International multicenter, open-label clinical trial for the treatment of acute myeloid leukemia in children and adolescents

Who can take part

• All Groups: 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 biomaterial transfer according to ICH/GCP and national/local regulations
• Group C: Patients with AML and indication for first allogenic HSCT
• Group C: Age at time of inclusion from 1 month (28 days) to less than 18 years at diagnosis; up to 21 years at time of HSCT
• Group C: Criteria for allogeneic HSCT: o in AML complete remission (CR) o available MSD, MFD or MUD; matched is defined as at least 9/10 after 4 digit typing for HLA-A, B, C, DRB1, DQB1 loci
• All Groups: Able to adhere to the study visit schedule and other protocol requirements
• All Groups: Negative serum pregnancy tests for females of child-bearing potential within 10 days prior to treatment
• Group A: Diagnosis of de-novo AML (according to WHO classification 2016)
• Group A: Acute leukemia of ambiguous lineage (MPAL; according to WHO classification 2016: acute undifferentiated leukemia (AUL, bilineal leukemia; biphenotypic leukemia, dominant myelogenous; lineage switch)
• Group A: Children and adolescents < 18 years of age at start of initial chemotherapy
• Group A: Acceptance that vaccination with live vaccines is not possible while participating in the trial
• Group B: Patients with first relapsed (including relapse after SCT) or primary refractory AML
• Group B: Children and adolescents < 18 years of age at start of initial chemotherapy and < 21 years of age at start of this relapsed AML treatment

Who cannot take part

• Group A: Previous therapy with cytostatic medicines of more than 14 days and other than specified in protocol as allowed prephase
• Group C: Treatment with cytotoxic drugs within 10 days prior to planned study drug administration
• Group C: Symptomatic involvement of CNS: leukemic infiltration not cleared by prior intrathecal chemotherapy and/or cranial radiotherapy
• All Groups: Any other organ dysfunction (CTCAE 5.0 Grade 4) that will interfere with the administration of the therapy according to this protocol
• All Groups: Existing syndromes which exclude treatment including Fanconi anemia or other chromosomal instability syndromes
• All Groups: Hypersensitivity to the active substance or other excipients contained in the investigational medical product listed in the summary of product characteristics (SmPC) or Investigators Brochure (IB)
• Group A: Diagnosed Wilson’s Disease
• Group B: History of VOD
• All Groups: Patients with trisomy 21 and ML-DS and/or transient myeloproliferative syndrome
• Group C: Other disease, comorbidity or condition that would severely limit life expectancy
• All Groups: Symptomatic cardiac dysfunction (CTCAE 5.0 Grade 3 or 4)
• All Groups: Evidence of uncontrolled 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
• Group B: Impaired liver function: Bilirubin > 3 times upper normal limit; transaminases > 3 times upper normal limit
• Group B: Renal impairment with creatinine < 30 ml/min
• Group C: Impaired liver function: Bilirubin ≥ 3 times upper normal limit; transaminases ≥ 5 times upper normal limit
• Group C: Renal impairment with creatinine < 30 ml/min
• Group C: Cardiac insufficiency requiring treatment; LVEF ≤ 35% (for patients with history of cardiac disease or anthracycline exposure)
• Group B: A Karnofsky performance status < 40% (children ≥ 16 years) or a Lansky performance status of < 40% (children < 16 years) before start of the first course
• Group C: A Karnofsky performance status < 60% (children ≥ 16 years) or a Lansky performance status of < 60% (children < 16 years) before start of the Group treatment
• All Groups: Female and male subjects with child-bearing potential who avoid using highly effective contraconceptive measure(ment)s
• Group B: Fractional Shortening at echocardiography below 29%
• Group B: Decompensated haemolytic anaemia
• Group C: Impaired pulmonary function: PO2 ≤ 70 mm Hg or DLCO ≤ 60%
• Group C: Requirement of supplementary continuous oxygen
• All Groups: Patients with an acute promyelocytic leukemia (APL), AML with t(15;17)
• All Groups: Treatment-related or secondary AML
• All Groups: Participation in another clinical trial with an intervention interfering with the aims of this trial
• All Groups: Pregnant or breast-feeding patients