Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia
21 de abril de 2016 atualizado por: Teva Branded Pharmaceutical Products R&D, Inc.
An Open-Label Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia
The primary objective of phase 1 of this study is to establish the recommended phase II dose (RP2D).
The primary objective of phase 2 of this study is to evaluate the safety and efficacy of bendamustine at the recommended pediatric dose for the treatment of pediatric patients with relapsed or refractory acute leukemia.
Visão geral do estudo
Tipo de estudo
Intervencional
Inscrição (Real)
43
Estágio
- Fase 2
- 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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Herston, Austrália
- Teva Investigational Site 300
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Parkville, Austrália
- Teva Investigational Site 301
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Randwick, Austrália
- Teva Investigational Site 302
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Minsk, Bielorrússia
- Teva Investigational Site 520
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Barretos-SP, Brasil
- Teva Investigational Site 615
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Caxias do Sul, Brasil
- Teva Investigational Site 616
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Curitiba-PR, Brasil
- Teva Investigational Site 613
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Porto Alegre, Brasil
- Teva Investigational Site 612
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Porto Alegre, Brasil
- Teva Investigational Site 614
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Sao Paulo, Brasil
- Teva Investigational Site 610
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Sao Paulo, Brasil
- Teva Investigational Site 611
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Sao Paulo-SP, Brasil
- Teva Investigational Site 617
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Toronto, Canadá
- Teva Investigational Site 100
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Singapore, Cingapura
- Teva Investigational Site 320
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California
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Orange, California, Estados Unidos
- Teva Investigational Site 17
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San Diego, California, Estados Unidos
- Teva Investigational Site 12
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Florida
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St. Petersburg, Florida, Estados Unidos
- Teva Investigational Site 10
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Maryland
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Baltimore, Maryland, Estados Unidos
- Teva Investigational Site 8
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Massachusetts
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Boston, Massachusetts, Estados Unidos
- Teva Investigational Site 16
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Michigan
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Detroit, Michigan, Estados Unidos
- Teva Investigational Site 9
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Mississippi
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Jackson, Mississippi, Estados Unidos
- Teva Investigational Site 1
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Missouri
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Kansas City, Missouri, Estados Unidos
- Teva Investigational Site 5
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St. Louis, Missouri, Estados Unidos
- Teva Investigational Site 14
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New York
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New York, New York, Estados Unidos
- Teva Investigational Site 15
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Oregon
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Portland, Oregon, Estados Unidos
- Teva Investigational Site 18
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Pennsylvania
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Hershey, Pennsylvania, Estados Unidos
- Teva Investigational Site 11
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Philadelphia, Pennsylvania, Estados Unidos
- Teva Investigational Site 7
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Tennessee
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Memphis, Tennessee, Estados Unidos
- Teva Investigational Site 19
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Texas
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Dallas, Texas, Estados Unidos
- Teva Investigational Site 3
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Fort Worth, Texas, Estados Unidos
- Teva Investigational Site 4
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Houston, Texas, Estados Unidos
- Teva Investigational Site 13
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Washington
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Seattle, Washington, Estados Unidos
- Teva Investigational Site 2
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Wisconsin
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Milwaukee, Wisconsin, Estados Unidos
- Teva Investigational Site 6
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Moscow, Federação Russa
- Teva Investigational Site 511
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St. Petersburg, Federação Russa
- Teva Investigational Site 510
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Jerusalem, Israel
- Teva Investigational Site 501
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Petach Tikva, Israel
- Teva Investigational Site 503
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Ramat Gan, Israel
- Teva Investigational Site 502
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Guadalajara, México
- Teva Investigational Site 603
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Mexico City, México
- Teva Investigational Site 600
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Mexico City, México
- Teva Investigational Site 601
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Monterrey, México
- Teva Investigational Site 602
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Auckland, Nova Zelândia
- Teva Investigational Site 303
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Bialystok, Polônia
- Teva Investigational Site 531
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Lublin, Polônia
- Teva Investigational Site 530
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Warszawa, Polônia
- Teva Investigational Site 532
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Seoul, Republica da Coréia
- Teva Investigational Site 330
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Seoul, Republica da Coréia
- Teva Investigational Site 331
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Seoul, Republica da Coréia
- Teva Investigational Site 332
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Seoul, Republica da Coréia
- Teva Investigational Site 333
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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
1 ano a 20 anos (Filho, Adulto)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Key Inclusion Criteria:
- The patient has histologically proven acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) that has relapsed or is refractory to the last regimen, and the patient is without alternative curative therapy.
- The patient's last myelosuppression therapy ended at least 2 weeks before the first dose of study drug.
- Nonhematologic acute toxic effects of prior therapy have resolved to grade 2 or less according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
- The patient has adequate liver function with bilirubin values less than or equal to 1.5 times the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values less than or equal to 5 times the age-appropriate ULN.
- The patient has adequate renal function with serum creatinine values less than 2 times ULN.
- The patient has Karnofsky or Lansky performance status of 60 or greater. Patients older than 16 years of age will be scored according to the Karnofsky scale and patients 16 years of age or younger will be scored according to the Lansky scale.
- The patient may have had hematopoietic stem cell transplantation.
- Women of childbearing potential (not surgically sterile) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of treatment and for 30 days after the end of treatment.
- Men not surgically sterile or who are capable of producing offspring must practice abstinence or use a barrier method of birth control, and must agree to continue use of this method for the duration of treatment and for 30 days after the end of treatment.
- The patient must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period, and willing to return to the clinic for the follow-up evaluation as specified in this protocol.
Key Exclusion Criteria:
- The patient has any active, uncontrolled systemic infection, severe concurrent disease, or symptomatic untreated central nervous system (CNS) involvement.
- The patient has evidence of active graft versus host disease.
- The patient has a known human immunodeficiency virus (HIV) infection.
- The patient has active hepatitis B or hepatitis C infection.
- The patient is a pregnant or lactating woman. Any women becoming pregnant during the study will be withdrawn from the study immediately.
- The patient has any serious uncontrolled medical or psychological disorder that would impair the ability of the patient to receive study drug.
- The patient has any condition that places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data.
- The patient has received any other investigational agent within 30 days of study entry.
- The patient has known hypersensitivity to bendamustine or mannitol.
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: Bendamustine
Bendamustine 90 or 120 mg/m^2 administered as an intravenous (IV) infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (maximum of 12 total cycles), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
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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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Recommended Phase II Dose (RP2D) of Bendamustine
Prazo: Induction Cycle (21- to 35-day cycle)
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RP2D was determined by a traditional 3+3 dose escalation design, with the following restrictions: only doses of 60, 90, 120, and 150 mg/m^2 were explored, and escalation to 150 mg/m^2 would only occur if the 120 mg/m^2 dose was deemed safe and pharmacokinetic data indicate subtherapeutic exposure as compared with adults.
The first cohort was administered bendamustine at the 90 mg/m^2 dose; de-escalation to the 60 mg/m^2 dose would only occur if the starting dose led to dose-limiting toxicity (DLT) in 2 or more participants.
A DLT was defined as any study drug-related nonhematologic adverse event (AE) that was grade 4 for toxicity by National Cancer Institute's Common Toxicity Criteria for AEs, version 4. In addition, grade 3 or above allergic reaction or skin rash were considered DLTs.
Hematologic AEs were not considered DLTs.
The dose level at which at least 2 of 3 or 2 of 6 participants had a DLT was considered as exceeding the RP2D.
The RP2D was the dose 1 step below that level.
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Induction Cycle (21- to 35-day cycle)
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Overall Response Rate (ORR)
Prazo: Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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ORR was calculated as follows: number of participants in the primary analysis set achieving a best overall response of complete remission without platelet recovery (CRp) or complete remission (CR), divided by the number of participants in the primary analysis set.
The most positive response for each patient during the study was counted.
The 95% CI was calculated using binomial parameter exact method.
Response was determined by the investigator, and evaluated per Jeha et al, 2006: A CR required no evidence of circulating blasts or extramedullary disease, an M1 marrow (≤ 5% bone marrow blasts), and recovery of peripheral counts (platelets ≥ 100 × 10^9/L and absolute neutrophil count ≥ 1.0 × 10^9/L).
A CR without platelet recovery (CRp) required all of the criteria for a CR with the exception of platelet recovery.
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Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Best Overall Tumor Response Rate
Prazo: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Biological activity of bendamustine was defined as achieving a best response of partial response (PR), CRp, or CR.
Rate was calculated as follows: number of participants in the primary analysis set achieving a best overall response of PR, CRp, or CR, divided by the number of participants in the primary analysis set.
The most positive response for each patient during the study was counted.
The 95% CI was calculated using binomial parameter exact method.
Response was determined by the investigator, and evaluated per Jeha et al, 2006: A PR had to meet the following criteria: complete disappearance of circulating blasts and an M2 marrow (≥ 5% and ≤ 25% bone marrow blasts) and appearance of normal progenitor cells or an M1 marrow that did not qualify for CR or CRp.
See Outcome Measure 2 for full definitions for CRp and CR.
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At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Best Overall Tumor Response Rate, by Phase
Prazo: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Biological activity of bendamustine was defined as achieving a best response of partial response (PR), CRp, or CR.
Rate was calculated as follows: number of participants in the primary analysis set achieving a best overall response of PR, CRp, or CR, divided by the number of participants in the primary analysis set.
The most positive response for each patient during the study was counted.
The 95% CI was calculated using binomial parameter exact method.
Response was determined by the investigator, and evaluated per Jeha et al, 2006: A PR had to meet the following criteria: complete disappearance of circulating blasts and an M2 marrow (≥ 5% and ≤ 25% bone marrow blasts) and appearance of normal progenitor cells or an M1 marrow that did not qualify for CR or CRp.
See Outcome Measure 2 for full definitions for CRp and CR.
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At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Duration of Response (DOR)
Prazo: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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DOR was determined for the participants with CR or CRp in the primary analysis set, defined as the time from first achieving remission to the time when progression was diagnosed, the participant died, or the participant started receiving new antineoplastic therapy.
Data from participants who do not progress were censored at the last valid assessments.
Median DOR and its 95% confidence interval was determined based on the Kaplan-Meier method.
Data from participants who received a transplant were censored at the time of the transplant.
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At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Maximum Observed Plasma Drug Concentration (Cmax) for Bendamustine and Its Metabolites (M3 and M4)
Prazo: Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Time to Maximum Plasma Drug Concentration (Tmax) for Bendamustine and Its Metabolites (M3 and M4)
Prazo: Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Area Under the Plasma Drug Concentration by Time Curve From Time 0 Until the Last Measurable Plasma Concentration (AUC0-t) for Bendamustine and Its Metabolites (M3 and M4)
Prazo: Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Area Under the Plasma Drug Concentration by Time Curve From Time 0 Until 24 Hours After Study Drug Administration (AUC0-24) for Bendamustine and Its Metabolites (M3 and M4)
Prazo: Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Publicações e links úteis
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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 agosto de 2010
Conclusão Primária (Real)
1 de agosto de 2011
Conclusão do estudo (Real)
1 de agosto de 2011
Datas de inscrição no estudo
Enviado pela primeira vez
16 de março de 2010
Enviado pela primeira vez que atendeu aos critérios de CQ
16 de março de 2010
Primeira postagem (Estimativa)
18 de março de 2010
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
23 de maio de 2016
Última atualização enviada que atendeu aos critérios de controle de qualidade
21 de abril de 2016
Última verificação
1 de abril de 2016
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- C18083/2046
- 2010-020768-40 (Número EudraCT)
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 .