Phase III clinical trial with CPX-351 for the treatment of myeloid leukemia in children with Down syndrome 2018

Austria, Czechia, Denmark, European Union, France, Germany, Greece, Hungary, Italy, Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland (ICTRP)

Identifiant de l'essai ICTRP
EUCTR2018-002988-25 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
Phase III Clinical Trial for CPX-351 in Myeloid Leukemia in Children with Down Syndrome 2018 (BASEC)

Titre académique
Phase III Clinical Trial for CPX-351 in Myeloid Leukemia in Children with Down Syndrome 2018 (ICTRP)

Titre public
Clinical Trial for the Treatment of Myeloid Leukemia in Children with Down Syndrome (ICTRP)

Maladie en cours d'investigation
Myeloid Leukemia in Children with Down Syndrome;Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15] (ICTRP)

Intervention étudiée

Trade Name: Vyxeos liposomal 44mg/100mg Pulver f?r ein Konzentrat zur Herstellung einer infusionsl?sung
Product Name: Vyxeos
Product Code: CPX-351
Pharmaceutical Form: Powder for concentrate for solution for injection/infusion
INN or Proposed INN: Cytarabine
CAS Number: 147-94-4
Other descriptive name: CYTARABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: DAUNORUBICIN
CAS Number: 20830-81-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 44-

(ICTRP)

Type d'essai
Interventional clinical trial of medicinal product (ICTRP)

Plan de l'étude
Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Prospective, open-label, non-randomized, historically-controlled phase II/III trial If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Historic Control Number of treatment arms in the trial: 1 (ICTRP)

Critères d'inclusion/exclusion
Gender:
Female: yes
Male: yes

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
? Acceptance that vaccination with live vaccines is not possible while participating in the trial
Are the trial subjects under 18? yes
Number of subjects for this age range: 150
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
(ICTRP)

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)

? Diagnosed Wilson?s Disease

?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


Critères d'évaluation principaux et secondaires
Main Objective: ?Achieving an EFS, which is not inferior to the ML-DS 2006 trial: 5yr-EFS; 87?3%;Secondary Objective: ?Reduction of toxicity: severe adverse events (CTCAE v4.0 grade III or higher)
?Identification of prognostic factors concerning the risk of relapse, toxicity and poor outcome
?Evaluate the role of different methods in the determination of minimal residual disease measurement
?Evaluation of somatic SNVs as a predictive biomarker: relation of patients? outcome to the specific somatic SNVs
?Exploration of the role of trisomy 8 as a predictive biomarker
?Exploration of molecular resistance/relapse mechanisms
;Primary end point(s): Event-free survival (EFS), defined as time from diagnosis to the first event or last follow-up. Events are death from any cause, failure to achieve remission, relapse, and secondary malignancy. Failure to achieve remission is considered as an event on day 0.
;Timepoint(s) of evaluation of this end point: After 150 are included and the 5-yrs-follow up is over. (ICTRP)

Secondary end point(s): ?Overall survival (OS), as defined as the time of diagnosis to death from any cause or last follow-up.
?Disease-free survival (DFS)
?Early Response Rate (CR, CRp, CRi)) after induction
?Treatment-related mortality (TRM)
?Minimal residual disease (FACS and NGS)
?Adverse events (according to NCI CTCAE v4.0)
?Duration of myelosuppression
;Timepoint(s) of evaluation of this end point: After 150 are included and the 5-yrs-follow up is over. (ICTRP)

Date d'enregistrement
17.03.2022 (ICTRP)

Inclusion du premier participant
30.06.2022 (ICTRP)

Sponsors secondaires
non disponible

Contacts supplémentaires
Prof. Jan-Henning Klusmann (LKP), KKJM-Direktor@kgu.de, 00496963015094, University Clinic Frankfurt (ICTRP)

ID secondaires
ML-DS2018, 2018-002988-25-DE (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002988-25 (ICTRP)