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    The EU Clinical Trials Register currently displays   37564   clinical trials with a EudraCT protocol, of which   6160   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2016-003716-12
    Sponsor's Protocol Code Number:C34004
    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:2017-05-15
    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 ConcernedUK - MHRA
    A.2EudraCT number2016-003716-12
    A.3Full title of the trial
    Phase 2 Study of TAK-659 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma After at Least 2 Prior Lines of Chemotherapy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    TAK-659 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
    A.4.1Sponsor's protocol code numberC34004
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03123393
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1187-6208
    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 SponsorMillennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
    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 supportMillennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMillennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
    B.5.2Functional name of contact pointStudy Registration Call Center
    B.5.3 Address:
    B.5.3.1Street Address40 Landsdowne Street
    B.5.3.2Town/ cityCambridge, MA
    B.5.3.3Post code02139
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1866835-2233
    B.5.6E-mailGlobalOncologyMedinfo@takeda.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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code TAK-659
    D.3.4Pharmaceutical form Film-coated tablet
    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 INNTAK-659
    D.3.9.2Current sponsor codeTAK-659
    D.3.9.3Other descriptive nameTAK-659
    D.3.9.4EV Substance CodeSUB179395
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 No
    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.3.2Product code TAK-659
    D.3.4Pharmaceutical form Film-coated tablet
    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 INNTAK-659
    D.3.9.2Current sponsor codeTAK-659
    D.3.9.3Other descriptive nameTAK-659
    D.3.9.4EV Substance CodeSUB179395
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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
    Relapsed or Refractory Diffuse Large B-Cell Lymphoma
    E.1.1.1Medical condition in easily understood language
    Relapsed or Refractory Diffuse Large B-Cell Lymphoma
    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 HLT
    E.1.2Classification code 10012819
    E.1.2Term Diffuse large B-cell lymphomas
    E.1.2System Organ Class 100000004851
    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 the efficacy of TAK-659 as measured by independent radiologic review committee (IRC)-assessed overall response rate (ORR) in patients with diffuse large B-cell lymphoma (DLBCL) - (Stage 2).
    E.2.2Secondary objectives of the trial
    • To assess complete response (CR) rate per IRC in patients with DLBCL - (Stage 2)
    • To select the Stage 2 dose regimen of TAK-659 from the lead-in dose exploration phase (Stage 1) and assess efficacy using ORR per IRC (Stage 2).
    • To assess ORR per IRC at 3, 6, and 9 cycles in patients with DLBCL - (Stage 2).
    • To assess duration of response (DOR) and duration of CR per IRC in patients with DLBCL - (Stage 2).
    • To assess overall response rate (ORR) per IRC in the subgroup of patients with germinal center B-cell (GCB) DLBCL - (Stage 2).
    • To assess ORR per IRC in the subgroup of patients with DLBCL transformed from indolent lymphoma - (Stage 2).
    • To assess progression-free survival (PFS) per IRC in patients with DLBCL - (Stage 2).
    • To assess overall survival (OS) in patients with DLBCL - (Stage 2).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female patients aged 18 years or older.
    2. Patients must have histologically confirmed DLBCL, including de novo disease or transformed disease from indolent NHL. High-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 translocations (double-hit
    DLBCL under DLBCL, NOS, based on the 2008 WHO classification criteria) is not eligible for this study.
    a. Local pathology review for histological confirmation:
    - A formalin-fixed, paraffin-embedded (FFPE) tumor block or appropriately stained slides from a fresh biopsy is required.
    3. Relapsed or refractory to ≥2 prior lines of chemotherapy based on standard of care with certain requirements for prior therapy.
    4. For patients who have relapsed or progressed after achieving a response, documented, investigator-assessed relapse or progression after the last treatment is required.
    5. Must have FDG-PET–avid measurable disease that meets the size criteria per IWG as assessed on cross-sectional imaging by CT/MRI.
    6. ECOG performance status score of 0 or 1.
    7. Life expectancy of >3 months
    8. Patients must have adequate organ function, including the following:
    a. Bone marrow reserve: absolute neutrophil count (ANC) ≥1000/μL, platelet count ≥75,000/μL (≥50,000/μL for patients with bone marrow involvement), and hemoglobin ≥8 g/dL (red blood cell [RBC] and
    platelet transfusion allowed ≥14 days before assessment).
    b. Hepatic: total bilirubin ≤1.5 times the upper limit of the normal range (ULN); ALT and AST ≤2.5xULN.
    c. Renal: creatinine clearance ≥60 mL/min either as estimated by the Cockcroft-Gault equation or based on urine collection (12 or 24 hours).
    d. Others:
    •Lipase ≤1.5xULN and amylase ≤1.5xULN with no clinical symptoms suggestive of pancreatitis or cholecystitis.
    •Blood pressure ≤Grade 1 (hypertensive patients are permitted if their blood pressure is controlled to ≤Grade 1 by hypertensive medications and glycosylated hemoglobin is ≤6.5%).
    E.4Principal exclusion criteria
    1. CNS lymphoma; active brain or leptomeningeal metastases.
    2. Known human immunodeficiency virus (HIV)–related malignancy.
    3. Systemic anticancer treatment (including investigational agents) less than 3 weeks before the first dose of study treatment.
    4. Radiotherapy less than 3 weeks before the first dose of study treatment.
    5. Known HIV positive (testing not required).
    6. Known hepatitis B surface antigen positive or known or suspected active hepatitis C infection.
    7. Prior ASCT within 6 months or prior ASCT at any time without full hematopoietic recovery before Cycle 1 Day 1, or allogeneic stem cell transplant any time.
    8. Participants with certain cardiovascular conditions are excluded.
    9. Major surgery within 14 days before the first dose of study drug or incomplete recovery from any complications from surgery.
    10. Systemic infection requiring parenteral antibiotic therapy or other serious infection (bacterial, fungal, or viral) within 21 days before the first dose of study drug.
    11. Treatment with high-dose corticosteroids for anticancer purposes within 7 days before the first dose of TAK-659.
    12. Patients with another malignancy within 2 years of study start. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection and are
    considered disease-free at the time of study entry.
    13. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-659.
    14. Certain wash-out restrictions before the first dose of study drug on inhibitors of P-gp and/or strong reversible inhibitors of CYP3A, strong CYP3A mechanism-based inhibitors or strong CYP3A inducers and/or Pgp inducers, grapefruit containing food or beverages.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is ORR as assessed by IRC according to the modified 2007 International Working Group (IWG) criteria for malignant lymphoma - (Stage 2).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Primary analysis - after all patients enrolled in the study have had the opportunity to complete 6 cycles of treatment with study drug.
    Conclusion of the study - when OS events have occurred in 70% of patients, or 24 months after last patient in, whichever occurs earlier.
    E.5.2Secondary end point(s)
    • CR rate as assessed by IRC according to the modified 2007 IWG criteria (Stage 2)
    • ORR per IRC according to the 2014 IWG (Lugano) criteria (Stage 2).
    • CR rate per IRC according to the 2014 IWG (Lugano) criteria (Stage 2).
    • ORR per IRC to select the Stage 2 dose regimen of TAK-659 from the lead-in dose exploration phase (Stage 1).
    • ORR per IRC at 3, 6, and 9 cycles, respectively (Stage 2).
    • DOR and duration of CR per IRC (Stage 2).
    • ORR per IRC in patients with GCB DLBCL (Stage 2).
    • ORR per IRC in patients with DLBCL transformed from indolent NHL (Stage 2).
    • PFS per IRC (Stage 2).
    • OS (Stage 2).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Primary analysis - after all patients enrolled in the study have had the opportunity to complete 6 cycles of treatment with study drug.
    Conclusion of the study - when OS events have occurred in 70% of patients, or 24 months after last patient in, whichever occurs earlier.
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    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 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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA40
    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
    Canada
    France
    Germany
    Italy
    Spain
    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
    Conclusion of the study will be considered when OS events have occurred in 70% of patients, or 24 months after last patient in, whichever occurs earlier.
    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 months11
    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 months11
    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: 49
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 73
    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 Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 state13
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 94
    F.4.2.2In the whole clinical trial 122
    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)
    The patient will receive the normal treatment of that condition, at investigator's discretion
    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 Decision2017-06-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-07-18
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-12-17
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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