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   43871   clinical trials with a EudraCT protocol, of which   7290   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:2019-004780-52
    Sponsor's Protocol Code Number:20180257
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2020-06-10
    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 ConcernedAustria - BASG
    A.2EudraCT number2019-004780-52
    A.3Full title of the trial
    A Phase 1/2 Open-label Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of adults with Relapsed or Refractory B cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase 1/2 study of subcutaneous blinatumomab administration in adults with R/R B-ALL
    A.4.1Sponsor's protocol code number20180257
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04521231
    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
    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 GmbH
    B.5.2Functional name of contact pointMedical Information
    B.5.3 Address:
    B.5.3.1Street AddressFranz-Josefs-Kai 47
    B.5.3.2Town/ cityWien
    B.5.3.3Post code1010
    B.5.3.4CountryAustria
    B.5.4Telephone number+43150217
    B.5.5Fax number+4315021720
    B.5.6E-mailmedinfo-at@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 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
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous 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 mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.0
    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
    Adults with relapsed or refractory B-precursor ALL (R/R B-ALL)
    E.1.1.1Medical condition in easily understood language
    Acute Lymphoblastic Leukemia – a cancer of the blood and marrow
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10000844
    E.1.2Term Acute lymphoblastic leukaemia
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10063621
    E.1.2Term Acute lymphoblastic leukaemia 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
    Dose Escalation
    -Evaluate the safety and tolerability of subcutaneous (SC) blinatumomab for treatment of Relapsed or Refractory B cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL)
    -Determine the maximum tolerated dose (MTD) and preliminary recommended phase 2 dose(s)(RP2D) of SC administered blinatumomab
    Dose Expansion
    -Evaluate the efficacy of SC blinatumomab
    E.2.2Secondary objectives of the trial
    Dose Escalation
    -Determine pharmacokinetics (PK) following SC blinatumomab
    -Evaluate the efficacy of SC blinatumomab
    -Evaluate the immunogenicity of SC blinatumomab
    Dose Expansion
    -Determine PK following SC blinatumomab
    -Evaluate the immunogenicity of SC blinatumomab
    -Evaluate the relapse-free survival (RFS) induced by SC blinatumomab
    -Evaluate the effect of SC blinatumomab on overall survival
    -Evaluate the effect of SC blinatumomab on the duration of complete response
    -Evaluate the effect of SC blinatumomab on the duration of minimal/measurable residual disease (MRD) response
    -Evaluate the safety and tolerability of SC blinatumomab
    -Evaluate patient-reported outcomes and quality of life outcomes with SC blinatumomab
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    101 Subject has provided informed consent prior to initiation of any study specific activities/procedures and/or the 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.
    102 Age ≥ 18 years at time of informed consent
    For disease status: subjects in dose escalation and dose expansion (cohorts Ph2a1 to Ph2a4) must fulfill at least 1 of inclusion criteria 103, 104, or 105 for eligibility.
    Cohort Ph2b only:Subjects will be eligible if they have B-ALL and meet the MRD criteria defined in inclusion criterion #109 below. Subjects with R/R B-ALL in CR (<5% BMB) who meet criteria for MRD will be eligible for cohort Ph2b. With the exception of disease status criteria (ie, inclusion criteria #103, #104, #105, #106), Ph2b cohort subjects must satisfy all other inclusion criteria to be eligible.
    103 Subjects with B-precursor ALL with any of the following:
    •Either Refractory (to primary induction) therapy or refractory to at least 1 salvage therapy OR
    • In untreated first, second, third or greater relapse or refractory relapse:
    - First Relapse is defined achievement of first CR (CR1) during upfront therapy then relapse during or after continuation therapy
    - Primary Refractory disease is defined as the absence of CR after standard induction therapy.
    - Refractory relapse is defined as lack of CR after salvage treatment
    - Second relapse or later relapse is defined as relapse after achieving a second CR (CR2) in first or later salvage
    - Refractory to salvage is defined as no attainment of CR after salvage
    104 Relapsed or Refractory at any time after first salvage therapy
    105 Relapse at any time after allogenic HSCT.
    106 Greater than or equal to 5% blasts in the BM
    107 Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
    108 Subjects with relapse or refractory B Cell ALL Ph+ disease and that are intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
    109 For subjects in the dose expansion MRD cohort only (cohort Ph2b), BMB must be <5% and ≥0.1%. This will replace inclusion criterion #106 for subjects in this cohort
    E.4Principal exclusion criteria
    Disease Related
    - Active ALL in the CNS. Presence of > 5 white blood cells (WBC) per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present (confirmed by CSF analysis) and or clinical signs of CNS leukemia. If CSF leukemia is present subjects will have to receive intrathecal therapy and have documented negative CSF prior to enrolling.
    Other Medical Conditions
    - 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.
    - Isolated extramedullary (EM) disease.
    - Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
    - Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication.
    - Known hypersensitivity to blinatumomab or to any component of the product formulation.
    - Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus.
    - Symptoms and/or clinical signs and/or radiological and/or sonographic signs that indicate an acute or uncontrolled chronic infection, any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol.
    - Testicular leukemia.
    - History of malignancy other than ALL within 3 years prior to start of protocol-specified therapy except for:
    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.
    Prior/Concomitant Therapy
    - Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy
    - Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy. With the exception of intrathecal chemotherapy and/or low dose maintenance therapy for example vinca alkaloids, mercaptopurine, methotrexate, or hydroxyurea (any low dose chemotherapy as stated above must be discontinued before starting pre-phase) or pre-phase chemotherapy and/or dexamethasone.
    - Immunotherapy (eg, rituximab, alemtuzumab) within 4 weeks before start of protocol-specified therapy. Prior failed CD19 directed therapy such as prior blinatumomab or CD19 CAR T cells will be allowed (with demonstrated continued CD19+ expression), if treatment ended > 4 weeks prior to start of protocol therapy.
    Prior/Concurrent Clinical Study Experience
    - 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(ies). Other investigational studies are not permitted while participating in this study.
    Diagnostic Assessments
    - Abnormal screening laboratory values as defined below:
    Total bilirubin >3.0 mg/dL prior to start of treatment (unless related to Gilbert’s or Meulengracht disease)
    Estimated Creatinine clearance < 60 mL/min
    Other Exclusions
    - Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 96 hours after the last dose of protocol-specified therapy.
    - Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 96 hours after the last dose of protocol-specified therapy.
    - Female subjects of childbearing potential with a positive pregnancy test assessed during Screening by a serum pregnancy test and/or urine pregnancy test.
    - 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 awareness
    E.5 End points
    E.5.1Primary end point(s)
    Dose Escalation
    • Dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAE), serious TEAE, treatment-related TEAE, and adverse events.
    Dose Expansion
    • CR/CRh within the first 2 cycles for Ph2a (R/R B-ALL) and CR with MRD < 0.01% within the first 2 cycles for Ph2b (MRD B-ALL)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Dose escalation
    Unless otherwise specified, statistical analyses of safety endpoints will be done using subjects from the safety analysis set.
    Subject incidence of DLT will be tabulated overall and by planned cohort.
    Safety data will be reviewed on an ongoing basis.
    Dose expansion
    The proportion of subjects with a response to treatment (CR/CRh for Ph2a and CR with MRD <0.01% for Ph2b) and 95% CI will be tabulated overall and by cohort.
    E.5.2Secondary end point(s)
    Dose Escalation
    • Blinatumomab PK parameters following SC administration including, but not limited to, minimum concentration over the dosing interval (Ctrough), maximum concentration (Cmax), time to maximum concentration (Tmax), area under the concentration-time curve (AUC)
    • Complete remission/complete remission with partial hematological recovery/(CR/CRh) within the first 2 cycles
    • Anti-blinatumomab antibody formation
    Dose Expansion
    • Blinatumomab PK parameters following SC administration including, but not limited to Cmin, Cmax, Tmax, area under the concentration time and AUC
    • Anti-blinatumomab antibody formation
    • RFS in subjects who achieve response (CR/CRh within the first 2 cycles for Ph2a and CR with MRD<0.01% within the first 2 cycles for Ph2b) is defined as the time from the first achievement of this response until date of the first relapse including extramedullary relapse, or death due to any cause, whichever occurs first
    • Overall survival is calculated from the time of the start of first dose of SC blinatumomab until death due to any cause
    • Duration of complete response is defined as the time from the first onset of response (CR/CRh within the first 2 cycles for Ph2a and CR with MRD <0.01% within the first 2 cycles for Ph2b) until the relapse including extramedullary relapse.
    • Duration of MRD response is defined as the time from the first onset of MRD response until MRD relapse
    • TEAEs, serious TEAEs, treatment related TEAEs, and adverse events
    • Summary scores at each assessment and change from baseline as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ C30)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Dose escalation
    The proportion of subjects with a response to treatment(CR,CRh)and 95%CI will be tabulated overall and by dose level.
    Dose expansion
    Summaries of secondary efficacy endpoints of OS,RFS,duration of complete response,duration of MRD response will be reported overall and by cohort.
    Analysis for RFS and duration of complete response will be performed for subjects with response(CR/CRh within the first 2cycles for Ph2a and CRwith MRD<0.01% within the first 2cycles for Ph2b).Number of subjects with events,number of subjects censored,KM estimates at select time points,KM quartiles(when estimable)and their 95%CI,and KMcurves will be provided for OS,RFS,duration of response,and duration of MRD response.
    Subject incidence of DLT will be tabulated overall and by planned cohort.
    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 No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    dose-finding study to investigate the PK, safety, and clinical activity of escalating dose levels
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA22
    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
    Canada
    Japan
    United States
    Austria
    France
    Netherlands
    Spain
    Germany
    Italy
    Turkey
    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
    The date when the last subject is assessed or receives an intervention for the final collection of data for the primary endpoint(s), for the purposes of conducting the final analysis, whether the study concluded as planned in the protocol or was terminated early.
    The date when the last subject across all sites is assessed or receives an intervention for evaluation in the study (LSLV), following any additional parts in the study (eg,additional antibody testing long-term follow-up),as applicable.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months6
    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: 107
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    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 state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 130
    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)
    N/A
    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 Decision2020-06-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-06-25
    P. End of Trial
    P.End of Trial StatusCompleted
    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-Sun May 05 01:34:12 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA