A randomized study to assess the tolerability and efficacy of the addition of midostaurin to 10-day decitabine treatment in patients with AML and high risk myelodysplasia (MDS), UNFIT for intensive chemotherapy. ,
- Conditions
- Acute Meyloid Leukemia and high risk myelodysplastic syndromesMedDRA version: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000047-31-NL
- Lead Sponsor
- HOVON Foundation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 140
• Patients with:
- 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
• Patients 18 years and older.
• 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).
• WBC = 30 x109/L (prior hydroxyurea allowed for a maximum of 5 days, stop 2 days before start decitabine treatment)
• 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
• WHO performance status 0, 1 or 2 (see Appendix D).
• Patient is willing and able to use adequate contraception during and until 5 months after the last protocol treatment.
• Written informed consent.
• Patient is capable of giving informed consent.
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 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 126
• Acute promyelocytic leukemia.
• Acute leukemia's of ambiguous lineage according to WHO 2016
• Patient has symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement)
• Blast crisis of chronic myeloid leukemia.
• 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
• Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period ( = 5 days) with Hydroxyurea is allowed
• Current concomitant chemotherapy, radiation therapy, or immunotherapy; other than hydroxyurea
• Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc.)
• 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.
• History of stroke or intracranial hemorrhage within 6 months prior to randomization.
• Patient has a history of human immunodeficiency virus (HIV) or active infection with Hepatitis C or B.
• Patients known to be pregnant
• Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance.
• Patients with any serious concomitant medical condition which could, in the opinion of the investigator, compromise participation in the study.
• Patients who have senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method