acute myeloid leukemia leukemia
Conditions
Interventions
In the experimental arm selinexor will be added to the standard daunorubicin
cytarabin-arabinoside
in cycle I and to cytarabine-arabinoside in cycle II
The study starts at dose level 60 mg twice week
Acute Myeloid Leukemia
High Risk Myelodysplasia
Sponsors
HOVON
Eligibility
Age
18 Years to 64 Years
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), 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
Exclusion criteria
Exclusion criteria: • Acute promyelocytic leukemia • Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: DLT of selienxor at two dose levels (60 and 80 mg) added to standard chemotherapy DLT is defined as: Death within 31 days of start cycle I Part B: To assess in a randomized comparison the effect of the in Part A selected dose of selinexor on the CR rate. | — |
Secondary
| Measure | Time frame |
|---|---|
| Part B - 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 | — |
Countries
Belgium, Luxembourg, Netherlands, Norway, Switzerland
Outcome results
None listed