A randomized phase II multicenter study with a safety run-in to assess the tolerability and efficacy of the addition of oral selinexor (KPT-330) to standard induction chemotherapy in AML and high risk myelodysplasia (MDS) (IPSS-R > 4.5) in patients aged >= 66 years .
- Conditions
- acute myeloid leukemialeukemia10024324
- Registration Number
- NL-OMON44963
- Lead Sponsor
- HOVO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 140
• 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 (see Appendix F)
• Written informed consent.
• Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
• 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Part A:<br /><br>DLT of selienxor at two dose levels (60 and 80 mg) added to standard<br /><br>chemotherapy<br /><br>DLT is defined as: Death within 31 days of start cycle I<br /><br>Part B:<br /><br>To assess in a randomized comparison the effect of the in Part A selected dose<br /><br>of selinexor on the CR<br /><br>rate.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Part B<br /><br>- Overall survival (time from registration till the death of the patient.)<br /><br>- Event free survival (i.e., time from registration to induction failure (i.e.<br /><br>no CR on induction), death or<br /><br>relapse whichever occurs first)<br /><br>- Disease free survival (time from CR on protocol treatment until relapse or<br /><br>death, whichever comes first)<br /><br>- Prognostic value of molecular markers and gene expression profiles of the<br /><br>leukemia assessed at<br /><br>diagnosis<br /><br>- Prognostic value of minimal residual disease (MRD) measurements following<br /><br>therapy by standardized<br /><br>sampling of marrow/blood</p><br>