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    The EU Clinical Trials Register currently displays   37962   clinical trials with a EudraCT protocol, of which   6229   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2013-000536-10
    Sponsor's Protocol Code Number:00103311
    National Competent Authority:Czech Republic - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2013-09-06
    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 ConcernedCzech Republic - SUKL
    A.2EudraCT number2013-000536-10
    A.3Full title of the trial
    A Phase 3, Randomized, Open Label Study Investigating the Efficacy of the BiTE® Antibody Blinatumomab Versus Standard of Care Chemotherapy in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) (TOWER Study)
    Konfirmační multicentrická studie s jedním ramenem k hodnocení
    účinnosti, bezpečnosti a snášenlivosti protilátky blinatumomabu BiTE® u dospělých pacientů s minimálním reziduálním onemocněním (MDR) Bprekurzorovou akutní lymfoblastickou leukémií
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical Phase 3 Study to evaluate the comparative efficacy of the bispecific antibody blinatumomab versus standard of care chemotherapy, in adult subjects with Acute Lymphoblastic Leukemia that did not respond to previous therapy or that relapsed after initially successful previous therapy
    A.3.2Name or abbreviated title of the trial where available
    TOWER Study
    A.4.1Sponsor's protocol code number00103311
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02013167
    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 SponsorAmgen 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 supportAmgen Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmgen (EUROPE) GmbH
    B.5.2Functional name of contact pointIHQ medical Info-Clinical Trials
    B.5.3 Address:
    B.5.3.1Street AddressDammstrasse 23, P.O. Box 1557
    B.5.3.2Town/ cityZug
    B.5.3.3Post codeCH-6300
    B.5.3.4CountrySwitzerland
    B.5.6E-mailMedinfoInternational@amgen.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/3/09/650
    D.3 Description of the IMP
    D.3.1Product nameBlinatumomab
    D.3.2Product code AMG 103, MT103
    D.3.4Pharmaceutical form Powder 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 INNBlinatumomab
    D.3.9.1CAS number 853426-35-4
    D.3.9.2Current sponsor codeAMG 103
    D.3.9.3Other descriptive nameBLINATUMOMAB
    D.3.9.4EV Substance CodeSUB35403
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30.3 (clinical) to 38.5 (commercial)
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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
    Adult patients with relapsed and/or refractory B-precursor Acute lymphoblastic leukaemia
    E.1.1.1Medical condition in easily understood language
    Adult patients with Acute lymphoblastic leukaemia - a cancer of the blood and marrow - which did not completely respond to treatment or has relapsed after first responding to therapy
    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 LLT
    E.1.2Classification code 10000845
    E.1.2Term Acute lymphoblastic leukemia
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10063625
    E.1.2Term Acute lymphoblastic leukemia recurrent
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    evaluate the effect of blinatumomab on overall survival (OS) when compared to standard of care (SOC) chemotherapy
    E.2.2Secondary objectives of the trial
    • evaluate hematological response induced by blinatumomab when compared to SOC chemotherapy
    • evaluate event free survival induced by blinatumomab when compared to SOC chemotherapy
    • evaluate minimal residual disease (MRD) remissions induced by blinatumomab when compared to SOC chemotherapy
    • estimate the effect of blinatumomab on patient reported outcomes, global health status/quality of life (QoL) using the EORTC QLQ-C30
    • evaluate the incidence of allogeneic hematopoietic stem cell transplantation (alloHSCT) and 100-day mortality following HSCT in blinatumomab treated subjects when compared to SOC chemotherapy
    • evaluate the safety of blinatumomab when compared to SOC chemotherapy
    Exploratory:
    • evaluate blinatumomab exposure-response relationships for efficacy and safety
    • assess presence of ALL symptoms as measured by Acute Lymphoblastic Leukemia Symptom Scale (ALLSS)
    • assess the potential for mutations in the tumor DNA to predict resistance to blinatumomab treatment
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subjects with Philadelphia negative B-precursor ALL, with any of the following:
    - refractory to primary induction therapy or refractory to salvage therapy,
    - in untreated first relapse with first remission duration <12 months
    - in untreated second or greater relapse
    - or relapse at any time after allogeneic HSCT
    2. Subject has received intensive combination chemotherapy for the treatment of ALL for initial treatment or subsequent salvage therapy.
    3. Greater than 5% blasts in the bone marrow
    4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
    5. Age ≥ 18 years at the time of informed consent
    6. Subject has provided informed consent or subject’s legally acceptable representative has provided informed consent when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.
    E.4Principal exclusion criteria
    1. History of malignancy other than ALL within 5 years prior to start of protocol-specified therapy with the exception of:
    − Malignancy treated with curative intent and with no known active disease present for 5 years before enrollment and felt to be at low risk for recurrence by the treating physician
    − Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    − Adequately treated cervical carcinoma in situ without evidence of disease
    − Adequately treated breast ductal carcinoma in situ without evidence of disease
    − Prostatic intraepithelial neoplasia without evidence of prostate cancer.
    2. Diagnosis of Burkitt´s Leukemia according to WHO classification
    3. History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis with the exception of history of CNS leukemia that is controlled with intrathecal therapy
    4. Active ALL in the CNS (confirmed by CSF analysis) or testes (no clinical sign thereof)
    5. Isolated extramedullary disease
    6. Current autoimmune disease or history of autoimmune disease with potential CNS involvement
    7. Autologous HSCT within 6 weeks before the start of protocol-specified therapy
    8. Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy
    9. Any active acute Graft-versus-Host Disease (GvHD), grade 2-4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment
    10. Any systemic therapy against GvHD within 2 weeks before start of protocol-specified therapy
    11. Known exclusion criteria to investigator choice of SOC chemotherapy (as per product insert).
    12. Cancer chemotherapy within 2 weeks before start of protocol-specified therapy (intrathecal chemotherapy and dexamethasone are allowed until start of protocol-specified therapy). In addition, any subject whose organ toxicity (excluding hematologic) from prior ALL treatment has not resolved to no more than CTCAE grade 1
    13. Radiotherapy within 2 weeks before the start of protocol-specified therapy
    14. Immunotherapy (e.g., rituximab) within 4 weeks before start of protocol-specified therapy
    15. Subject received prior anti-CD19 therapy
    4.2.16 Abnormal screening laboratory values as defined below:
    − AST (SGOT) and/or ALT (SGPT) and/or ALP ≥ 5 x upper limit of normal (ULN)
    − Total bilirubin (TBL) ≥ 1.5 x ULN (unless related to Gilbert´s or Meulengracht disease)
    − Creatinine ≥ 1.5 ULN or Creatinine clearance < 60 ml/min (calculated)
    17. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive)
    18. Subject is pregnant or breast feeding, or might become pregnant within 24 hours after the last dose of protocol-specified therapy
    19. Woman of childbearing potential and is not willing to use 2 highly effective methods of contraception while receiving protocol-specified therapy and for an additional 24 h after the last dose of protocol-specified therapy.
    20. Currently receiving treatment in another investigational device or
    drug study or less than 30 days since ending treatment on another
    investigational device or drug study(s). Thirty days is calculated from
    Day 1 of protocol-specified therapy.
    21. Other investigational procedures while participating in this study are
    excluded (except for participation in optional sub-studies to this
    protocol).
    22. Subject has known sensitivity to immunoglobulins or any of the
    products or components to be administered during dosing.
    23. Subject previously has randomized into this study or previous
    treatment with blinatumomab.
    24. Subject likely to not be available to complete all protocol-required
    study visits or procedures, including follow-up visits, and/or to comply
    with all required study procedures to the best of the subject and
    Investigator's knowledge.
    25. History or evidence of any other clinically significant disorder,
    condition or disease (with the exception of those outlined above) that, in
    the opinion of the Investigator or Amgen physician, if consulted, would
    pose a risk to subject safety or interfere with the study evaluation,
    procedures or completion.
    E.5 End points
    E.5.1Primary end point(s)
    Overall survival
    E.5.1.1Timepoint(s) of evaluation of this end point
    Assessment when the 330th death is reported in the clinical trial database, 12 months after the last subject is randomized if only 300 to 329 deaths have been reported, or when the 300th death is reported if the study duration exceeds 12 months from the last subject randomized.
    E.5.2Secondary end point(s)
    Key Secondary Efficacy Endpoints (in order of hierarchical testing)
    1. CR within 12 weeks of treatment initiation
    2. CR/CRh*/CRi within 12 weeks of treatment initiation
    3. Event Free Survival (EFS)
    Secondary Efficacy Endpoints
    4. Duration of CR
    5. Duration of CR/CRh*/CRi
    6. MRD remission (defined as MRD level below 10-4 by PCR or flow cytometry) within 12 weeks of treatment initiation
    7. Time to a 10 point decrease from baseline in global health status and QoL scale using EORTC QLQ-C30, or EFS event
    8. AlloHSCT with or without blinatumomab treatment
    Secondary Safety Endpoints
    9. Incidence of adverse events
    10. 100-day mortality after alloHSCT
    11. Incidence of anti-blinatumomab antibody formation
    12. Changes in select vital sign and laboratory parameters
    Exploratory Endpoints
    13. Blinatumomab steady state concentration (Css)
    14. ALLSS score at measured time points
    15. Investigation for mutations in the tumor DNA to predict resistance to blinatumomab treatment
    E.5.2.1Timepoint(s) of evaluation of this end point
    1+2: after 12 weeks; samples are taken at the end of cycles 1 and 2
    3: at the time of relapse, death or EOS
    4+5+15: throughout the study; samples are taken at the end of each cycle, at the safety follow-up visit and every 3 months during long-term follow-up
    6: within 12 weeks of treatment initiation
    7+12+14: troughout treatment and at the safety follow-up visit
    8+9: throughout the study
    10: 100 days after alloHSCT
    11: before first dose, after cycle 2 and at the safety follow-up visit
    13: day 1 and 15 of cycle 1
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    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 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 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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA71
    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
    Austria
    Belgium
    Bulgaria
    Canada
    Czech Republic
    France
    Germany
    Greece
    Ireland
    Israel
    Italy
    Korea, Republic of
    Mexico
    Poland
    Russian Federation
    Spain
    Taiwan
    Turkey
    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
    end of study (primary completion): when the last subject is assessed or receives an intervention for the purposes of final collection of data for the primary endpoint

    end of study (end of trial): when the last subject is assessed or receives an intervention for evaluation in the study; including survival assessments
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    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 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: 308
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 92
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    If the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent, the subject's legally acceptable representative can provide written informed consent.
    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 253
    F.4.2.2In the whole clinical trial 400
    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 Decision2013-10-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-11-07
    P. End of Trial
    P.End of Trial StatusOngoing
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