ML-DS 2018

Author:  Julia Dobke, Last modification: 2021/09/29

ML-DS 2018

Phase III Clinical Trial for CPX-351 in Myeloid Leukemia in Children with Down Syndrome 2018


Myeloid Leukemia in Children associated with Down Sydrome

Prospective, open-label, non-randomized, historically-controlled phase III trial
Problem / Objectives

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
Therapy / Study arms

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.

Inclusion Criteria
  • 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
Exclusion Criteria
  • 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
Recruitment 150
Status Start in 2021, End: recruitment reached
EudraCT 2018-002988-25
Entry Study Register
Principal Investigator Prof. Dr. med.Jan-Henning Klusmann

Principal investigator

Prof. Dr. med. Jan-Henning Klusmann Universitätsklinikum Frankfurt/Main Direktor der Klinik für Kinder- und Jugendmedizin Theodor-Stern-Kai 7 60590 Frankfurt/Main Telefon +49 69 6301 6489 Fax +49 69 6301 6700

Project management

Katharina Waack-Buchholz Zentrum für Forschungsförderung in der Pädiatrie Pädiatrisches Forschungsnetzwerk Holsterhauser Platz 2 45147 Essen Telefon 0049 201 7494 96 0 Fax 0049 201 8777 5484

Weitere Informationen Sponsor: GPOH gGmbH