimmune disease, immunodeficiency or corticosteroids) which might make it difficult for the patient to complete the full course of treatments or to respond immunologically to vaccines is grounds for exclusion, at the discretion of the Principal Investigator or co-Principal Investigators. Patients may not have taken systemic corticosteroids (orally or intravenously) within the previous 6 weeks. Inhaled or nasal steroids are permitted.
- Patients who have preexisting retinal or choroidal eye disease (except as outlined in section 5.1.1) will be excluded.
- Patients with serious underlying medical conditions, active infections requiring antimicrobial drugs, or active bleeding will be ineligible.
- Pregnant women, women who are less than 3 months post-partum or women who are nursing are not eligible. Women of childbearing age and sexually active men must be using appropriate contraception during the course of this study and for 3 months following completion.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Časové okno |
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To establish the safety and a recommended dose of subcutaneous human GM-CSF DNA given in conjunction with a multi-epitope peptide vaccine in patients with AJCC stage IIB, IIC, III and IV melanoma who are HLA-A2+.
Časové okno: Up to 15 years post treatment,
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Up to 15 years post treatment,
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To evaluate serum pharmacokinetics of GM-CSF after subcutaneous administration of human GM-CSF DNA.
Časové okno: All patients entered in the Dose Ranging study will undergo pharmacokinetic studies during their first course of therapy.
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All patients entered in the Dose Ranging study will undergo pharmacokinetic studies during their first course of therapy.
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If toxicities are encountered in the dose ranging part of the study, to establish the maximum tolerated dose (MTD) and dose limiting toxicities (DLT).
Časové okno: If toxicities less than DLT are encountered, then patients will continue on the study at the assigned dose level.
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If toxicities less than DLT are encountered, then patients will continue on the study at the assigned dose level.
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In the immunological efficacy study, to evaluate the immunogenicity of a multi-epitope peptide vaccine.
Časové okno: Up to 15 years post treatment.
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Up to 15 years post treatment.
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Sekundární výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
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A secondary endpoint is to observe the patients for evidence of any anti-tumor response that is generated after vaccination.
Časové okno: Up to 15 years post treatment
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Up to 15 years post treatment
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Spolupracovníci a vyšetřovatelé
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Miguel-Angel Perales, MD, Memorial Sloan Kettering Cancer Center
Publikace a užitečné odkazy
Užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 00-142
- NCI Protocol #: 5906
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