Content - HOVON 135

HOVON 135 - New treatment for elderly leukemia patients

Together with the Haemato Oncology Foundation for Adults in the Netherlands (HOVON), we are conducting the trial HOVON 135 with the aim to improve the treatment for patients who are older than 65 years and who are suffering from leukemia (AML – acute myeloid leukemia) or high-risk myelodysplastic syndrome (MDS), and to better understand the mechanism of these diseases. MDS is a preleukemic disease and very often transforms into a AML that roots in genetically modified stem cells in the bone marrow. Such stem cells are no longer able to produce fully functional blood cells. Patients participating in this trial also suffer from co-existing diseases or have a high risk to become affected by such diseases.

This trial is highly important because elderly patients are the largest patient population that suffers from AML and MDS. However, this patient population is generally underrepresented in clinical trials. In general, an intense chemotherapy is unsuitable for AML and MDS patients who are older than 65 years. Therefore, they get treated with decitabine that acts on the level of the DNA. With our trial, we investigate the effect of the combination of decitabine and ibrutinib on cancer therapy, in different hospitals. Ibrutinib is an active substance that inhibits the protein Bruton-Tyrosinkinase (BTK). This protein supports the growth and survival of cancer cells. We would like to find out how tolerable, safe and effective the combination of these two drugs is as a treatment for elderly patients suffering from AML or MDS. 

Study Chair:

Dr. med. Sabine Blum, CHUV, +41 21 314 42 05

  • Contacts at the hospitals

  • Inclusion criteria

    • 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

    • Patients 66 years and older.

    • Patients NOT eligible for standard chemotherapy, defined as HCT-CI ≥ 3. (Appendix G) or Patient NOT eligible for standard chemotherapy for other reasons (wish of patient).

    • WBC ≤ 30 x109/L (prior hydroxyurea allowed for a maximum of 5 days, stop 2 days before start decitabine treatment)

    • Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values:

      • Serum creatinine ≤ 2.5 mg/dL (≤ 221.7 μmol/L), unless considered AML-related

      • Serum bilirubin ≤ 2.5 x upper limit of normal (ULN), unless considered AML-related or due to Gilbert’s syndrome

      • Alanine transaminase (ALT) ≤ 2.5 x ULN, unless considered AML-relatedWHO performance status 0, 1 or 2 (see Appendix D).

    • Male patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

    •  Written informed consent.

    • Patient is capable of giving informed consent.

  • Exclusion criteria

    • Acute promyelocytic leukemia

    • Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period ( ≤ 5 days) with Hydroxyurea is allowed

    • Diagnosis of any previous or concomitant malignancy is an exclusion criterion: except when the patient completed successfully treatment (chemotherapy and/or surgery and/or radiotherapy) with curative intent for this malignancy at least 6 months prior to randomization.

    • Blast crisis of chronic myeloid leukemia.

    • Inability to discontinue any anti-coagulants (including ascal)

    • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc.)

    • Cardiac dysfunction as defined by:

      • Myocardial infarction within the last 3 months of study entry, or

      • Reduced left ventricular function with an ejection fraction < 40% as measured by MUGA scan or echocardiogram or

      • Unstable angina or

      • New York Heart Association (NYHA) grade IV congestive heart failure (see Appendix I) or

      • Unstable cardiac arrhythmias

    • Patient has had major surgery within the past 4 weeks or a major wound that has not fully healed.

    • Vaccinated with live, attenuated vaccines within 4 weeks prior to randomization.

    • History of stroke or intracranial hemorrhage within 6 months prior to randomization.

    • Patient has a history of human immunodeficiency virus (HIV) or active infection with Hepatitis C or B.

    • Patient has symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement)

    • 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.

Locations for this trial:

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