ML-DS 2018
Author: Julia Dobke, Last modification: 2021/09/29
https://kinderkrebsinfo.de/doi/e231009
ML-DS 2018 |
Phase III Clinical Trial for CPX-351 in Myeloid Leukemia in Children with Down Syndrome 2018 |
Disease |
Myeloid Leukemia in Children associated with Down Sydrome |
Type |
Prospective, open-label, non-randomized, historically-controlled phase III trial |
Rationale / 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 |
E-Mail |
jan-henning.klusmann@kgu.de
|
URL |
https://www.aml-bfm.de/studienuebersicht/ml-ds-2018/
|
Contact |
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
kkjm.direktor@gmail.com
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
k.waack@forschung-paediatrie.de
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Weitere Informationen |
Sponsor: GPOH gGmbH |