Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2015-002855-85
    Sponsor's Protocol Code Number:HO135
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-11-30
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2015-002855-85
    A.3Full title of the trial
    A randomized phase II multicenter study to assess the tolerability and efficacy of the addition of ibrutinib 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.

    A study in the frame of the masterprotocol of parallel randomized phase II studies in UNFIT-older AML/high-risk MDS patients.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A randomized study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabine treatment in patients with AML and high risk myelodysplasia (MDS), UNFIT for intensive chemotherapy, aged >= 66 years.
    A.3.2Name or abbreviated title of the trial where available
    HOVON 135 AML /SAKK 30/15
    A.4.1Sponsor's protocol code numberHO135
    A.5.4Other Identifiers
    Name:METC UMCGNumber:2015.550
    Name:Nederlands TrialregisterNumber:NTR6017
    Name:CCMO dossiernrNumber:NL55164.042.15
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorHOVON Foundation
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportDutch Cancer Society
    B.4.2CountryNetherlands
    B.4.1Name of organisation providing supportJanssen-Cilag International NV
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationHOVON
    B.5.2Functional name of contact pointHOVON Data Center
    B.5.3 Address:
    B.5.3.1Street AddressP.O. Box 2040
    B.5.3.2Town/ cityRotterdam
    B.5.3.3Post code3000 CA
    B.5.3.4CountryNetherlands
    B.5.6E-mailhdc@erasmusmc.nl
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Dacogen
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDecitabine
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDECITABINE
    D.3.9.1CAS number 2353-33-5
    D.3.9.4EV Substance CodeSUB06932MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Imbruvica
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameibrutinib
    D.3.4Pharmaceutical form Capsule, soft
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNibrutinib
    D.3.9.1CAS number 936563-96-1
    D.3.9.3Other descriptive nameIBRUTINIB
    D.3.9.4EV Substance CodeSUB120863
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number140
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Acute Meyloid Leukemia and High Risk Myelodysplastic syndromes
    E.1.1.1Medical condition in easily understood language
    Acute Meyloid Leukemia and High Risk Myelodysplastic syndromes
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10000886
    E.1.2Term Acute myeloid leukemia
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10028533
    E.1.2Term Myelodysplastic syndrome
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - 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.
    E.2.2Secondary objectives of the trial
    - 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.
    - 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 and activities of daily living (ADL) on treatment outcome.
    E.2.3Trial contains a sub-study No
    E.3Principal 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. 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 (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.
    E.4Principal 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 anti-coagulants
    • 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 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
    E.5 End points
    E.5.1Primary end point(s)
    • Cumulative CR/CRi rate after 3 cycles
    E.5.1.1Timepoint(s) of evaluation of this end point
    These endpoints will be evaluated when relevant data for all patients
    are available
    E.5.2Secondary end point(s)
    • Safety and tolerability (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia).
    • Efficacy profile (response rate (CR, CRi, PR), event free survival (EFS) and overall survival (OS)).
    • Days of staying in hospital and transfusion needs.
    • Prognostic value of MRD (by flowcytometry or PCR).
    • Gene mutations predictive of response, EFS and OS by exploratory analysis.
    • 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.
    Translational endpoints:
    • To determine the impact of 3 days ibrutinib monotherapy (pre-treatment) on WBC count, circulating blast count, and kinome (using mass cytometry kinome).
    • To identify potential biomarkers (using mass cytometry kinome; methylome) in bone marrow and peripheral blood which are of prognostic importance in both arms, and whether they are of predictive importance for response.
    • To identify methylome profiles in CD34+ bone marrow blasts and stroma cells which are of prognostic importance in both arms, and whether they are of predictive importance for response.
    E.5.2.1Timepoint(s) of evaluation of this end point
    These endpoints will be evaluated when relevant data for all patients
    are available
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Decitabine treatment without inbrutinib (standard treatment)
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned15
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Lithuania
    Sweden
    Netherlands
    Switzerland
    Germany
    Belgium
    Norway
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 170
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state100
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 170
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation HOVON Foundation
    G.4.3.4Network Country Netherlands
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-11-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-03-18
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 20 06:12:05 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA