C92
Conditions
Interventions
Group 1: SR-patients:
Course 1: CPX-351 (100U/m2/d
Day 1, 3, 5
90 min-Infusion)
Course 2: CPX-351 (100U/m2/d
Day 1, 3
90 min-Infusion)
Course 3: Cytarabine (1g/ m2/12h
Day 1-3
3h-infusion)
Mitoxantrone (7 mg/m2/d, Day 3,4, i.v. – 30 min.-Infusion)
Course 4: hA: Cytarabine (1g/ m2/12h, Day 1-3, 3h-Infusion)
Group 2: HR-patients:
Course 1: CPX-351 (100U/m2/d
Mitoxantrone (7 mg/m2/d, Day 3,4, i.v. – 30 min.-Infusion)
Course 4: HA: Cytarabine (3g/ m2/12h, Day 1-3, 3h-Infusion)
Group 3: Control group (historical):
Course 1: Cytarabine (100 mg/m2/d) on days
Cytarabine (100 mg/m2/12h) on days 3-8
Idarubicine (8mg/m2/d) on days 3,5,7
Etoposide (150 mg/m2/d) on days 6-8
Course 2: Cytarabine (500mg/m2/d) on days 1-4
Idarubicine (5 mg/m2/d) on days 3,5
Course 3: Cytarabine (1g/m2/12h) on days 1-3
Mitoxantrone (7mg/m2/d) on days 3&4
Course 4: Cytarabin (3 g/m2/12 h) on days 1-3
Sponsors
Gesellschaft für pädiatrische Onkologie und Hämatologie (GPOH)
Eligibility
Sex/Gender
All
Age
6 Months to 6 Years
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary objective: Achieving an EFS, which is not inferior to the ML-DS 2006 trial: 5yr-EFS; 87±3% Primary endpoint: 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Objective: • Reduction of toxicity: severe adverse events (CTCAE v4.0 grade III or higher) • To evaluate the response rate • 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 Secondary Endpoint: • 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 (neutrophils < 0.5 Gpt/L). | — |
Countries
Austria, Belgium, Czechia, Denmark, France, Germany, Greece, Hungary, Italy, Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland
Contacts
Public ContactJan-Henning Klusmann
University Clinic Halle (Saale)
Outcome results
None listed