patients = 66 years 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 MedDRA version: 20.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemi
Conditions
Interventions
Product Name: selinexor (20 mg)
Product Code: KPT-330
Pharmaceutical Form: Tablet
INN or Proposed INN: selinexor
Current Sponsor code: KPT-330
Other descriptive name: KPT-330
Concentration unit: mg mi
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients eligible for standard chemotherapy. • Patients 66 years and older • 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 • Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values: - 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. - Serum bilirubin = 2.5 x upper limit of normal (ULN) - Aspartate transaminase (AST) = 2.5 x ULN - Alanine transaminase (ALT) = 2.5 x ULN - Alkaline phosphatase = 2.5 x ULN • WHO performance status 0, 1 or 2 (see Appendix F) • 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 230
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: - Basal and squamous cell carcinoma of the skin - 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: - Myocardial infarction within the last 6 months of study entry, or - Reduced left ventricular function with an ejection fraction < 50% ad measured by MUG scan or echocardiogram or - Unstable angina or - New York Heart Association (NYHA) grade II or greater congestive heart failure (see Appendix I) or - 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 |
|---|---|
| Main Objective: For part A of the study (if applicable): 1. To assess the safety and tolerability of selinexor added to standard induction chemotherapy for AML (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia) and select the feasible dose level for part B 2. To assess in a randomized comparison the effect of selinexor on the CR rate. For part B: 1. To assess the safety and tolerability of selinexor added to standard induction chemotherapy for AML (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia) as regards the selected dose level of selinexor 2. To assess in a randomized comparison the effect of selinexor on the CR rate. ;Secondary Objective: For part B: 1. To determine the efficacy profile (event free survival (EFS) disease free survival (DFS) and overall survival (OS)) associated with the two therapy regimens. 2. To measure MRD by immunophenotyping in relation to clinical response parameters. 3. To identify potential biomarkers predictive of response, EFS, DFS and OS by exploratory genomic analysis (microarray, gene mutations) ;Primary end point(s): • Incidence of DLT (part A) • The effect of selinexor on the CR rate (part B of study) ;Timepoint(s) of evaluation of this end point: The final analysis of the primary endpoints will be done one year after last patient is registered in the selinexor arm | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 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 ;Timepoint(s) of evaluation of this end point: The final analysis of the secondary endpoints will be done one year after the last patient is registered in the selinexor arm | — |
Countries
Belgium, Netherlands, Norway, Switzerland
Contacts
Public ContactHOVON Data Center
Erasmus MC Cancer Institute, Clinical Trial Center
Outcome results
None listed