- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT00840931
Immunotherapy Using Lenalidomide + Bystander Vaccine in High Risk Myelodysplastic Syndrome (MDS)
10 de dezembro de 2019 atualizado por: H. Lee Moffitt Cancer Center and Research Institute
A Phase I Pilot Study of Immunotherapy Using Lenalidomide Plus "Bystander" Vaccine in Patients With High-Risk Myelodysplastic Syndrome (MDS)
The purpose of this study is to find out the maximum tolerated dose (MTD) of the combined therapy of lenalidomide (Revlimid®) and Granulocyte/macrophage colony stimulating factor and CD40 Ligand expressed in the K562 cell line (GM.CD40L) bystander vaccine.
This research is also being done to see how well the combination of these drugs works to fight myelodysplastic syndrome (MDS).
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
Fixed dose of lenalidomide at 10 mg/day, Days 1- 21 of 28 days of treatment cycle, and 4 dose escalations of GM.CD40L vaccine: 10 X 10^6 GM.CDL cells per vaccination; 30 X 10^6 GM.CDL cells per vaccination; 60 X 10^6 GM.CDL cells per vaccination; 120 X 10^6 GM.CDL cells per vaccination; Vaccination at 2-week intervals, on days 8 and 22, for a total of four 28-day cycles.
Tipo de estudo
Intervencional
Inscrição (Real)
22
Estágio
- Fase 1
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Florida
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Tampa, Florida, Estados Unidos, 33612
- H. Lee Moffitt Cancer Center & Research Institute
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Must understand and voluntarily sign an informed consent form
- Age ≥18 years at the time of signing the informed consent form
- Able to comply with the study visit schedule and assessments required by the protocol
- Documented diagnosis of MDS with subtypes of Refractory Anemia with Excess Blast 1 (RAEB-1) (myeloblast ≥5-9%) or Refractory Anemia with Excess Blast 2 (RAEB-2) (myeloblast ≥10-19%) or intermediate 2, Acute myelogenous leukemia with bone marrow myeloblast >30% and high risk defined by International Prognostic Scoring System (IPSS) scores or refractory anemia with excess blast in transformation (RAEB-t) (myeloblast ≥ 20-30%) as per French-American-British Classification System (FAB) criteria. Any single or combination of cytogenetic abnormalities is allowed.
- Study treatment can be offered as first line treatment as long as the available food and Drug Administration (FDA) approved treatment options are explained by the treating physician and the participant declines such options.
- Study treatment can be offered to patients who have failed, cannot tolerate or do not wish to continue other therapeutic agents for MDS.
- Prior chemotherapy is allowed but should be off chemotherapy of any kind for at last 4 weeks prior to initiation of study therapy.
- Must be able to provide adequate bone marrow (BM) aspirate and biopsy specimens for histopathological evaluation, cytogenetic analysis and tissue banking during the screening procedure.
- Platelet count must be > 20,000/ µl without platelet transfusion.
- Absolute neutrophil count (ANC) must be >500/ µl without myeloid growth factor support.
- Should not be receiving erythropoietin and/or myeloid growth factor for at least 14 days prior to initiation of study therapy.
- Should not have current diagnosis or prior history of any autoimmune or immune deficiency disorders including human immunodeficiency virus positive/acquired immunodeficiency syndrome (HIV+/AIDS).
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
- Both male and female and members of all races and ethnic groups are eligible for this study.
Exclusion Criteria:
- Prior therapy with lenalidomide.
- Proliferative chronic myelomonocytic leukemia (CMML with WBC≥12,000/µL in peripheral blood), confirmed by bone marrow biopsy.
- Acute myelogenous leukemia with bone marrow myeloblast ≥30%
- MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases are excluded.
Any of the following laboratory abnormalities:
- Serum creatinine > 1.5 x upper limit of normal (ULN)
- Serum aspartic transaminase (AST) or alanine transaminase (ALT) >2.0 x ULN
- Serum total bilirubin > 2.0 mg/dL (34 µmol/L)
- Prior ≥ grade-2 national Cancer Institute Common Toxicity Criteria (NCI CTC) allergic reaction to thalidomide.
- Prior desquamating (blistering) rash while taking thalidomide.
- Prior allergic reaction to vaccination of any sort.
- Participants with ≥ grade-2 neuropathy.
- Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding.
- Use of cytotoxic chemotherapeutic agents, growth factors, or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days of the start of drug treatment.
- Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix) unless the participant has been free of disease for ≥3 years.
- Any serious medical condition or psychiatric illness that will prevent the participant from signing the informed consent form or will place the participant at unacceptable risk if he/she participates in the study.
- Pregnant or nursing females.
- Use of corticosteroids greater than the equivalent of prednisone 10mg daily within 4 weeks of the first vaccination, and on-going need for corticosteroids greater than the equivalent of prednisone 10 mg daily
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Immunotherapy
Participants will take two 5 mg capsules of lenalidomide per day for 21 days followed by 7 days of rest.
This 28 day period is considered 1 cycle.
Participants will receive 4 treatment cycles with 28 days in each cycle.
Those participants showing a clinical response after 4 cycles of treatment may continue to receive lenalidomide as a single agent for additional cycles at the treating Physicians discretion.
During each 28 day cycle participants will also receive GM.CD40L bystander vaccination injections in 2-week intervals on days 8 and 22 for a total of 8 immunizations during the 4 cycle treatment period.
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Patients will take 10 mg capsules of lenalidomide per day for 21 days followed by 7 days of rest.
This 28 day period is considered 1 cycle.
Patients will receive 4 treatment cycles with 28 days in each cycle.
Outros nomes:
In addition to lenalidomide, during each 28 day cycle patients will also receive GM.CD40L bystander vaccination injections in 2-week intervals on days 8 and 22 for a total of 8 immunizations during the 4 cycle treatment period.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Maximum Tolerated Dose (MTD)
Prazo: 24 months
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Determination of MTD of GM.CD40L bystander vaccine with lenalidomide in high-risk MDS patients.
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24 months
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Number of Participants with Toxicities
Prazo: 24 months
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Determination of toxicities associated with combination of GM.CD40L bystander vaccine with lenalidomide in high-risk MDS patients.
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24 months
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Number of Participants with Augmentation of Specific T Cell Immunological Functions
Prazo: 24 months
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Augmentation of specific T cell immunological functions; T cell proliferation and Interferon-γ production, delayed type hypersensitivity (DTH) sensitivity by lenalidomide.
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24 months
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Number of Participants with Reduction of Bone Marrow Myeloblast
Prazo: 24 months
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Reduction of bone marrow myeloblast from baseline to post treatment with lenalidomide and GM.CD40L bystander vaccine.
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24 months
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Number of Participants with Improvement of Hemoglobin and/or red blood cell (RBC) Transfusion Independence
Prazo: 24 months
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Improvement of hemoglobin and/or RBC transfusion independence after combined immunotherapy treatment.
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24 months
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Number of Participants with Resolution of Karyotypic Changes
Prazo: 24 months
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Resolution of karyotypic changes after combined treatment.
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24 months
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Number of Participants with Augmentation of Other T Cell Parameters
Prazo: 24 months
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Augmentation of other T cell parameters after the combined treatment.
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24 months
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Duration of Response
Prazo: 24 months
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Determination of response duration evaluated by Wilms Tumor 1 (WT1) expression and clinical outcomes.
Clinical response will be assessed using International Working Group (IWG) criteria.
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24 months
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Javier Pinilla, M.D., Ph.D., H. Lee Moffitt Cancer & Research Institute
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Links úteis
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
2 de fevereiro de 2009
Conclusão Primária (Real)
17 de fevereiro de 2014
Conclusão do estudo (Real)
1 de dezembro de 2019
Datas de inscrição no estudo
Enviado pela primeira vez
4 de fevereiro de 2009
Enviado pela primeira vez que atendeu aos critérios de CQ
10 de fevereiro de 2009
Primeira postagem (Estimativa)
11 de fevereiro de 2009
Atualizações de registro de estudo
Última Atualização Postada (Real)
11 de dezembro de 2019
Última atualização enviada que atendeu aos critérios de controle de qualidade
10 de dezembro de 2019
Última verificação
1 de dezembro de 2019
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Neoplasias
- Doenças da Medula Óssea
- Doenças Hematológicas
- Condições pré-cancerosas
- Síndromes Mielodisplásicas
- Pré-leucemia
- Efeitos Fisiológicos das Drogas
- Agentes Antineoplásicos
- Fatores imunológicos
- Inibidores de angiogênese
- Agentes Moduladores da Angiogênese
- Substâncias de crescimento
- Inibidores de crescimento
- Lenalidomida
Outros números de identificação do estudo
- MCC-14998
- 105861 (Outro identificador: USF IRB)
- RV-MDS-PI-202 (Outro identificador: Celgene Corp.)
- BB-IND 13478 (Outro identificador: CBER)
- 0803-907 (Outro identificador: OBA)
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .