Last updated on November 2016

Study With Azacitidine in Pediatric Subjects With Newly Diagnosed Advanced Myelodysplastic Syndrome (MDS) and Juvenile Myelomonocytic Leukemia (JMML)


Brief description of study

Indication Treatment of pediatric subjects with newly diagnosed advanced myelodysplastic syndrome (MDS) or juvenile myelomonocytic leukemia (JMML) prior to hematopoietic stem cell transplantation (HSCT). Objectives Primary Objective The primary objective is to assess the treatment effect on response rate (MDS: either complete remission [CR], partial remission [PR], or marrow CR; JMML: either clinical complete remission [cCR] or clinical partial remission [cPR]); at Cycle 3 Day 28 (each cycle is 28 days) and to compare against standard therapy using a matched-pairs analysis of historical data. Secondary Objective The secondary objective is to further evaluate safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of azacitidine in this subject population. Study Design This is a prospective, open-label, Phase 2 study consisting of 2 parallel experimental arms, one for each disease group: MDS and JMML. Each arm is designed based on Simon's Optimal 2 stage study design. The sample size has been calculated to allow evaluation of the response rate at 28 day-Cycle 3 Day 28 in each of the 2 disease groups. Each of the experimental arms will also individually be compared against a historical control arm using data retrospectively collected from the European Working Group of MDS in childhood (EWOG-MDS) registry by means of a matched-pairs analysis; matched for predefined subject baseline characteristics defined before any results from this study are known post Stage 1. Twenty subjects with MDS and 35 JMML subjects evaluable for the primary endpoint (ie, subjects that receive at least 1 dose of investigational product [IP]) will be enrolled at approximately 45 centers in Europe. Each experimental arm has 1 interim analysis planned (at the end of Stage 1). If, during Stage 1 evaluation, less than 2 subjects are observed with a CR, PR, or marrow CR after 3 months of azacitidine in the first 9 subjects with MDS, then enrollment will be stopped. Similarly, if less than 3 subjects are observed with a cPR or cCR after 3 months of azacitidine in the first 18 subjects with JMML, then enrollment will be stopped.

Detailed Study Description

Study Population Pediatric subjects aged 1 month to less than 18 years of age with newly diagnosed conditions of advanced myelodysplastic syndrome (MDS) or juvenile myelomonocytic leukemia (JMML). Length of Study The enrollment period will last for up to 22 months with subjects being treated for a minimum of 3 months and a maximum of 6 months, until transplantation or disease progression (based on an independent central review of responses. Once investigational product (IP) has been discontinued, subjects will then be followed for 2 years after the last dose of investigational product (IP). The follow-up may not be terminated because of new anticancer treatment or hematopoietic stem cell transplantation (HSCT). The End of Trial is defined as either the date of the last visit of the last subject to complete the study, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the Statistical Analysis Plan (SAP), whichever is the later date.

Clinical Study Identifier: NCT02447666

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St. Anna Kinderkrebsforschung, CHILDREN'S CANCER RESEARCH INSTITUTE
Vienna, Austria
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Hopital Universitaire des Enfants
Brussels, Belgium
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University Hospital Ghent
Ghent, Belgium
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University Hospital Motol
Prague 5, Czech Republic
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Centre Hospitalier Universitaire Lyon
Lyon, France
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Hopital d'Enfants de la Timone
Marseille Cedex 01, France
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Universitaetsklinikum Carl Gustav Carus
Dresden, Germany
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Hematology, Oncology and clinical immunology / Heinrich-Heine-University
Dusseldorf, Germany
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Universitatsklinikum Essen
Essen, Germany
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Klinikum der Johann Wolfgang Goethe-Universit t Frankfurt/Main
Frankfurt am Main, Germany
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University of Hamburg
Hamburg, Germany
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Medizinische Hochschule Hannover
Hannover, Germany
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Universitatsklinikum Schleswig-Holstein
Kiel, Germany
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Klinikum der Universitaet Muenchen
Munchen, Germany
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Universitatsklinik Munster
Münster, Germany
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Krankenhaus Barmherzige Bruder Regensburg
Regensburg, Germany
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Universitatsklinikum
Tübingen, Germany
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Our Lady's Hospital for Sick Children
Dublin 12, Ireland
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Policlinico Sant'Orsola-Malpighi
Bologna, Italy
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IRCCS Gaslini Hospital
Genova Quarto, Italy
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Azienda Ospedaliera San Gerardo
Monza, Italy
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IRCCS Policlinico San Matteo
Pavia, Italy
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Regina Margherita Children's Hospital
Torino, Italy
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Hospital Sant Joan de Deu
Barcelona, Spain
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Hospital Infantil Universitario Nino Jesus
Madrid, Spain
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Hospital Universitario Virgen de La Arrixaca
Murcia, Spain
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Queen Silvia Childrens Hospital
Gothenburg, Sweden
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Karolinska University Hospital
Stockholm, Sweden
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Universit ts-Kinderklinik
Zurich, Switzerland
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Great Ormond Street Hospital
London, United Kingdom
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Royal Manchester Children's Hospital
Manchester, United Kingdom
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