ML-DS 2018

Myeloid Leukemia in Children associated with Down Sydrome

Primary objective

Achieving an event-free survival, which is not inferior to the ML-DS 2006 trial (87±3%).

Secondary objectives

• Reduction of toxicity: severe adverse events (CTCAE v4.0 grade III or higher)
• Evaluation of response
• Identification of prognostic factors (e.g. trisomy 8) concerning the risk of relapse,
• toxicity and poor outcome
• To evaluate the role of different methods in the determination of minimal residual
• disease measurement

The single-arm noninferiority trial will be compared against the historical control (ML-DS 2006 trial) with eventfree survival as the primary endpoint.I will be investigated, whether the substituting of course 1 and 2 of standard ML-DS therapy (defined as ML-DS 2006 protocol) with CPX-351 and reduction of treatment intensity in course 4 for patients with a good response (<0.1% blasts in the bone marrow after course 1) does not result in inferior event-free survival.

• Myeloid Leukemia (ML) or Myelodysplastic Syndrome (MDS), according to WHO
• Trisomy 21: Down syndrome or mosaic
• Age: > 6 months and ≤ 4 years of age with/without GATA1 mutation OR > 4 years of age < 6 years of age with GATA1 mutation
• Morphology/Immunophenotyping: FAB M0, M6 or M7
• Lansky performance score at least equal to 50; or Karnofsky performance status at least equal to 50, whichever is applicable
• Understand and voluntarily provide written permission of parental/legal representative(s) to the ICF prior to conducting any study related assessments/procedures, also concerning data and tumor material transfer according to ICH/GCP and national/local regulations
• Able to adhere to the study visit schedule and other protocol requirements

• Children with Transient Abnormal Myelopoiesis (TAM), according to WHO
• Cytogenetics: AML with recurrent genetic abnormalities (WHO 2016)
• Previous allogeneic bone marrow, stem cell or organ transplantation
• Evidence of invasive fungal infection or other severe systemic infection requiring treatment doses of systemic/parenteral therapy including known active viral infection with human immunodeficiency virus (HIV) or Hepatitis Type B and C
• Symptomatic cardiac disorders (CTCAE 4.0 Grade 3 or 4)
• Major surgery within 21 days of the first dose.
• Any anti-cancer therapy (e.g., intensive chemotherapy, biologics or radiotherapy) for more than 14 days or within 4 weeks before start of therapy, except low-dose cytarabine for the treatment of TAM.
• Concomitant treatment with any other anticancer therapy except those specified in protocol during the study therapy
• Treated by any investigational agent in a clinical study within previous 4 weeks
• History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
• Former Enrolment to this study
• The patient concerned has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities