MIDOSTAURIN for Acute myeloid leukemia|Myelodysplastic syndrome

Inclusion criteria

• {"criterion_text":"- A diagnosis of AML and related precursor neoplasms according to WHO 2016 classification (excluding acute promyelocytic leukemia) including secondary AML (after an antecedent hematological disease (e.g. MDS) and therapy-related AML, or a diagnosis of myelodysplastic syndrome with excess of blasts (MDS) and IPSS-R > 4.5"}
• {"criterion_text":"- Patients 18 years and older"}
• {"criterion_text":"- Patients NOT eligible for standard chemotherapy, defined as HCT-CI ≥ 3. (Appendix G) or Patients NOT eligible for standard chemotherapy for other reasons (wish of patient)"}
• {"criterion_text":"- WBC ≤ 30 x109/L (prior hydroxyurea allowed for a maximum of 5 days, stop 2 days before start decitabine treatment)"}
• {"criterion_text":"- Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values: Serum creatinine ≤ 221.7 µmol/L (≤ 2.5 mg/dL ), unless considered AML-related, Serum bilirubin ≤ 2.5 x upper limit of normal (ULN), unless considered AML-related or due to Gilbert’s syndrome, Alanine transaminase (ALT) ≤ 2.5 x ULN, unless considered AML-related"}
• {"criterion_text":"- WHO performance status 0, 1 or 2 (see Appendix D)"}
• {"criterion_text":"- Patient is willing and able to use adequate contraception during and until 5 months after the last protocol treatment"}
• {"criterion_text":"- Written informed consent"}
• {"criterion_text":"- Patient is capable of giving informed consent"}

Exclusion criteria

• {"criterion_text":"- Acute promyelocytic leukemia"}
• {"criterion_text":"- History of stroke or intracranial hemorrhage within 6 months prior to randomization"}
• {"criterion_text":"- Patient has a history of human immunodeficiency virus (HIV) or active infection with Hepatitis C or B"}
• {"criterion_text":"- Patients known to be pregnant"}
• {"criterion_text":"- Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance"}
• {"criterion_text":"- Patients with any serious concomitant medical condition which could, in the opinion of the investigator, compromise participation in the study"}
• {"criterion_text":"- Patients who have senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent"}
• {"criterion_text":"- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule"}
• {"criterion_text":"- Acute leukemia's of ambiguous lineage according to WHO 2016"}
• {"criterion_text":"- Patient has symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement)"}
• {"criterion_text":"- Blast crisis of chronic myeloid leukemia"}
• {"criterion_text":"- Diagnosis of any previous or concomitant malignancy is an exclusion criterion except when the patient completed successfully treatment (chemotherapy and/or surgery and/or radiotherapy) with curative intent for this malignancy at least 6 months prior to randomization OR except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix"}
• {"criterion_text":"- Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period (≤ 5 days) with Hydroxyurea is allowed"}
• {"criterion_text":"- Current concomitant chemotherapy, radiation therapy, or immunotherapy; other than hydroxyurea"}
• {"criterion_text":"- Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc."}
• {"criterion_text":"- Cardiac dysfunction as defined by: Myocardial infarction within the last 3 months of study entry, or reduced left ventricular function with an ejection fraction < 40% as measured by MUGA scan or echocardiogram or unstable angina or New York Heart Association (NYHA) grade IV congestive heart failure (see Appendix I) or unstable cardiac arrhythmias"}

Primary endpoints

• {"endpoint_text":"- Cumulative CR/CRi rate during 3 cycles","definition_or_measurement_approach":"Cumulative CR/CRi rate during 3 cycles (assessed as cumulative complete remission (CR) / CR with incomplete hematologic recovery (CRi) over the first three treatment cycles)"}

Secondary endpoints

• {"endpoint_text":"- Safety and tolerability of midostaurin added to 10-day decitabine treatment for AML (type, frequency, severity and relationship of adverse events to study treatment)","definition_or_measurement_approach":"Type, frequency, severity and relationship of adverse events to study treatment (safety reporting and AE grading)"}
• {"endpoint_text":"- Efficacy profile (response rate after each first three cycles and best response during three cycles and after 9 months (CRMRD-, CR, CRi, MLFS, PR))","definition_or_measurement_approach":"Response rates after each of the first three cycles and best response during three cycles and at 9 months; response categories include CRMRD-, CR, CRi, MLFS, PR"}
• {"endpoint_text":"- Event free survival (EFS)","definition_or_measurement_approach":"Event Free Survival as defined in protocol (time to event measure)"}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"Overall survival (time from randomization to death from any cause)"}
• {"endpoint_text":"- Days of staying in hospital and transfusion needs during three cycles","definition_or_measurement_approach":"Number of hospitalization days and transfusion requirements recorded during first three cycles"}
• {"endpoint_text":"- Prognostic value of MRD (by flowcytometry or PCR)","definition_or_measurement_approach":"MRD measured by flow cytometry or PCR and correlated with clinical outcomes"}
• {"endpoint_text":"- Gene mutations predictive of response, EFS and OS by exploratory analysis","definition_or_measurement_approach":"Exploratory molecular analyses to identify gene mutations predictive of response, EFS and OS"}
• {"endpoint_text":"- Prognostic value of baseline physical and functional conditions using comprehensive geriatric assessment tools (short physical performance battery (SPPB) and activities of daily living (ADL) on treatment outcome","definition_or_measurement_approach":"Baseline SPPB and ADL assessments correlated with treatment outcomes"}
• {"endpoint_text":"- Translational endpoints: to identify potential biomarkers (molecular) that predict for response to decitabine and/or midostaurin","definition_or_measurement_approach":"Identification of molecular biomarkers predictive of response to decitabine and/or midostaurin"}

Belgium

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

11-10-2024

Processing Time Days

10

Number Of Sites

3

Number Of Participants

18

Netherlands

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

09-10-2024

Processing Time Days

8

Number Of Sites

22

Number Of Participants

121

Primary sponsor

Full Name

Haemato Oncology Foundation For Adults Netherlands

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"Netherlands","full_name":"Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"VUmc Stichting","duties_or_roles":"MRD evaluation","organisation_type":"Hospital/Clinic/Other health care facility"}