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   43872   clinical trials with a EudraCT protocol, of which   7291   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:2012-004476-19
    Sponsor's Protocol Code Number:PCYC-1117-CA
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-11-20
    Trial results View 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 ConcernedUK - MHRA
    A.2EudraCT number2012-004476-19
    A.3Full title of the trial
    An Open-label, Single arm, Multicenter Phase 2 Study of the Bruton’s Tyrosine Kinase Inhibitor PCI-32765 (Ibrutinib) in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma with 17p Deletion
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate use of PCI-32765 (Ibrutinib) in Patients with Leukemia
    A.4.1Sponsor's protocol code numberPCYC-1117-CA
    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 pointClinical Trial information
    B.5.3 Address:
    B.5.3.1Street Address995 East Arques Avenue
    B.5.3.2Town/ citySunnyvale, California
    B.5.3.3Post code94085
    B.5.3.4CountryUnited States
    B.5.4Telephone number+14087740330
    B.5.5Fax number+14087740340
    B.5.6E-mailinfo@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 numberEU/3/12/984-EMA/OD/156/11
    D.3 Description of the IMP
    D.3.1Product nameibrutinib
    D.3.2Product code PCI-32765
    D.3.4Pharmaceutical form Capsule
    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 32675 (Ibrutinib)
    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
    An Open-label, Single arm, Multicenter Phase 2 Study of the Bruton’s Tyrosine Kinase Inhibitor PCI-32765 (Ibrutinib) in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma with 17p Deletion
    E.1.1.1Medical condition in easily understood language
    Leukemia
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10003908
    E.1.2Term B-cell small lymphocytic lymphoma
    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 18.0
    E.1.2Level LLT
    E.1.2Classification code 10008976
    E.1.2Term Chronic lymphocytic leukemia
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to evaluate the efficacy of PCI-32765 in terms of ORR according to an Independent Review Committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria in subjects with relapsed or refractory CLL/Small Lymphocytic Lymphoma (SLL) with 17p deletion as determined by fluorescence in situ hybridization (FISH) as determined by central laboratory analysis, who have received a minimum of 1 prior line of systemic treatment.
    E.2.2Secondary objectives of the trial
    • To evaluate duration of response (DOR; including subjects who achieve a PR with lymphocytosis); and
    • To evaluate the safety and tolerability of PCI 32765.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Men or women, at least 18 years of age
    2. Diagnosis of CLL/SLL meeting published diagnostic criteria:22
    • monoclonal B cells (either kappa or lambda light chain restricted) that are clonally
    co-expressing at least 1 B-cell marker (CD19 or CD20) and CD5
    • prolymphocytes may comprise no more than 55% of blood lymphocytes
    3. Documentation of del (17p13.1) confirmed by central laboratory FISH analysis by peripheral blood sample
    4. Must have relapsed or refractory disease after receiving at least 1 prior line of systemic therapy which included at least 2 cycles of chemotherapy or immunotherapy for CLL/SLL.
    5. Currently has active disease meeting at least 1 of the following IWCLL criteria22 for requiring treatment:
    • evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin <110 g/L) and/or thrombocytopenia (platelets <100 x 109/L)
    • 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 LDT of <6 months. Lymphocyte doubling time 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 subjects with initial blood lymphocyte counts of <30 x 109/L, 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 anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy (also see Exclusion Criteria, Section 4.2)
    • documented constitutional symptoms, defined as 1 or more of the following diseaserelated symptoms or signs:
    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. Measurable nodal disease by computed tomography (CT), defined as at least 1 lymph node >1.5 cm in the longest diameter in a site that has not been previously irradiated. An irradiated lesion may be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended.
    7. Eastern Cooperative Oncology Group performance status of 0 or 1
    8. Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥0.75 x 109/L (independent of growth factor support for at least 7 days prior to screening) and platelet count ≥30 x 109/L (independent of transfusion and growth factor support for at least 7 days prior to screening)
    9. Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN)
    10. Total bilirubin ≤1.5 x ULN
    11. Estimated creatinine clearance ≥30 mL/min using the Cockcroft-Gault equation
    12. Ability to receive all outpatient treatment, all laboratory monitoring, and all radiological evaluations at the institution that administers the study drug for the entire study
    13. Male subjects must use an effective barrier method of contraception during the study and for 3 months following the last dose of PCI-32765 if sexually active with a female of
    childbearing potential.
    14. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 3 days of the first dose of PCI-32765 and agree to use dual methods of contraception during the study and for 1 month following the last dose with PCI-32765. Post-menopausal females (>45 years old and without menses for >1 year) and surgically sterilized females are exempt from this criterion.
    15. Ability to provide written informed consent and understand and comply with the requirements of the study
    E.4Principal exclusion criteria
    1. Known involvement of the central nervous system by lymphoma or leukemia
    2. History or current evidence of Richter’s transformation or prolymphocytic leukemia
    3. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura, such as subjects with a declining hemoglobin level or platelet count secondary to autoimmune destruction within the 4 weeks prior to first dose of PCI-32765 or the need for daily corticosteroids ≥20 mg daily to control the autoimmune disease
    4. Prior hematologic stem cell transplantation <6 months from study enrollment or any ongoing GVHD
    5. Received any chemo- or immunotherapy, radiation therapy, or investigational drug within 4 weeks prior to treatment
    6. Received 5 or more prior lines of systemic therapy for CLL
    7. Prior exposure to PCI-32765
    8. Prior enrollment into a PCI-32765 study (subjects who did NOT receive PCI-32765)
    9. Corticosteroid use >20 mg prednisone (or equivalent) within 1 week prior to first dose of PCI-32765, with the exception of inhaled steroid for asthma, topical steroid use, etc.
    Subjects requiring steroids at daily doses >20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or white blood cell (WBC) count lowering are excluded
    10. Major surgery within 4 weeks prior to treatment
    11. History of prior malignancy, with the exception of the following:
    12. Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to Screening and felt to be at low risk for recurrence by treating physician
    13. Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer
    14. Adequately treated cervical carcinoma in situ without current evidence of disease
    15. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia; Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or history of myocardial infarction, unstable
    angina, or acute coronary syndrome within 6 months prior to treatment
    16. Inability to swallow capsules or tablets, or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption (malabsorption syndrome, resection of the small bowel, poorly controlled inflammatory bowel disease, etc.)
    17. Uncontrolled systemic infection or requirement for intravenous (IV) antibiotics
    18. Known infection with human immunodeficiency virus
    19. Serologic status reflecting active hepatitis B or C infection. Subjects who are hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody
    positive will need to have a negative polymerase chain reaction (PCR) result prior to enrollment. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded.
    20. History of stroke or intracranial hemorrhage within 6 months prior to enrollment
    21. Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator’s opinion, could compromise the subject’s safety, or put the study at risk
    22. Requires or has received anticoagulation treatment with warfarin or equivalent Vitamin K antagonists (eg, phenprocoumon) within 28 days of the first dose of PCI-32765
    23. Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor
    24. Woman who is breast-feeding
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is ORR, which is defined as the proportion of subjects in the m-ITT population who achieve a CR, CRi, nPR, or PR, per IWCLL 2008 criteria, based on IRC assessment, over the course of the study in subjects with del 17p CLL as confirmed by central laboratory analysis.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary analysis for all efficacy endpoints will be conducted at approximately 6 months after the last subject’s first dose of PCI-32765, and will be based on IRC assessment and the
    m-ITT population.
    E.5.2Secondary end point(s)
    The secondary endpoint for efficacy is DOR (including subjects who achieve a PR with lymphocytosis), defined as the interval between the date of initial documentation of a response
    including PR with lymphocytosis, and the date of first documented evidence of progressive disease, death, or date of censoring if applicable, for responders only. Subjects who start new anticancer treatment before documentation of disease progression will be censored on the date of the last adequate disease assessment that is on or before the start date of new anticancer therapy. Responders are subjects in the m-ITT population who achieve CR, CRi, PR, or nPR based on
    IWCLL response criteria. Non-responders will be excluded from the analysis for DOR.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The primary analysis for all efficacy endpoints will be conducted at approximately 6 months after the last subject’s first dose of PCI-32765, and will be based on IRC assessment and the
    m-ITT population.
    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 No
    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 Yes
    E.6.13.1Other scope of the trial description
    To evaluate the safety and tolerability of PCI-32765
    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 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 concerned13
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    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
    Belgium
    Canada
    Germany
    Netherlands
    New Zealand
    Sweden
    Turkey
    United Kingdom
    United States
    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
    30 months from last subject enrolled
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    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 years3
    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) Yes
    F.1.2.1Number of subjects for this age range: 45
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 66
    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 state9
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 35
    F.4.2.2In the whole clinical trial 111
    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)
    After completion of PCI 32765, all subjects (except those who withdraw full consent) will undergo a 30-day End-of-Treatment Visit, followed by a long-term Follow-up Phase. During the Follow-up Phase, subjects will be followed for survival and initiation of subsequent anticancer therapy by questionnaire for a minimum of 18 months after the last subject is enrolled. The Follow-up Phase will continue until death, loss to follow up, consent withdrawal, or study end, whichever occurs first.
    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 Decision2012-12-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-01-25
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-04-15
    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 14:59:14 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA