sluit venster

Log in

Gebruikersnaam Wachtwoord Gebruikersnaam en/of wachtwoord vergeten? Gebruikersnaam en wachtwoord aanvragen

Zoek in de HOVON website

Let op!
Mogelijk ziet u niet alle beschikbare info op deze pagina, omdat u niet bent ingelogd, of omdat u niet de juiste privileges heeft.

Clinical picture: AML (Acute Myeloide Leukemia)

Trial: HOVON 135 AML / SAKK

1. Overview
Study details
2. Patient eligibility criteria
3. Registration (& randomization) of patients
4. Participating parties
5. Participating sites
6. Instruction videos
7. Download documentation / forms

return to top


No news

1. Overview


A program of randomized phase II multicenter studies to assess the tolerability and efficacy of the addition of new drugs to 10-day decitabine in UNFIT (i.e. HCT-CI ≥ 3) AML and high risk myelodysplasia (MDS) (IPSS-R > 4.5) patients aged >= 66 years.




Participating groups; HOVON, SAKK

Uitleg patienten informatie

Beste patient, hieronder vindt u een link naar de patienten informatie die beschikbaar is voor deze studie. Mochten er vragen zijn, dan kunt u deze het beste stellen aan uw behandelend arts.

 Patienten informatie

Study details

Type of study

Prospective randomized Phase II study

Echelon level

Limited site selection

Type of monitoring for this study

Site evaluation visits

Target number of patients


Current number of patients


Date of activation


Date closed


Approved by

The Netherlands:
EC UMCG; 18MAR2016
CA CCMO; 30NOV2015
KWF; 18DEC2015

Study objectives

Primary objectives
To assess in a randomized comparison the effect of ibrutinib added to 10-day decitabine treatment on the cumulative CR/CRi rate after 3 cycles.

Secondary objectives
To assess the safety and tolerability of Ibrutinib added to 10-day decitabine treatment for AML (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia) as regards the selected dose level of the study.
To determine the efficacy profile: response rate (CR, CRi, PR), event free survival (EFS) and overall survival (OS) associated with the two therapy regimens.
To determine the impact of 3 days ibrutinib monotherapy (pre-treatment) on WBC count, circulating blast count, and translational endpoints (mass cytometry).
To measure MRD by immunophenotyping and PCR in relation to clinical response parameters.
To identify potential biomarkers predictive of response, EFS and OS by exploratory analysis (gene mutations, kinome, methylome).
To evaluate the prognostic value of baseline physical and functional conditions using comprehensive geriatric assessment tools (short physical performance battery (SPPB) and activities of daily living (ADL) on treatment outcome).

2. Patient eligibility criteria

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-related
♦ WHO performance status 0, 1 or 2
♦ 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.
♦ 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 hydroxyurea
♦ Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

3. Registration (& randomization) of patients


Central registration at the HOVON Data Center:

TOP address:

Phone number: +31.10.7041560
(working days 9.00 - 17.00)
Fax number: +31.10.7041028

Clinical Trial Center
Erasmus MC Cancer Institute
Postbus 2040
3000 CA Rotterdam

Registration criteria

The following information will be requested:

Protocol number
Institution name
Name of caller/responsible investigator
Date of birth or partial date of birth, e.g. year of birth
Age at date of inclusion
Date written informed consent
Specific items patient gives consent for (see ICF)
Eligibility criteria
Stratification factors

4. Participating parties

Principal Investigator(s)

Prof. G. Huls (UMCG)


Dr. Mrs. V. Havelange (Cliniques Universitaires St. Luc)
Prof. Dr. B. Löwenberg (Erasmus MC)
Prof. Dr. G.J. Ossenkoppele (VUMC)

Coordinating Investigator(s)

Dr. Mrs. S. Blum (Centre Hospitalier Univ. Vaudois)
Dhr. Dr. D.A. Breems (ZNA Stuivenberg)
Dr. B.T. Gjertsen (Haukeland University Hospital)
Prof. Dr. L. Griskevicius (Vilnius University Hospital Santariskiu)


Mrs. Dr. D. Chitu (Erasmus MC - Daniel)

Central Data Manager(s)

Mr. R. Fakkert (Erasmus MC - Daniel)

Monitor - Site Evaluation Visits

Mw. W.M. Keller (Erasmus MC - Daniel)
Mw. J. Kloezeman (Erasmus MC - Daniel)
Mw. T. van de Klundert (Erasmus MC - Daniel)

Other functions

Central Coordinator - Molecular Diagnostics - HO135_MolDiag (Erasmus MC)
Central Coordinator - Molecular Diagnostics - Dhr. Dr. P. Valk (Erasmus MC)
Central Coordinator - MRD - MRD coordination center (VUMC)
Central Coordinator - MRD - Dhr. G.J. Schuurhuis (VUMC)
Reviewer - Cytogenetics - Mw. Dr. H.B. Beverloo (Erasmus MC - Medische Faculteit)
Reviewer - HRC - HRC (Erasmus MC - Daniel)
Reviewer - HRC - Mw. Dr. M. Jongen-Lavrencic (Erasmus MC - Daniel)

Principal investigator

Dr. G. Huls (UMCG)

Trial manager

Marleen Luten (

Central data management

René Hollestein (

Other functions

Please contact monitors at

5. Participating sites

Included patients *
BE-Antwerpen-ZNA Stuivenberg
BE-Haine-Saint-Paul-Hopital de Jolimont
CH-Aarau-Kantonsspital Aarau
CH-Basel-University Hospital Basel
CH-Bellinzona-IOSI, Ospedale Regionale
CH-Fribourg-HFR Hopital Cantonal
CH-Geneve (14)-Hôpital Cantonal Universitaire
CH-Lausanne-Centre Hospitalier Univ. Vaudois
Show 24 more...
* Please note that if TOP is not used to register patients for a study, the number of patients shown is zero.

6. Instruction videos

7. Download documentation / forms


return to top