International multicenter, open-label clinical trial for the treatment of acute myeloid leukemia in children and adolescents
- Conditions
- Acute myeloblastic leukaemia [AML]C92.0
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 1050
For 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
• Able to adhere to the study visit schedule and other protocol requirements
• Negative serum pregnancy tests for females of child-bearing potential within 10 days prior to treatment
Group A:
• Diagnosis of an AML (according to WHO classification 2016)
• Acute leukemia of ambiguous lineage (MPAL; according to WHO classification 2016: acute undifferentiated leukemia (AUL, bilineal leukemia; biphenotypic leukemia, dominant myelogenous; lineage switch)
• Children and adolescents < 18 years of age at start of initial chemotherapy
• 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
• Children and adolescents < 18 years of age at start of initial chemotherapy and < 21 years of age at start of this relapsed AML treatment
Group C:
• Patients with AML and indication for first allogenic HSCT of an HLA-identical donor (at least high-resolution typing minimal 9/10,)
• 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
• 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:
• Existing syndromes which exclude treatment including Fanconi anemia or chromosomal instability syndromes
• Patients with trisomy 21 and ML-DS and/or transient myeloproliferative syndrome
• Patients with an acute promyelocytic leukemia (APL), AML with t(15;17)
• Treatment-related or secondary AML
• Symptomatic cardiac dysfunction (CTCAE 5.0 Grade 3 or 4)
• Any other organ dysfunction (CTCAE 5.0 Grade 3 or 4)
• 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
• Participation in another clinical trial with an intervention interfering with the aims of this trial
• Pregnant or breast-feeding patients
• Female and male subjects with child-bearing potential who avoid using highly effective anticonceptive measure(ment)s
• 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:
• Previous-therapy with cytostatic medicines of more than 14 days and other than specified in protocol as allowed prephase
• Diagnosed Wilson´s Disease
Group B:
• Fractional Shortening at echocardiography below 29%
• A Karnofsky performance status < 40% (children = 16 years) or a Lansky performance status of < 40% (children < 16 years) before start of the first course
• impaired liver function: Bilirubin > 3 times upper normal limit; transaminases > 3 times upper normal limit
• History of VOD
• Renal impairment with creatinine < 30 ml/min
• Decompensated haemolytic anaemia
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
• treatment with cytotoxic drugs within 10 days prior to planned study drug administration
• impaired liver function: Bilirubin = 3 times upper normal limit; transaminases = 5 times upper normal limit
• renal impairment with creatinine <30 ml/min
• Cardiac insufficiency requiring treatment; LVEF = 35% (for patients with history of cardiac disease or anthracycline exposure)
• Impaired pulmonary function: PO2 = 70 mm Hg or DLCO = 60%
• requirement of supplementary continuous oxygen
• symptomatic involvement of CNS: leukemic infiltration not cleared by prior intrathecal chemotherapy and/or cranial radiotherapy
• other disease, comorbidity or condition that would severely limit life expectancy
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Group A:<br>Primary endpoint is Event Free Survival (EFS).<br><br>Group B: <br>The primary endpoint is Overall Survival (OS). OS is defined as the time from inclusion to death from any cause. Survivors will be censored at the date of the last follow-up evaluation.<br><br>Group C: A composite endpoint will be used as primary endpoint. Graft-versus host disease, VOD, Relapse Free Survival (GVRDS) is defined as the time from randomization to first failure event.<br>
- Secondary Outcome Measures
Name Time Method Group A: <br>-primary induction failures<br>-risk-group after induction 2, disease-free survival (DFS)<br>-Blast at Induction 1<br>-MRD-level at Induction 1<br>-MRD-level at Induction 2<br><br>Group C:<br>-Graft failure<br>-Engraftment<br>-aGvHD<br>-cGvHD<br>-VOD Grade 3/4<br><br>Group A, C:<br>-overall survival (OS)<br><br>Group B,C:<br>-Event-Free Survival (EFS)<br><br>All groups:<br>-Cumulative incidence of Relapse (CIR)<br>-non-relapse mortality (NMR)<br>-adverse events<br>-early death complete remission (CR)<br>-CNS infestation (CICNS)