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- Ensaio Clínico NCT00906334
Efficacy and Safety of ON 01910.Na in Myelodysplastic Syndrome (MDS) Patients With Trisomy 8 or Classified as Intermediate-1, -2 or High Risk
22 de junho de 2017 atualizado por: Onconova Therapeutics, Inc.
A Phase 2, Single-Arm Study To Assess The Efficacy and Safety Of 72-Hour Continuous Intravenous Dosing Of ON 01910.Na Administered Every Other Week in Myelodysplastic Syndrome Patients With Trisomy 8 or Classified as Intermediate-1, 2 or High Risk
This study will explore the efficacy and safety of a regimen of ON 01910.Na as a 48-hour continuous intravenous infusion once a week for 3 weeks of a 4-week cycle in MDS patients with Trisomy 8 or classified as Intermediate-1, -2 or High Risk who are not responding to current therapeutic options.
The rationale for this trial is based upon data from laboratory studies with ON 01910.Na and upon activity that has been observed in other clinical trials with ON 01910.Na in patients with MDS.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
This is a phase 2, study in which 14 MDS patients with Trisomy 8 or classified as Intermediate-1, -2 and High risk who meet all other inclusion/exclusion criteria will receive ON 01910.Na 800 mg/m^2/24h as an continuous intravenous infusion (CIV) over 48 hours once a week for 3 weeks of a 4-week cycle.
As of Amendment 3 to the Protocol, the regimen is changed to 1800 mg/24h for 72 hours every other week for the first four 2-week cycles and every 4 weeks afterwards.
The total study duration is 31 weeks, which includes a 2-week screening phase, a 27-week dosing phase, and a 4-week follow-up phase that begins after the last dose of ON 01910.Na.
Beginning at week 4, and every 2 weeks thereafter, patients will be assessed for response.
Patients who drop out for any reason will not be replaced.
Patients who achieve by week 29 a complete or partial response or stabilization of their disease are eligible to receive an additional 24 weeks of ON 01910.Na 1800 mg/24 h over 72 hours per week of a 4-week cycle.
Tipo de estudo
Intervencional
Inscrição (Real)
14
Estágio
- Fase 2
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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California
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Stanford, California, Estados Unidos, 94305
- Stanford Cancer Center
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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:
- Diagnosis of MDS confirmed within 2 weeks prior to study entry according to the World Health Organization (WHO) Criteria or the French-American-British (FAB) Classification.
- Trisomy 8 cytogenetics (simple or combined to other karyotypes) or patient classified as Intermediate-1 with bone marrow blasts equal to or greater than 5%, Intermediate-2 or High Risk MDS according to the IPSS score, or Patients with peripheral blood blasts equal to or greater than 5%.
- At least one cytopenia (Absolute Neutrophil Count < 1800/µl or Platelet Count <100,000/µl or Hemoglobin < 10 g/dL).
- Failure of, or insufficient response to Azacytidine or Decitabine administered for 4 to 6 cycles in patients classified as Intermediate-2 or High risk or to Erythrocyte stimulating agents (failure or insufficient response defined as transfusion dependence or Hemoglobin remaining below 10 g/dl) in Low or Intermediate-1 Risk Trisomy 8 patients.
- Failed to respond to, relapsed following, or opted not to participate in bone marrow transplantation.
- Off all other treatments for MDS (including filgrastim (G-CSF) and erythropoietin) for at least four weeks. As an exception, filgrastim (G-CSF) can be used before, during and after the protocol treatment for patients with documented febrile neutropenia (< 500/µl).
- ECOG Performance Status 0, 1 or 2.
- Willing to adhere to the prohibitions and restrictions specified in this protocol.
- Patient (or his/her legally authorized representative) must have signed an informed consent document indicating that he/she understands the purpose of and procedures required for the study and is willing to participate in the study.
Exclusion Criteria:
- Anemia due to factors other than MDS (including hemolysis or gastrointestinal bleeding).
- Hypoplastic MDS (cellularity <10%).
- Any active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast.
- History of HIV-1 seropositivity.
- Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
- Active infection not adequately responding to appropriate therapy.
- Total bilirubin > 1.5 mg/dL not related to hemolysis or Gilbert's disease, ALT or AST > 2 X ULN.
- Serum creatinine > 2.0 mg/dL or calculated creatinine clearance < 60 ml/min/1.73 m^2.
- Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <134 Meq/L).
- Women patients who are pregnant or lactating; Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol; Patients who do not agree to use adequate contraceptive [including prescription oral contraceptives (birth control pills), contraceptive injections, intrauterine device (IUD), double-barrier method (spermicidal jelly or foam with condoms or diaphragm), contraceptive patch, or surgical sterilization] before entry and throughout the study; Female patients with reproductive potential who do not have a negative serum beta-HCG pregnancy test at screening.
- Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.
- Uncontrolled hypertension (defined as a systolic pressure equal to or greater than 160 mmHg and/or a diastolic pressure equal to or greater than 110 mmHg).
- New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures
- Any concurrent investigational agent or chemotherapy, radiotherapy or immunotherapy.
- Treatment with standard MDS therapies or investigational therapy within 4 weeks of starting ON 01910.Na.
- Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements.
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: Não randomizado
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: 800 mg/m^2 ON 01910.Na
800 mg/m^2 ON 01910.Na administered as a continuous intravenous infusion (CIV) over 24 hours for 48 hours (i.e. 2 consecutive 24-hour infusions) every week for the first 3 weeks of 4-week cycle.
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The original dosing regimen was 800 mg/m^2 ON 01910.Na.
Outros nomes:
Per Amendment 3 to the Protocol, the dosing regimen was changed to 1800 mg ON 01910.Na.
Patients enrolled at the original dosing regimen could choose to remain in the original regimen or switch to the new regimen.
Outros nomes:
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Experimental: 1800 mg ON 01910.Na
1800 mg ON 01910.Na administered as a continuous intravenous infusion (CIV) over 24 hours for 72 hours (i.e., 3 consecutive 24-hour infusions) every 2 weeks for the first four 2-week cycles and every 4 weeks afterwards.
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The original dosing regimen was 800 mg/m^2 ON 01910.Na.
Outros nomes:
Per Amendment 3 to the Protocol, the dosing regimen was changed to 1800 mg ON 01910.Na.
Patients enrolled at the original dosing regimen could choose to remain in the original regimen or switch to the new regimen.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Overall Response Rate (ORR)
Prazo: 29 weeks
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The Overall Response Rate is defined as the proportion of patients who achieve a Complete Response, a Partial Response, A Complete Bone Marrow Response or a Hematologic Improvement (HI) according to the 2006 International Working Group (IWG) criteria.
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29 weeks
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Number of patients with adverse events
Prazo: From date of signing informed consent until 30 days after last dose of study drug up to 29 weeks
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The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 will be used to determine the grade of adverse events.
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From date of signing informed consent until 30 days after last dose of study drug up to 29 weeks
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Time to Overall Response
Prazo: 29 weeks
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Time to Overall Response is calculated from date of first study drug administration to date of first occurrence of any of the following responses: Complete Response (CR), Partial Response (PR), Marrow Complete Response (BMCR) or Hematologic Improvement (HI) as defined by the 2006 International Working Group (IWG) criteria.
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29 weeks
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Duration of Response
Prazo: 29 weeks
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Duration of response is calculated from date of first occurrence of any of the following responses: Complete Response (CR), Partial Response (PR), Marrow Complete Response (BMCR) or Hematologic Improvement (HI) as defined by the 2006 International Working Group (IWG) criteria) until the date of disease progression.
Patients who did not have disease progression are censored at the last bone marrow or bone marrow morphology assessment date.
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29 weeks
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Bone Marrow Complete Response
Prazo: Weeks 5, 13, 21 and 29
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The proportion of patients who achieve a Bone Marrow Complete Response (BMCR) according to 2006 International Working Group (IWG) criteria.
Bone marrow blasts are determined in bone marrow differential count.
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Weeks 5, 13, 21 and 29
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Cytogenetic Response
Prazo: 29 weeks
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Cytogenetic Response is defined as the number of patients who achieve a cytogenic response according to 2006 International Working Group criteria.
Complete response is defined as the disappearance of the chromosomal abnormality without appearance of new ones.
Partial response is defined as at least 50% reduction of the chromosomal abnormality.
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29 weeks
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Neutrophil Response
Prazo: 29 weeks
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The number of patients who achieve a Neutrophil Response according to 2006 International Working Group (IWG).
Neutrophil Response is defined as at least a 100% increase and an absolute increase greater than 0.5 x 10^9/L.
Pretreatment values must be less than 1.0 x 10^9/L.
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29 weeks
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Platelet Response
Prazo: 29 weeks
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The number of patients who achieve a Platelet Response according to 2006 International Working Group (IWG).
Platelet Response is defined as an absolute of greater than or equal to 30 x 10^9 for patients starting with less than 20 x 10^9/L.
increase and an absolute increase greater than 0.5 x 10^9/L.
Pretreatment values must be less than 1.0 x 10^9/L.
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29 weeks
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Erythroid Response
Prazo: 29 weeks
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The number of patients who achieve an Erythroid Response according to 2006 International Working Group (IWG).
Erythroid Response is defined as a Hgb increase equal to or greater than 1.5 g/dL and a relevant reduction of units of red blood cells (RBC) transfusions by an absolute number of at least 4 RBC transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 wells.
Only RBC transfusions given for a Hgb of 9.0 g/dL or lower pretreatment will count in the RBC transfusion response evaluation.
Pretreatment values of Hgb must be lower than 11 g/dL.
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29 weeks
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Time to Disease Progression
Prazo: 29 weeks
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Time to Disease Progression is calculated from date of first dose of study drug administration to date of disease progression recorded on the hematology response assessment clinical report form.
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29 weeks
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Time to Acute Myeloid Leukemia (AML) Progression
Prazo: 29 and 53 weeks
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Time to Acute Myeloid Leukemia (AML) Progression is calculated from date of first study drug administration to date of AML progression recorded on the Off Study Summary clinical report form.
Patients who do not have AML disease progression are censored at the last bone marrow or bone marrow morphology assessment date.
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29 and 53 weeks
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Overall Survival
Prazo: 29 and 53 weeks
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Overall Survival is calculated from date of first study drug administration to date of death.
In event of no death prior to study termination or data analysis cutoff, overall survival is censored at the last known date patient was alive
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29 and 53 weeks
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Proportion of patients who achieve a Complete Hematologic Response
Prazo: Up to 29 weeks
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The proportion of patients who achieve a Complete Remission (CR) Hematologic Response according to 2006 International Working Group (IWG) criteria.
Bone marrow blasts are determined in bone marrow differential count.
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Up to 29 weeks
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The proportion of patients who achieve a Partial Remission (CR)
Prazo: Up to 29 weeks
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The proportion of patients who achieve a Partial Remission (PR) Hematologic Response according to 2006 International Working Group (IWG) criteria.
Bone marrow blasts are determined in bone marrow differential count.
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Up to 29 weeks
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Investigador principal: Peter L. Greenberg, MD, Stanford University
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.
Publicações Gerais
- Garcia-Manero G, Fenaux P. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Blood Dec 2016, 128 (22) 2011; ASH 2016.
- Silverman LR, Greenberg P, Raza A, Olnes MJ, Holland JF, Reddy P, Maniar M, Wilhelm F. Clinical activity and safety of the dual pathway inhibitor rigosertib for higher risk myelodysplastic syndromes following DNA methyltransferase inhibitor therapy. Hematol Oncol. 2015 Jun;33(2):57-66. doi: 10.1002/hon.2137. Epub 2014 Apr 29.
- Navada SC, Silverman LR. The safety and efficacy of rigosertib in the treatment of myelodysplastic syndromes. Expert Rev Anticancer Ther. 2016 Aug;16(8):805-10. doi: 10.1080/14737140.2016.1209413. Epub 2016 Jul 15.
- Seetharam M, Fan AC, Tran M, Xu L, Renschler JP, Felsher DW, Sridhar K, Wilhelm F, Greenberg PL. Treatment of higher risk myelodysplastic syndrome patients unresponsive to hypomethylating agents with ON 01910.Na. Leuk Res. 2012 Jan;36(1):98-103. doi: 10.1016/j.leukres.2011.08.022. Epub 2011 Sep 14.
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
1 de maio de 2009
Conclusão Primária (Real)
1 de novembro de 2013
Conclusão do estudo (Real)
1 de novembro de 2013
Datas de inscrição no estudo
Enviado pela primeira vez
19 de maio de 2009
Enviado pela primeira vez que atendeu aos critérios de CQ
20 de maio de 2009
Primeira postagem (Estimativa)
21 de maio de 2009
Atualizações de registro de estudo
Última Atualização Postada (Real)
26 de junho de 2017
Última atualização enviada que atendeu aos critérios de controle de qualidade
22 de junho de 2017
Última verificação
1 de junho de 2017
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Processos Patológicos
- Neoplasias
- Doença
- Doenças da Medula Óssea
- Doenças Hematológicas
- Condições pré-cancerosas
- Aberrações cromossômicas
- Aneuploidia
- Duplicação cromossômica
- Síndrome
- Síndromes Mielodisplásicas
- Pré-leucemia
- Trissomia
- Efeitos Fisiológicos das Drogas
- Agentes Neurotransmissores
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Agentes Antineoplásicos
- Inibidores de proteína quinase
- Agentes de Glicina
- Glicina
- ON 01910
Outros números de identificação do estudo
- Onconova 04-17
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 .
Ensaios clínicos em ON 01910.Na
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Onconova Therapeutics, Inc.ConcluídoNeoplasias | Câncer | Câncer Avançado | Tumores SólidosEstados Unidos
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Onconova Therapeutics, Inc.ConcluídoNeoplasias | Câncer | Câncer Avançado | Tumores SólidosEstados Unidos
-
Onconova Therapeutics, Inc.ConcluídoCarcinoma Espinocelular de Cabeça e Pescoço | Carcinoma Espinocelular de Esôfago | Carcinoma Anal de Células Escamosas | Carcinoma Espinocelular Cervical | Carcinoma de células escamosas da pele | Carcinoma Espinocelular de Pulmão | Carcinoma Espinocelular PenianoEstados Unidos
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Onconova Therapeutics, Inc.The Leukemia and Lymphoma SocietyConcluídoSíndromes Mielodisplásicas | Leucemia Mielomonocítica Crônica | MDS | RAEBEstados Unidos, Bélgica, Alemanha, Espanha, França, Itália
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Onconova Therapeutics, Inc.RetiradoSíndrome mielodisplásicaEstados Unidos
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M.D. Anderson Cancer CenterOnconova Therapeutics, Inc.RescindidoLeucemia | Anemia | Mielofibrose | EsplenomegaliaEstados Unidos
-
Onconova Therapeutics, Inc.Concluído
-
Onconova Therapeutics, Inc.ConcluídoTumor SólidoEstados Unidos
-
Onconova Therapeutics, Inc.RetiradoSíndrome mielodisplásicaEstados Unidos
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National Heart, Lung, and Blood Institute (NHLBI)ConcluídoSíndrome Mielodisplásica (SMD)Estados Unidos