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    The EU Clinical Trials Register currently displays   43874   clinical trials with a EudraCT protocol, of which   7293   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).

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    Summary
    EudraCT Number:2014-001977-15
    Sponsor's Protocol Code Number:KCP-330-009
    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:2016-02-02
    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 number2014-001977-15
    A.3Full title of the trial
    A Phase 2b Open-label Study of Selinexor (KPT-330) in Patients with
    Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2b Open-label Study of Selinexor (KPT-330) in Patients with
    Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
    A.3.2Name or abbreviated title of the trial where available
    SADAL: Selinexor Against Diffuse Aggressive Lymphoma
    A.4.1Sponsor's protocol code numberKCP-330-009
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02227251
    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 SponsorKaryopharm Therapeutics, Inc.
    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 supportKaryopharm Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKaryopharm Therapeutics, Inc.
    B.5.2Functional name of contact pointClinical Trial Information Desk
    B.5.3 Address:
    B.5.3.1Street Address85 Wells Ave
    B.5.3.2Town/ cityNewton
    B.5.3.3Post codeMA 02459
    B.5.3.4CountryUnited States
    B.5.6E-mailclinicaltrials@karyopharm.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/3/14/1317
    D.3 Description of the IMP
    D.3.1Product nameSelinexor 20mg coated tablets
    D.3.2Product code KPT-330
    D.3.4Pharmaceutical form 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 INNSelinexor
    D.3.9.1CAS number 1393477-72-9
    D.3.9.2Current sponsor codeKPT-330
    D.3.9.4EV Substance CodeSUB168135
    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/Refractory DLBCL
    E.1.1.1Medical condition in easily understood language
    Relapsed/Refractory DLBCL
    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 Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of selinexor 60 mg in comparison to a minimally
    effective lower threshold level of ORR of 15% in patients with R/R
    DLBCL.
    E.2.2Secondary objectives of the trial
    • To determine DOR
    • To determine the disease control rate (DCR)
    • To assess the safety profile of selinexor
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    The study population under evaluation will consist of male and female patients aged 18 years or older. To be included in this study, a patient must meet all the following criteria:
    1. Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
    2. Age ≥18 years
    3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 (Appendix 2)
    4. Patients should have estimated life expectancy of >3 months at study entry
    5. Previously treated, pathologically confirmed de novo DLBCL, or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma)
    6. Patients must have received at least 2 but no more than 5 previous systemic regimens for the treatment of their de novo or transformed DLBCL including (i) at least one course of anthracycline-based chemotherapy (unless absolutely contraindicated due to cardiac dysfunction, in which case other active agents such as etoposide, bendamustine or gemcitabine must have been given) and (ii) at least one course of anti-CD20 immunotherapy (e.g., rituximab), unless contraindicated due to severe toxicity. Patients who were considered ineligible for standard multi-agent immunochemotherapy must have received at least two and no more than five prior treatment regimens including at least one course of anti-CD20 antibodies and must be approved by the Medical Monitor. Prior stem cell transplantation is allowed; induction, consolidation, stem cell collection, preparative regimen and transplantation ± maintenance are considered a single line of therapy.
    7. For patients whose most recent systemic anti-DLBCL therapy induced
    a PR or CR, at least 60 days must have elapsed since the end of that
    therapy. For all other patients, at least 14 weeks (98 days) must have
    elapsed since the end of their most recent systemic anti DLBCL therapy.
    Palliative localized radiation within the therapy-free interval is allowed.
    Non chemotherapy maintenance will not be considered anti DLBCL
    therapy, and therefore is allowed during the therapy-free interval .
    8. Documented clinical or radiographic evidence of progressive DLBCL prior to dosing.
    9. Patients must have measurable disease per the revised criteria for response assessment of lymphoma (Cheson 2014). Lymph nodes should be considered abnormal if the long axis is > 1.5 cm, regardless of the short axis. If a lymph node has a long axis of 1.1 to 1.5 cm, it should only be considered abnormal if its short axis is > 1.0. Lymph nodes ≤ 1.0 by ≤ 1.0 will not be considered abnormal for relapse or PD.
    10. Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use reliable methods of contraception for three months after their last dose of medication. Male patients must use a reliable method of contraception if sexually active with a female of child-bearing potential.. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose (see Section 13.5.2.1 Permitted Concomitant Medication – Prevention of Pregnancy for description of acceptable contraceptive methods).
    E.4Principal exclusion criteria
    Patients meeting any of the following exclusion criteria are not eligible to enroll in this study.
    1. Patients who are pregnant or lactating
    2. DLBCL with mucosa-associated lymphoid tissue [MALT] lymphoma, composite lymphoma (HL+NHL), or DLBCL transformed from diseases other than indolent NHL
    3. Primary mediastinal (thymic) large B-cell lymphoma (PMBL)
    4. Patients must not be eligible for high-dose chemotherapy with autologous stem cell transplantation rescue (investigator must provide detailed documentation for ineligibility)
    5. Known central nervous system (CNS) lymphoma or meningeal involvement
    6. For patients whose most recent systemic anti-DLBCL therapy induced a PR or CR: Radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy other than glucocorticoids < 60 days prior to Cycle 1 Day 1
    7. For patients whose most recent systemic anti-DLBCL therapy did not induce a PR or CR: Radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy other than glucocorticoids < 14 weeks prior to Cycle 1 Day 1
    8. Patients who have not recovered to Grade ≤ 1 clinically significant AEs, or to their baseline, from their most recent systemic anti DLBCL therapy
    9. Patients with active graft-versus-host disease after allogeneic stem cell transplantation. At least 4 months must have elapsed since completion of allogeneic stem cell transplantation.
    10. Major surgery within 2 weeks of first dose of study treatment.
    11. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient’s safety
    12. Unstable cardiovascular function:
    • Symptomatic ischemia, or
    • Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded), or
    • Congestive heart failure (CHF) of NYHA Class ≥3, or
    • Myocardial infarction (MI) within 3 months
    13. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral
    14. Active Hepatitis B or Hepatitis C infection
    15. Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study)
    16. Patients unable to swallow tablets, patients with malabsorption syndrome, or any other GI disease or GI dysfunction that could interfere with absorption of study treatment
    17. Any of the following laboratory abnormalities:
    a) Absolute neutrophil count (ANC) <1000 cells/mm3 or platelet count <75,000/mm3 during screening and on C1D1. Use of granulocyte-stimulating factors and platelet growth factors prior to and during the study is acceptable
    b) A circulating lymphocyte count of >50,000/ul
    c) Hepatic dysfunction: bilirubin >2.0 times the upper limit of normal (ULN) (except patients with Gilbert’s syndrome: total bilirubin of > 3 x ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2.5 times ULN. In patients with known liver involvement of their DLBCL, AST and ALT >5 x ULN.
    d) Severe renal dysfunction: estimated creatinine clearance of < 30 mL/min, measured in 24 hour urine or calculated using the formula of Cockroft and Gault [(140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female]
    e) Hematopoietic dysfunction: hemoglobin < 10.0 g/dL within 14 days of and including Cycle 1 Day 1 and/or patients receiving red blood cell (RBC) transfusion within 14 days of and including Cycle 1 Day 1
    18. Patients with a body surface area (BSA) < 1.4 m2 as calculated per Dubois 1916 or Mosteller 1987
    19. Psychiatric illness or substance use that would prevent the patient from giving informed consent or being compliant with the study procedures
    20. Persons who have been committed to an institution by official or judicial order
    21. Patients with dependency on the sponsor, investigator or study site
    E.5 End points
    E.5.1Primary end point(s)
    Objective disease response assessment will be made according to the
    revised criteria for response assessment of lymphoma (Cheson, 2014).
    The data used for primary statistical analysis will be provided by the
    central imaging laboratory.
    The primary endpoint of ORR will be assessed as the ORR of selinexor 60
    mg compared to a minimally effective lower threshold level of ORR of
    15%.

    • The ORR is defined as the proportion of patients who achieve either CR
    or PR.
    • Progression is defined as the first occurrence of PD per the revised
    response criteria. Clinical disease progression in the absence of formal
    criteria for PD should be radiographically confirmed whenever possible
    and must be comprehensively documented by the treating physician.
    Patients who have clinical disease progression in the absence of formal
    criteria for PD or radiographical confirmation will be censored at the
    time of last non-PD adequate response assessment.
    • DOR is defined as the duration of time from first occurrence of CR or
    PR until the first date that disease progression is objectively
    documented
    • DCR is defined as the proportion of patients who achieve CR, PR, or SD
    for a minimum of 4 weeks, following randomization/enrollment (i.e.,
    ORR + SD)
    • PFS is defined as the duration of time from randomization/enrollment
    until progression or death due to any cause. A sensitivity analysis will
    also be performed for PFS where death will be included if it may be
    reasonably attributed to the patient's underlying DLBCL.
    • OS is defined as the duration of time from randomization/enrollment
    until death due to any cause. A sensitivity analysis will also be
    performed for OS where death will be included if it may be reasonably
    attributed to the patient's underlying DLBCL.
    • Each patient's TTP on selinexor compared with the TTP of his/her most
    recent prior therapy. TTP is defined as the duration of time from the
    date of randomization/enrollment until the date of progression.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Disease response will be assessed by the revised criteria for response
    assessment of lymphoma (Cheson, 2014; Appendix 1) in patients on
    Cycle 3 Day 1 (±1 week) and then every 8 weeks ± 1 week (i.e., Day 1 of
    odd numbered cycles) until disease progression is confirmed by the
    central imaging laboratory. There is no maximum treatment duration.
    E.5.2Secondary end point(s)
    Secondary Efficacy Endpoints
    • DOR, defined as the duration of time from first occurrence of CR or PR until the first date that recurrence of disease progression is objectively documented, for each dose level
    • DCR, defined as the proportion of patients who achieve CR, PR, or SD for a minimum of 4 weeks following start of therapy, compared for High-Sel and Low-Sel regimens

    Secondary Safety Endpoints
    • Safety endpoints include AE reports, ECOG performance status, vital signs, physical examinations, ECGs, ophthalmic examinations, concomitant medications and laboratory safety evaluations.
    E.5.2.1Timepoint(s) of evaluation of this end point
    End of study
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA82
    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
    Austria
    Belgium
    Bulgaria
    Canada
    France
    Germany
    Hungary
    Israel
    Italy
    Netherlands
    Poland
    Serbia
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    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
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    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: 159
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 161
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 220
    F.4.2.2In the whole clinical trial 320
    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 a patient has ceased his/her participation in the study, his/her medical doctor will offer the most appropriate treatment currently available.
    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 Decision2016-02-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-07-01
    P. End of Trial
    P.End of Trial StatusOngoing
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