- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT00091143
Fludarabine Followed by Vaccine Therapy and White Blood Cell Infusions in Treating Patients With Unresectable or Metastatic Melanoma
A Pilot Trial of Therapeutic Vaccination With a Modified gp100 Melanoma Peptide (gp100:209-217(210M)), Montanide ISA 51, and KLH With Reconstitution After Chemotherapy to Induce Lymphopenia in Patients With Metastatic Melanoma
RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Vaccines made from peptides may make the body build an immune response to kill tumor cells. Infusions of a person's white blood cells may be able to replace immune cells that were destroyed by chemotherapy. Combining fludarabine with vaccine therapy and white blood cell infusions may kill more tumor cells.
PURPOSE: This randomized phase I trial is studying the side effects of giving vaccine therapy together with fludarabine and white blood cell infusions and to see how well it works in treating patients with unresectable or metastatic melanoma.
Visão geral do estudo
Status
Condições
Descrição detalhada
OBJECTIVES:
Primary
- Determine the toxicity and immune effects of vaccination comprising modified gp100 peptide (gp100:209-217[210M]), Montanide ISA-51, and keyhole limpet hemocyanin followed by peripheral blood mononuclear cell reinfusion after treatment-induced lymphopenia with fludarabine in patients with unresectable or metastatic melanoma.
- Determine the induction of antigen-specific T-cell responses in patients treated with this regimen.
- Determine the kinetics and duration of immune response in patients treated with this regimen.
- Compare the immunologic effects of this regimen in these patients with historical results.
Secondary
- Compare 2 different dosing schedules of fludarabine, in terms of induction of lymphopenia and granulocytopenia and on the induction of a specific immune response to this vaccine, in these patients.
OUTLINE: This is a pilot, randomized study. Patients are randomized to 1 of 2 treatment arms.
Within 2 weeks before the start of fludarabine, all patients undergo leukapheresis over 4-6 hours for the collection of peripheral blood mononuclear cells (PBMCs).
- Arm I: Patients receive fludarabine IV over 30 minutes on days 1-5.
- Arm II: Patients receive fludarabine as in arm I on days 1, 3, and 5. In both arms, patients receive autologous PBMCs IV over approximately 30 minutes on day 8 and vaccination comprising gp100:209-217(210M) peptide, Montanide ISA-51, and keyhole limpet hemocyanin subcutaneously on days 8, 22, 36, 50, and 64. Patients with stable or responding disease continue to receive vaccination on day 78 and then every 28-31 days for up to 1 year.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 20 patients (10 per treatment arm) will be accrued for this study within 2 years.
Tipo de estudo
Inscrição (Antecipado)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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Oregon
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Portland, Oregon, Estados Unidos, 97213-2967
- Providence Cancer Center at Providence Portland Medical Center
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed malignant melanoma
- Metastatic or unresectable disease
- Measurable disease
- HLA-A2 positive
- Received at least 1 prior immunotherapy and/or chemotherapy regimen for metastatic disease (first 6 patients only)
- No known brain metastases unless previously treated with radiotherapy and/or surgery AND is stable for at least 1 month after treatment
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2 OR
- Karnofsky 60-100%
Life expectancy
- More than 3 months
Hematopoietic
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Absolute lymphocyte count ≥ 500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10 g/dL (transfusions allowed)
- Hematocrit ≥ 24%
- No other active bleeding
Hepatic
- Bilirubin < 2 times upper limit of normal (ULN) (unless due to Gilbert's disease)
- AST and ALT < 3 times ULN
- Hepatitis B surface antigen negative
- Hepatitis C antibody negative
Renal
- Creatinine < 2 mg/dL
- No uncontrolled hypercalcemia
Cardiovascular
- No uncontrolled symptomatic congestive heart failure
- No unstable angina pectoris
- No uncontrolled cardiac arrhythmia
- No uncontrolled hypertension
Pulmonary
- No uncontrolled bronchospasm
- No hemoptysis
Immunologic
Negative serology for all of the following:
- HIV-1 and HIV-2
- HTLV-1 and -2
- Syphilis
- Rheumatoid factor < 43 units/μL
- Anti-nuclear antibody < 11 units/μL
- No history of multiple sclerosis, systemic lupus erythematosus, or myasthenia gravis
- No primary or secondary immunodeficiency
- No active infection
- No allergy to seafood or shellfish that would preclude study participation
Other
- No active gastrointestinal bleeding
- No uncontrolled hyperglycemia
- No other medical or psychiatric condition or social situation that would preclude study compliance
- No other uncontrolled illness
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3-4 months after study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- No prior immunization with gp100:209-217(210M) peptide
Chemotherapy
- See Disease Characteristics
- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
Endocrine therapy
- More than 2 weeks since prior steroid therapy except replacement steroids or inhaled steroids
- No concurrent corticosteroids except replacement steroids
- No concurrent dexamethasone
Radiotherapy
- See Disease Characteristics
- More than 2 weeks since prior radiotherapy
Surgery
- See Disease Characteristics
- Recovered from prior surgery
Other
- No other concurrent investigational agents
- No other concurrent anticancer therapy
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
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Toxicity by clinical and laboratory observation at 1 month
|
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Antigen-specific T-cell responses by tetramer analysis, ELISPOT, and cytokine flow cytometry periodically
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Medidas de resultados secundários
Medida de resultado |
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Compare 2 different dosing schedules of fludarabine in terms of lymphocyte recovery using a complete blood count periodically
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Tumor regression by standard imaging at study completion
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Colaboradores e Investigadores
Colaboradores
Investigadores
- Investigador principal: Walter J. Urba, MD, PhD, Providence Cancer Center, Earle A. Chiles Research Institute
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Neoplasias por Tipo Histológico
- Neoplasias
- Tumores Neuroectodérmicos
- Neoplasias, Células Germinativas e Embrionárias
- Neoplasias, Tecido Nervoso
- Tumores Neuroendócrinos
- Nevos e Melanomas
- Melanoma
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Antimetabólitos, Antineoplásicos
- Antimetabólitos
- Agentes Antineoplásicos
- Agentes imunossupressores
- Fatores imunológicos
- Adjuvantes Imunológicos
- Fludarabina
- Fosfato de fludarabina
- Adjuvante de Freund
- Hemocianina de lapa
Outros números de identificação do estudo
- CDR0000383908
- PPMC-IRB-02-99
- NCI-6361
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