Acute Myeloid Leukemia (AML), Myelodysplasia
Conditions
Interventions
Patients in this study are treated with 10-day decitabine treatment with or without ibrutinib. The starting dose of ibrutinib will be 560 mg once daily. During the part A run-in phase the dose level o
Sponsors
HOVON Data Center
Eligibility
Inclusion criteria
Inclusion criteria: Patients with: - a diagnosis of AML and related precursor neoplasms according to WHO 2008 classification (excluding acute promyelocytic leukemia) including secondary AML (after an antecedent hematological disease (e.g. MDS) and therapy-related AML, or - acute leukemia's of ambiguous lineage according to WHO 2008 or - a diagnosis of refractory anemia with excess of blasts (MDS) and IPSS-R > 4.5 ♦ Patients 66 years and older. ♦ Patients NOT eligible for standard chemotherapy, defined as HCT-CI >= 3. or Patient NOT eligible for standard chemotherapy for other reasons (wish of patient). ♦ WBC =< 30 x10^9/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 =< 2.5 mg/dL (=< 221.7 ìmol/L), 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. ♦ Male patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. ♦ Written informed consent. ♦ Patient is capable of giving informed consent.
Exclusion criteria
Exclusion criteria: ♦ Acute promyelocytic leukemia. ♦ Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period ( =< 5 days) with Hydroxyurea is allowed ♦ 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. ♦ Blast crisis of chronic myeloid leukemia. ♦ Inability to discontinue any anti-coagulants (including ascal) ♦ 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 ♦ Patient has had major surgery within the past 4 weeks or a major wound that has not fully healed. ♦ Vaccinated with live, attenuated vaccines within 4 weeks prior to randomization. ♦ 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. ♦ Patient has symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement) ♦ 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. ♦ Current concomitant chemotherapy, radiation therapy, or immunotherapy; other than hydroxyurea ♦ Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cumulative CR/CRi rate after 3 cycles | — |
Secondary
| Measure | Time frame |
|---|---|
| ♦ Safety and tolerability (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia). ♦ Efficacy profile (response rate (CR, CRi, PR), event free survival (EFS) and overall survival (OS)). ♦ Days of staying in hospital and transfusion needs. ♦ Prognostic value of MRD (by flowcytometry or PCR). ♦ Gene mutations predictive of response, EFS and OS by exploratory analysis. ♦ 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. Translational outcomes: - To determine the impact of 3 days ibrutinib monotherapy (pre-treatment) on WBC count, circulating blast count, and kinome (using mass cytometry kinome). - To identify potential biomarkers (using mass cytometry kinome; methylome) in bone marrow and peripheral blood which are of prognostic importance in both arms, and whether they are of predictive importance for response. - To identify methylome profiles in CD34+ bone marrow blasts and stroma cells which are of prognostic importance in both arms, and whether they are of predictive importance for response. | — |
Contacts
Public ContactG. Huls
Postbus 30001
Outcome results
None listed