Study With Azacitidine in Pediatric Subjects With Newly Diagnosed Advanced Myelodysplastic Syndrome (MDS) and Juvenile Myelomonocytic Leukemia (JMML)
Condition: Myelodysplastic Syndrome; Leukemia, Myelomonocytic, Juvenile
MeSH terms: Leukemia; Preleukemia; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      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. If matched
      pair is not viable then other methodologies will be explored to evaluate and compare response
      rates reported in literature and also in registry database 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 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 1 year 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.
    

Intervention name(s): Azacitidine
Intervention type(s): Drug
Other intervention name(s): Vidaza
Intervention MeSH terms: Azacitidine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Azacitidine; Myelodysplastic syndrome; Juvenile myelomonocytic leukemia; Hematopoietic stem cell transplantation; Vidaza; Hypomethylating agent