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   43873   clinical trials with a EudraCT protocol, of which   7292   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:2012-003968-44
    Sponsor's Protocol Code Number:PCYC-1116-CA
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-11-26
    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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2012-003968-44
    A.3Full title of the trial
    An Open-label Extension Study in Patients 65 Years or Older with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Who Participated in Study PCYC-1115-CA (Ibrutinib versus Chlorambucil)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An Open-label Extension Study in Patients 65 Years or Older with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Who Participated in Study PCYC-1115-CA (Ibrutinib versus Chlorambucil)
    A.3.2Name or abbreviated title of the trial where available
    RESONATE-2
    A.4.1Sponsor's protocol code numberPCYC-1116-CA
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01724346
    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 SponsorPharmacyclics LLC
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportPharmacyclics LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPharmacyclics LLC
    B.5.2Functional name of contact pointSenior Director, Regulatory Affairs
    B.5.3 Address:
    B.5.3.1Street AddressMühlentalstrasse 36
    B.5.3.2Town/ citySchaffhausen
    B.5.3.3Post codeCH-8200
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number41525560808
    B.5.5Fax number41525560801
    B.5.6E-mailaterjung@ch.pcyc.com
    D. IMP Identification
    D.IMP: 1
    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 No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEMA/OD/156/11
    D.3 Description of the IMP
    D.3.1Product nameIbrutinib
    D.3.2Product code PCI-32765
    D.3.4Pharmaceutical form Capsule, hard
    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.3.9.2Current sponsor codePCI-32765
    D.3.9.3Other descriptive nameIbrutinib
    D.3.9.4EV Substance CodeSUB88115
    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
    Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
    E.1.1.1Medical condition in easily understood language
    Leukemia (CLL) or Lymphoma (SLL)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10060669
    E.1.2Term B-cell chronic lymphocytic leukemia/prolymphocytic leukemia/small lymphocytic lymphoma
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To monitor progression-free survival (PFS)
    • To continue treatment and safety assessment of patients randomized to Arm B (ibrutinib) in Study PCYC-1115-CA (the parent study) who have not progressed at the time of parent study closure
    • To follow patients for long-term outcome
    • To capture overall response rate (ORR), duration of response (DOR), PFS, and overall survival (OS), and time to next therapy
    • To fulfill long-term follow-up requirements of randomized patients after closure of the parent study, including OS
    E.2.2Secondary objectives of the trial
    Not applicable
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Randomized in the parent study, PCYC-1115-CA
    2. Informed consent for Study PCYC-1116-CA
    3. IRC-confirmed PD in the parent study or closure of the parent study

    To receive second-line ibrutinib, patients must meet all of the following criteria:
    1. IRC-confirmed disease progression in the parent study (PCYC-1115-CA), or for patients who did not progress in the parent study, investigator-determined disease progression in the extension study (PCYC 1116-CA)
    2. Received at least 3 cycles of chlorambucil therapy
    3. Documented, protocol-defined reason for chlorambucil discontinuation:
    • No evidence of response in radiographically assessed disease parameters at Cycle 5 compared to baseline; no further response (defined as failure to reach at least a PR, or a plateau of response with no further improvement of disease parameters) after at least 6 cycles; could not tolerate treatment (a situation defined by the recurrence of toxicity of at least Grade 3 despite appropriate dose reductions and optimal symptomatic management); or maximum treatment of 12 cycles with chlorambucil
    4. Demonstrates continuation of adequate organ function, performance status, and other criteria, as follows:
    • Eastern Cooperative Oncology Group (ECOG) status of 0-2
    • Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 0.75 x109/L (independent of growth factor support in the preceding 7 days) and platelet count ≥ 30 x 109/L (independent of transfusion or growth factor support in the preceding 7 days)
    • Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 1.5 xULN (unless Gilbert's syndrome)
    • Adequate renal function, defined as an estimated glomerular filtration rate ≥ 30 mL/min using the Cockcroft-Gault equation
    • Patients must have recovered from acute toxicities due to prior chemotherapy, radiotherapy, investigational drugs or experimental treatments (non-hematologic toxicities have resolved to a NCI CTCAE (version 4.0) Grade of ≤2) prior to receiving next line ibrutinib on this study
    5. Meets at least 1 of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for active disease requiring treatment (Hallek 2008):
    • Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 10 g/dL), and/or thrombocytopenia (platelets < 100,000/μL)
    • Massive (≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly
    • Massive nodes (at least 10 cm longest diameter), progressive, or symptomatic lymphadenopathy
    • Progressive lymphocytosis with an increase of more than 50% over a 2 month period or a lymphocyte doubling time (LDT) of < 6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of < 30,000/μL, LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.
    • Autoimmune hemolytic anemia and/or immune thrombocytopenia (see definitions below) that is poorly responsive to corticosteroids or other standard therapy
    (Definitions: Autoimmune hemolytic anemia is defined by at least 1 marker of hemolysis [indirect bilirubin above the ULN not due to liver disease, increased lactate dehydrogenase [above ULN] without alternative etiology, or increased absolute reticulocytosis [above ULN] or bone marrow erythropoiesis in the absence of bleeding] AND at least 1 marker of direct or indirect autoimmune mechanism [positive direct antiglobulin for IgG or C3d, cold agglutinins] [Ding 2007]. Autoimmune thrombocytopenia is defined by platelets ≤ 100,000/μL and increased megakaryocytes on the bone marrow examination.)
    • Constitutional symptoms, defined as 1 or more of the following disease-related symptoms or signs, documented in the patient’s record prior to randomization:
    o Unintentional weight loss > 10% within 6 months prior to screening
    o Significant fatigue (inability to work or perform usual activities)
    o Fevers > 100.5°F or 38.0°C for 2 or more weeks prior to screening without evidence of infection
    o Night sweats for more than 1 month prior to screening without evidence of infection
    6. Obtained the sponsor’s approval for second-line ibrutinib therapy
    E.4Principal exclusion criteria
    To receive second-line ibrutinib, patients must meet NONE of the following criteria:
    1. Disease progression involving the central nervous system (CNS) or transformation to another histology
    2. Intervening chemotherapy, immunotherapy, or investigational agent specifically to treat CLL if administered before date of IRC confirmed progressive disease
    3. In the 4 weeks before dosing, radiation therapy, major surgery, or receipt of an investigational drug
    4. Requirement for treatment with a strong CYP3A inhibitor
    5. Uncontrolled systemic infection or requirement for intravenous (IV) antibiotics
    6. Noncompliance on the parent study
    E.5 End points
    E.5.1Primary end point(s)
    • PFS on first-line therapy
    • PFS after initiation of subsequent anticancer therapy (PFS2)
    • Overall survival
    • Time to next treatment
    • ORR and DOR
    • Safety as measured by all AEs and SAEs
    • Disease outcome following cessation of PCI-32765 treatment after attainment of minimal residual disease (MRD)-negative remission in those patients receiving ibrutinib as secondline therapy
    E.5.1.1Timepoint(s) of evaluation of this end point
    Disease assessment measures collected until 25 cycles after the start of treatment in patients taking chlorambucil in the parent. Study assessments occur on Day 1 of every 4th cycle (ie,Cycles 13, 17, 21,25 counting from Cycle 1 Day 1 in the parent study); starting from Cycle 30 onwards, the assessment then occurs every 6 cycles until patient experiences PD or study is closed by the Sponsor. Disease assessment measures collected until 25 cycles after the start of treatment in patients taking ibrutininb in the parent. Study assessments occur on Day 1 of every 4th cycle (counting from Cycle 1 Day 1 in the parent study);starting from Cycle 30 onwards, the assessment then occur every 12 cycles (every 12 months for pre-PD follow-up)until patient experiences PD or study is closed by the Sponsor.
    E.5.2Secondary end point(s)
    Not Applicable
    E.5.2.1Timepoint(s) of evaluation of this end point
    Not Applicable
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    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 No
    E.8.2.4Number of treatment arms in the trial1
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA66
    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
    Australia
    Canada
    China
    Israel
    New Zealand
    United States
    Russian Federation
    Turkey
    Ukraine
    Belgium
    Czechia
    Ireland
    Italy
    Poland
    Spain
    United Kingdom
    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 years10
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years10
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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: 272
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 198
    F.4.2.2In the whole clinical trial 272
    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
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-12-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-02-05
    P. End of Trial
    P.End of Trial StatusCompleted
    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-Mon May 06 18:09:43 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA