Behandlung von Patienten mit einer Akuten Myeloischen Leukämie mit einer c-KIT oder FLT3-ITD Mutation in Verbindung mit einer t(8;21) Mutation mit Midostaurin zusätzlich zur Standard-Chemotherapie

Phase 1

• Conditions: Patients with newly diagnosed c-KIT or FLT3-ITD mutated t(8; 21) AML; MedDRA version: 21.1 Level: LLT Classification code 10060557 Term: Acute myelocytic leukemia System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-002567-17-DE
• Lead Sponsor: Technische Universität Dresden

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-09-12
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 18

Inclusion Criteria

• Diagnosis of c-KIT and/or FLT3-ITD mutated t(8;21) AML i.e.
o >20% myeloid blasts in bone marrow and/or peripheral blood at initial diagnosis
o Plus cytogenetic diagnosis of aberration t(8;21)/AML1-ETO
o Plus mutation of c-KIT gene (mut-KIT17 or mut-KIT8) or FLT3-ITD mutation or both c-KIT and FLT3-ITD mutations
• Chemo-responsive disease* as determined by early bone marrow assessment on day 14-16 after first cycle of standard induction therapy with seven-day continuous infusion of 100-200 mg/m2 cytarabine per day in combination with three doses of daunorubicine, or idarubicine, or mitoxantrone
• Age 18 – 65 years
• Fit for intensive chemotherapy as assessed by
o Adequate liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
? Total bilirubin = 1.5 times the upper limit of normal
? ALT and AST = 2.5 times upper limit of normal
? Creatinine = 1.5 times upper limit of normal
o Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF) of >= 50% as assessed by transthoracal twodimensional echocardiography (M Mode”) or MUGA scan
• ECOG performance status of 0-2
• Life expectancy of at least 12 weeks
• Subject's written informed consent has been obtained
• Legal capacity (see also exclusion criterion)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion Criteria

- Primary refractory or previously relapsed AML
- Non-eligibility for high-dose cytarabine based consolidation, e.g. intolerance to cytarabine
- Inability to swallow oral medications
- Symptomatic congestive heart failure as defined by left ventricular ejection fraction (LVEF) of =50% as assessed by transthoracal twodimensional echocardiography (M Mode”) or MUGA scan
- Subject without legal capacity who is unable to understand the nature, significance and consequences of the study
- Investigational drug therapy outside of this trial during or within 4 weeks of study entry
- Known or persistent abuse of medication, drugs or alcohol

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Main Objective: To assess the efficacy of tyrosine-kinase inhibitor midostaurin in c-KIT or FLT3-ITD mutated t(8;21) AML<br> ;Secondary Objective: Not applicable;Primary end point(s): 2-year event-free Survival;Timepoint(s) of evaluation of this end point: evaluation during study and in follow-up visits up to 2 year after study entry

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Time to relapse (TTR), Cumulative incidence of relapse (CIR), Overall survival (OS), Relapse-free survival (RFS), morphologic and molecular CR rate, incidence of AEs/SAEs, MRD kinetics;Timepoint(s) of evaluation of this end point: evaluation during study and in follow-up visits up to 2 year after study entry