Acute Myeloid Leukemia (AML), MDS
Conditions
Interventions
2. Arm C: Cycle I: Dauno/Cytarabine/Selinexor, cycle II: Cytarabine/Selinexor.
Sponsors
HOVON Data Center
Eligibility
Inclusion criteria
Inclusion criteria: • Patients eligible for standard chemotherapy. • Patients 66 years and older • Patients with: o 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 o acute leukemia’s of ambiguous lineage according to WHO 2008 or o a diagnosis of refractory anemia with excess of blasts (MDS) and IPSS-R > 4.5 • Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values: o Serum creatinine ≤1.0 mg/dL (≤88.7 μmol/L); if serum creatinine >1.0 mg/dL (>88.7 μmol/L), then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where the Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine in mg/dL)-1.154 x (age in years)-0.203 x (0.742 if patient is female) x (1.212 if patient is black) NOTE: if serum creatinine is measured in μmol/L, recalculate it in mg/dL according to the equation: 1 mg/dL = 88.7 μmol/L and use the above mentioned formula. o Serum bilirubin ≤ 2.5 x upper limit of normal (ULN) o Aspartate transaminase (AST) ≤ 2.5 x ULN o Alanine transaminase (ALT) ≤ 2.5 x ULN o Alkaline phosphatase ≤ 2.5 x ULN • WHO performance status 0, 1 or 2 • Written informed consent. • Male and female patients must use an effective contraceptive method if relevant during the study and for a minimum of 6 months after study treatment.
Exclusion criteria
Exclusion criteria: • Acute promyelocytic leukemia • Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period (< 2 weeks) with Hydroxyurea is allowed • Concurrent history of active malignancy in the two past years prior to diagnosis except for: o Basal and squamous cell carcinoma of the skin o in situ carcinoma of the cervix • Blast crisis of chronic myeloid leukemia • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etcetera) • Cardiac dysfunction as defined by: o Myocardial infarction within the last 6 months of study entry, or o Reduced left ventricular function with an ejection fraction < 50% ad measured by MUG scan or echocardiogram or o Unstable angina or o New York Heart Association (NYHA) grade II or greater congestive heart failure (see Appendix I) or o Unstable cardiac arrthythmias • 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 as specified in the protocol. • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Incidence of DLT (part A) • The effect of selinexor on the CR rate (part B of study) | — |
Secondary
| Measure | Time frame |
|---|---|
| • Overall survival (time from registration till the death of the patient.) • Event free survival (i.e., time from registration to induction failure (i.e. no CR on induction), death or relapse whichever occurs first) • Disease free survival (time from CR on protocol treatment until relapse or death, whichever comes first) • Prognostic value of molecular markers and gene expression profiles of the leukemia assessed at diagnosis • Prognostic value of minimal residual disease (MRD) measurements following therapy by standardized sampling of marrow/blood | — |
Contacts
Public ContactG.J. Ossenkoppele
VUMC, Afd. Hematologie Postbus 7057
Outcome results
None listed