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   43861   clinical trials with a EudraCT protocol, of which   7284   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:2016-002044-16
    Sponsor's Protocol Code Number:20150292
    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:2016-08-29
    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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2016-002044-16
    A.3Full title of the trial
    A Phase 2/3 Multi-center Study of Evaluate the Safety and Efficacy of Blinatumomab in Subjects with Relapsed/Refractory Aggressive B-Cell Non Hodgkin Lymphoma
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical phase 2/3 study to investigate the safety and efficacy of Blinatumomab in subjects with Non Hodgkin Lymphoma that did not respond to previous therapy or that relapsed after initially successful previous therapy
    A.4.1Sponsor's protocol code number20150292
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02910063
    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 pointMedical Information
    B.5.3 Address:
    B.5.3.1Street AddressDammstrasse 23, P.O. Box 1557
    B.5.3.2Town/ cityZug
    B.5.3.3Post codeCH-6301
    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 Yes
    D.2.1.1.1Trade name Blincyto
    D.2.1.1.2Name of the Marketing Authorisation holderAmgen Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.1Product nameBlinatumomab
    D.3.2Product code AMG 103, MT103
    D.3.4Pharmaceutical form Powder for concentrate 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.3.9.4EV Substance CodeSUB35403
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number38.5
    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
    Subjects with Relapsed/Refractory Aggressive B-Cell Non-Hodgkin Lymphoma (B-NHL)
    E.1.1.1Medical condition in easily understood language
    Subjects with Non-Hodgkin Lymphoma 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 20.0
    E.1.2Level PT
    E.1.2Classification code 10020067
    E.1.2Term High grade B-cell lymphoma Burkitt-like 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 20.0
    E.1.2Level PT
    E.1.2Classification code 10036710
    E.1.2Term Primary mediastinal large B-cell 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 20.0
    E.1.2Level PT
    E.1.2Classification code 10063908
    E.1.2Term Non-Hodgkin's lymphoma unspecified histology aggressive
    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 20.0
    E.1.2Level PT
    E.1.2Classification code 10012818
    E.1.2Term Diffuse large B-cell lymphoma
    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
    Phase 2:
    • estimate the complete metabolic response (CMR) rate following blinatumomab monotherapy administered in the second salvage (S2) treatment of transplant-eligible subjects with relapsed or refractory (R/R) aggressive B-NHL who have not achieved CMR1 following 2 cycles of standard platinum-based first salvage (S1) chemotherapy
    Phase 3:
    • compare the CMR rates following blinatumomab to those following investigator’s choice (IC) S2 chemotherapy
    E.2.2Secondary objectives of the trial
    Phase 2:
    • To evaluate the efficacy parameters following blinatumomab treatment, of:
    - Response duration
    - The rate of successful hematopoietic stem cell mobilization
    • To evaluate the safety of blinatumomab in the S2 setting
    Phase 3:
    • To compare the efficacy of blinatumomab to investigator’s choice chemotherapy (ICC) in:
    - Overall survival
    - Response duration
    - Rate of successful HSCs mobilization
    - Ability to proceed to hematopoietic stem cell transplant (both autologous and allogeneic) rates among responding subjects (CMR) or those in sustained partial metabolic response (PMR)
    - Objective response rate (ORR; CMR + PMR)
    • To compare the safety profile of blinatumomab to that of ICC
    • To compare the quality of life reported by subjects treated with blinatumomab or ICC
    Phases 2 and 3
    • To characterize the pharmacokinetic parameters of blinatumomab administered to subjects with R/R aggressive B-NHL
    • Progression-free survival
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject has provided informed consent prior to initiation of any study-specific activities/procedures OR subject’s legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated 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.
    2. Age ≥ 18 at the time of informed consent
    3. Biopsy proven aggressive B-NHL, including DLBCL NOS, follicular lymphoma Grade 3B, Primary Mediastinal B-Cell Lymphoma, T-cell rich B-cell lymphoma, or DLBCL that represents transformation of indolent NHL, (including follicular, marginal zone, and lymphoplasmacytoid lymphoma) excluding chronic lymphocytic leukemia or Hodgkin Lymphoma. Subjects with prior indolent lymphoma must have received therapy after a diagnosis of transformation that is appropriate for aggressive histology as described in 4. The following histologies are not eligible:
    • Lymphoblastic lymphoma
    • Burkitt lymphoma
    • Mantle cell lymphoma
    Any histologies not specifically mentioned must be discussed with the medical monitor. For subjects enrolled in the phase 3 portion of study, pathologic samples will be submitted for central confirmation of disease histology.
    4. Refractory (no prior CMR) or relapsed (prior CMR) following front line treatment of standard multiagent chemotherapy containing an anthracycline AND an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP (14 or 21), R-CHOEP, and DA-R-EOCH. For subjects with refractory disease and who have received radiotherapy, PET positivity should be demonstrated no less than 6 weeks after radiotherapy
    5. Biopsy-proven confirmation of relapsed disease. For subjects with de novo aggressive B-cell lymphoma and primary refractory disease (ie never achieving CMR), biopsy of persistent disease is preferred but persistent PET positivity (ie Deauville ≥ 4) is acceptable at a minimum. For all subjects that have received radiotherapy for DLBCL, PET should be performed no less than 42 days (6 weeks) after the last dose of radiotherapy. For subjects with transformed disease that has been characterized as refractory, rebiopsy (core or excisional biopsy) with demonstration of persistent aggressive B-NHL is required
    6. Received a minimum of 2 cycles of standard of care platinum-based chemotherapy in the S1 setting and had a response of PMD, NMR, PMR as centrally assessed by PET-CT scan or received at least 1 cycle of S1 chemotherapy and had evidence of PD as centrally assessed. A pre-salvage scan is required to be submitted to the central reader if a subject had only 1 cycle of pre-salvage chemotherapy.
    7. Radiographically measurable disease with a clearly demarcated nodal lesion at least 1.5 cm in its largest dimension or a target extranodal lesion at least 1.0 cm in its largest dimension
    8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
    9. Intention to proceed to HDT and autologous HSCT per institutional standards
    10. Laboratory parameters (completed within 14 days prior to enrollment and after the last cycle of S1 chemotherapy):
    Hematology:
    • Absolute neutrophil count (ANC) ≥ 1.0 x 1000000000/L
    • Platelets ≥ 75 x 1000000000/L
    Chemistry:
    • Creatinine clearance ≥ 50 mL/min (calculated using Cockcroft Gault equation)
    • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3X upper limit of normal (ULN)
    • Total bilirubin (TBL) < 2x ULN (unless Gilbert's disease or if liver involvement with lymphoma)
    E.4Principal exclusion criteria
    1. CMR following S1 chemotherapy
    2. Treatment within 30 days prior to randomization with another investigational device or drug study (ies). Other investigational procedures while participating in this study are excluded
    3. Prior anti-CD19-directed therapies
    4. Prior HDT with autologous HSCT
    5. Prior allogeneic HSCT
    6. Presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis
    7. Evidence of CNS involvement by NHL
    8. Known infection with human immunodeficiency virus or chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (anti-hepatitis C virus positive)
    9. History of malignancy other than B-NHL within the past 3 years with the exception of:
    • Malignancy treated with curative intent and with no known active disease present for ≥ 3 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
    • Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ
    10. Subject has known sensitivity to immunoglobulins or any of the products or components to be administered during dosing.
    11. Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator’s knowledge.
    12. 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.
    13. Female subjects who are pregnant or breastfeeding or planning to become pregnant or breastfeed while receiving blinatumomab and for an additional 48 hours after the last dose of blinatumomab. (Females of child bearing potential should only be included after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test.)
    14. Female subjects of childbearing potential unwilling to use an effective method of contraception while receiving blinatumomab and for an additional 48 hours after the last dose of blinatumomab.
    Note: The pregnancy, breastfeeding and contraceptive requirements are specific for blinatumomab. The investigator is responsible for providing the subject (male and female) with pregnancy and breastfeeding (female only) avoidance requirements for other medications given during the study.
    E.5 End points
    E.5.1Primary end point(s)
    Phases 2 and 3:
    • CMR as determined by central radiographic assessment of positron emission tomography-computed tomography (PET-CT) scans using the Lugano Classification
    E.5.1.1Timepoint(s) of evaluation of this end point
    From first subject randomised: 8, 13, 18, 23 months
    E.5.2Secondary end point(s)
    Key Secondary Endpoint:
    Phase 3:
    • OS
    Other Secondary Endpoints:
    Phase 2:
    • ORR
    • PFS
    • Duration of response (DOR)
    • Successful mobilization rate
    • HSCT (both autologous and allogeneic) rates among subjects with post-blinatumomab complete response (CMR) + partial response (PMR)
    • 100-day non-relapse mortality (NRM) after autologous HSCT
    • Blinatumomab concentration steady state, clearance, and half life
    • Incidence and severity of adverse events
    Phase 3:
    • Objective response rate (ORR; CMR+PMR)
    • PFS
    • DOR
    • Successful mobilization rate following protocol assigned therapy
    • HSCT (both autologous and allogeneic) rates among responding subjects (CMR or PMR)
    • 100-day NRM after autologous HSCT rate
    • Patient-reported clinical outcome assessments quality of life (QOLCOA) using the EQ-5D and FACT-Lymphoma tools
    • Blinatumomab steady state concentration and clearance
    • Safety:
    - Overall incidence and severity of treatment-emergent adverse events
    Exploratory Endpoints (Phase 2 and 3):
    • Pharmacodynamics, including descriptive analysis of quantitative and qualitative features of lymphocyte populations and serum or plasma concentrations of cytokines
    • Response rates and duration according to COO designation and c-myc and bcl-2 rearrangement and overexpression, R-IPI, Secondary IPI,
    NCCN IPI, as determined from pretreatment specimens
    • Quantitative analysis of CT-DNA as determined by analysis of tumor-associated mutations in CF CT-DNA from plasma collected at various timepoints before, during, and after treatment
    E.5.2.1Timepoint(s) of evaluation of this end point
    From first subject randomised: 18, 26 months
    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 No
    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) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised No
    E.8.1.2Open No
    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 Yes
    E.8.1.7.1Other trial design description
    A phase 2/3 open label study with randomisation in phase 3 only, against investigators choice
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    In phase 3, Investigator’s Choice from a list in the protocol
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA119
    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
    European Union
    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
    Study completion will occur once 236 death events for phase 3 subjects have occurred or 12 months after the last subject in phase 3 is randomized if 236th death in phase 3 subjects is not observed
    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 months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months4
    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: 166
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 166
    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 state4
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 195
    F.4.2.2In the whole clinical trial 332
    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 Decision2016-09-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-10-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-03-12
    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-Fri Apr 26 00:38:48 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA