A randomized phase II multicenter study to assess the tolerability and efficacy of the addition of midostaurin to 10-day decitabine in UNFIT (i.e. HCT-CI >= 3) adult AML and high risk myelodysplasia (MDS) (IPSS-R > 4.5) patients. A study in the frame of the masterprotocol of parallel randomized phase II studies in UNFIT- AML/high-risk MDS patients.
- Conditions
- Acute myeloid leukemiamyelodysplastic syndromes10024324
- Registration Number
- NL-OMON55438
- Lead Sponsor
- HOVO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 88
• 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.
• 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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Cumulative CR/CRi rate during 3 cycles</p><br>
- Secondary Outcome Measures
Name Time Method