Content - HOVON 103 SEL

HOVON 103 SEL / SAKK 30/10 - Tolerability and effectiveness of Selinexor for AML patients

In this phase II trial, we investigate together with HOVON (the Haemato Oncology Foundation for Adults in The Netherlands) the tolerability and the effectiveness of the drug Selinexor (KPT-330) in combination with the standard therapy. The standard therapy for acute myeloid leukemia (rare, acute cancer of the blood-forming organs) is an intensive chemotherapy. Selinexor is a new drug that retains Tumor-suppressor proteins within the cell nucleus leading to an improved regulation of the tumor growth. This potentially leads to an better tumor control.

This trails focus’ on elderly patients (66 years or older), which are fit enough for intensive chemotherapy. Although there has been some progress in this patient population the results are not satisfactory and there is a need for improvement.

Study Chair:

PD Dr. med. Georg Stüssi, IOSI, +41 91 811 87 78

  • Contacts at the hospitals

  • 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.
  • 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

Locations for this trial:

Kantonsspital Aarau
Tellstrasse 25
0 5001 Aarau
Universitätsspital Basel
Petersgraben 4
0 4031 Basel
Istituto Oncologico della Svizzera Italiana IOSI
Via Ospedale
0 6500 Bellinzona
Inselspital
Freiburgstrasse 8
3010 Bern
Hôpital Fribourgeois HFR
Chemin des Pensionnats 2
1708 1708 Fribourg
Hôpitaux Universitaires de Genève HUG
Rue Gabrielle-Perret-Gentil 4
0 1205 Genève
Centre Hospitalier Universitaire Vaudois CHUV
Rue du Bugnon 46
0 Lausanne
Kantonsspital Luzern
Spitalstrasse
0 6000 Luzern
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen
UniversitätsSpital Zürich
Rämistrasse 100
0 8091 Zürich