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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02393859




Registration number
NCT02393859
Ethics application status
Date submitted
16/03/2015
Date registered
20/03/2015

Titles & IDs
Public title
Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HIgh-Risk (HR) First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)
Scientific title
Phase 3 Trial to Investigate the Efficacy, Safety, and Tolerability of Blinatumomab as Consolidation Therapy Versus Conventional Consolidation Chemotherapy in Pediatric Subjects With HR First Relapse B-precursor ALL
Secondary ID [1] 0 0
2014-002476-92
Secondary ID [2] 0 0
20120215
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia, Acute Lymphoblastic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Blinatumomab
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Vincrisitne
Treatment: Drugs - Daunorubicin
Treatment: Drugs - Methotrexate
Treatment: Drugs - Ifosfamide
Treatment: Drugs - PEG-asparaginase
Treatment: Drugs - Erwinia-asparaginase

Active comparator: High Risk Consolidation 3 (HC3) Chemotherapy - One week of treatment with HC3 followed by 3 weeks of no treatment. The standard intensive consolidation chemotherapy course HC3 includes dexamethasone (10 mg/m\^2/day intravenous \[IV\] on Days 1-6), vincrisitne (1.5 mg/m\^2/day IV on Days 1 and 6), daunorubicin (30 mg/m\^2 IV over 24 hours on Day 5), methotrexate (1 g/m\^2 IV over 36 hours on Day 1), ifosfamide (800 mg/m\^2 IV for 1 hour on Days 2-4), and pegylated \[PEG\]-asparaginase (1000 U/m\^2 IV for 2 hours or intramuscularly \[IM\] on Day 6) or, if allergic, erwinia-asparaginase (20,000 units/m\^2 IV or IM every 48 hours for a total of 6 doses).

Experimental: Blinatumomab - 15 µg/m\^2/day as a continuous intravenous infusion (CIVI) for 4 weeks


Treatment: Drugs: Blinatumomab
15 µg/m\^2/day as a continuous intravenous infusion (CIVI) for 4 weeks

Treatment: Drugs: Dexamethasone
10 mg/m\^2/day intravenous (IV) on Days 1-6

Treatment: Drugs: Vincrisitne
1.5 mg/m\^2/day IV on Days 1 and 6

Treatment: Drugs: Daunorubicin
30 mg/m\^2 IV over 24 hours on Day 5

Treatment: Drugs: Methotrexate
1 g/m\^2 IV over 36 hours on Day 1

Treatment: Drugs: Ifosfamide
800 mg/m\^2 IV for 1 hour on Days 2-4

Treatment: Drugs: PEG-asparaginase
1000 U/m\^2 IV for 2 hours or intramuscularly (IM) on Day 6

Treatment: Drugs: Erwinia-asparaginase
In case of allergic reaction to PEG-asparaginase, participants could change to erwinia-asparaginase, 20,000 units/m2 every 48 hours for a total of 6 doses

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis)
Timepoint [1] 0 0
As of the primary analysis data cutoff date (17 July 2019), overall median follow-up time for EFS was 22.4 months.
Primary outcome [2] 0 0
Kaplan Meier Estimate: EFS (Final Analysis)
Timepoint [2] 0 0
At final analysis, overall median follow-up time for EFS was 51.9 months.
Secondary outcome [1] 0 0
Kaplan Meier Estimate: Overall Survival (OS)
Timepoint [1] 0 0
At final analysis, overall median follow-up time for OS was 55.2 months.
Secondary outcome [2] 0 0
Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation
Timepoint [2] 0 0
Up to End of Treatment (Cycle 1, Day 29)
Secondary outcome [3] 0 0
Cumulative Incidence of Relapse (CIR)
Timepoint [3] 0 0
At final analysis, the overall maximum follow-up time was 82.0 months.
Secondary outcome [4] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs)
Timepoint [4] 0 0
From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.
Secondary outcome [5] 0 0
Number of Participants With TEAEs of Interest
Timepoint [5] 0 0
From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.
Secondary outcome [6] 0 0
Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values
Timepoint [6] 0 0
Up to Day 29 (± 2 days).
Secondary outcome [7] 0 0
Kaplan-Meier Estimate of 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)
Timepoint [7] 0 0
From the date of alloHSCT until death/censor date; median follow up time was 1742.0 days for blinatumomab and 1619.0 days for HC3.
Secondary outcome [8] 0 0
Number of Participants With Anti-Blinatumomab Antibodies Postbaseline (Blinatumomab Arm Only)
Timepoint [8] 0 0
Day 1 to Day 29.
Secondary outcome [9] 0 0
Pharmacokinetics: Concentration at Steady State (Css) (Blinatumomab Arm Only)
Timepoint [9] 0 0
Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15
Secondary outcome [10] 0 0
Pharmacokinetics: Clearance (CL) (Blinatumomab Arm Only)
Timepoint [10] 0 0
Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15

Eligibility
Key inclusion criteria
* Subjects with Philadelphia chromosome negative (Ph-) high-risk (HR) first relapse B-precursor acute lymphoblastic leukemia (ALL; as defined by International Berlin-Frankfurt-Muenster study group/International study for treatment of childhood relapsed ALL [I-BFM SG/IntReALL] criteria)
* Subjects with bone marrow blast percentage < 5% (M1) or bone marrow blast percentage < 25% and =5% (M2) marrow at the time of randomization,
* Age > 28 days and < 18 years at the time of informed consent/assent
* Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated
* Availability of the following material from relapse diagnosis for central analysis of minimal residual disease (MRD) by polymerase chain reaction (PCR): clone-specific primers and reference deoxyribonucleic acid (DNA), as well as primer sequences and analyzed sequences of clonal rearrangements (cases with isolated extramedullary relapse or cases with technical and/or logistic hurdles to obtain and process bone marrow material are exempt from providing this material. In these cases, central MRD analysis only by Flow is permitted).
Minimum age
0 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Clinically relevant central nervous system (CNS) pathology requiring treatment (eg, unstable epilepsy). Evidence of current CNS (CNS 2, CNS 3) involvement by ALL. Subjects with CNS relapse at the time of relapse are eligible if CNS is successfully treated prior to enrollment
* Peripheral neutrophils < 500/µL prior to start of treatment
* Peripheral platelets < 50,000/µL prior to start of treatment
* Currently receiving treatment in another investigational device or drug study or less than 4 weeks since ending treatment on another investigational device or drug study(s), procedures required by IntReALL high-risk (HR) guidelines are allowed
* Chemotherapy related toxicities that have not resolved to = grade 2 (except for parameters defined in Exclusion Criteria 202, 203, 204, and 217)
* 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
* Abnormal renal or hepatic function prior to start of treatment (day 1) as defined below
* Abnormal serum creatinine based on age/gender
* Total bilirubin > 3.0 mg/dL prior to start of treatment (unless related to Gilbert's or Meulengracht disease)
* Documented infection with human immunodeficiency virus (HIV)
* Known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing (excluding asparaginase)
* Post-menarchal female subject who is pregnant or breastfeeding, or is planning to become pregnant or breastfeed while receiving protocol-specified therapy and for at least 12 months after the last dose of chemotherapy
* Post-menarchal female subject who is not willing to practice true sexual abstinence or use a highly effective form of contraception while receiving protocol-specified therapy and for at least 12 months after the last dose of chemotherapy
* Sexually mature male subject who is not willing to practice true sexual abstinence or use a condom with spermicide while receiving protocol-specified therapy and for at least 6 months after last dose of chemotherapy. In countries where spermicide is not available, a condom without spermicide is acceptable
* Sexually mature male subject who is not willing to abstain from sperm donation while receiving protocol-specified therapy and for at least 6 months after last dose of chemotherapy
* 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's and investigator's knowledge
* 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
* Placed into an institution due to juridical or regulatory ruling.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Research Site - Randwick
Recruitment hospital [2] 0 0
Research Site - Westmead
Recruitment hospital [3] 0 0
Research Site - South Brisbane
Recruitment hospital [4] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Austria
State/province [2] 0 0
Graz
Country [3] 0 0
Austria
State/province [3] 0 0
Innsbruck
Country [4] 0 0
Austria
State/province [4] 0 0
Wien
Country [5] 0 0
Belgium
State/province [5] 0 0
Brussels
Country [6] 0 0
Belgium
State/province [6] 0 0
Gent
Country [7] 0 0
Belgium
State/province [7] 0 0
Leuven
Country [8] 0 0
Belgium
State/province [8] 0 0
Liege
Country [9] 0 0
Brazil
State/province [9] 0 0
Paraná
Country [10] 0 0
Brazil
State/province [10] 0 0
Rio Grande Do Sul
Country [11] 0 0
Brazil
State/province [11] 0 0
São Paulo
Country [12] 0 0
Czechia
State/province [12] 0 0
Praha 5
Country [13] 0 0
Denmark
State/province [13] 0 0
Kobenhavn O
Country [14] 0 0
France
State/province [14] 0 0
Bordeaux Cedex
Country [15] 0 0
France
State/province [15] 0 0
Lille
Country [16] 0 0
France
State/province [16] 0 0
Lyon
Country [17] 0 0
France
State/province [17] 0 0
Marseille cedex 5
Country [18] 0 0
France
State/province [18] 0 0
Montpellier cedex 05
Country [19] 0 0
France
State/province [19] 0 0
Nantes cedex 1
Country [20] 0 0
France
State/province [20] 0 0
Paris
Country [21] 0 0
France
State/province [21] 0 0
Strasbourg Cedex
Country [22] 0 0
France
State/province [22] 0 0
Vandoeuvre les Nancy
Country [23] 0 0
Germany
State/province [23] 0 0
Berlin
Country [24] 0 0
Germany
State/province [24] 0 0
Duesseldorf
Country [25] 0 0
Germany
State/province [25] 0 0
Erlangen
Country [26] 0 0
Germany
State/province [26] 0 0
Essen
Country [27] 0 0
Germany
State/province [27] 0 0
Frankfurt am Main
Country [28] 0 0
Germany
State/province [28] 0 0
Freiburg
Country [29] 0 0
Germany
State/province [29] 0 0
Giessen
Country [30] 0 0
Germany
State/province [30] 0 0
Hamburg
Country [31] 0 0
Germany
State/province [31] 0 0
Hannover
Country [32] 0 0
Germany
State/province [32] 0 0
Jena
Country [33] 0 0
Germany
State/province [33] 0 0
Kiel
Country [34] 0 0
Germany
State/province [34] 0 0
München
Country [35] 0 0
Germany
State/province [35] 0 0
Münster
Country [36] 0 0
Germany
State/province [36] 0 0
Tübingen
Country [37] 0 0
Germany
State/province [37] 0 0
Ulm
Country [38] 0 0
Germany
State/province [38] 0 0
Würzburg
Country [39] 0 0
Greece
State/province [39] 0 0
Goudi
Country [40] 0 0
Israel
State/province [40] 0 0
Haifa
Country [41] 0 0
Israel
State/province [41] 0 0
Jerusalem
Country [42] 0 0
Israel
State/province [42] 0 0
Petah Tikva
Country [43] 0 0
Israel
State/province [43] 0 0
Tel Aviv
Country [44] 0 0
Israel
State/province [44] 0 0
Tel Hashomer
Country [45] 0 0
Italy
State/province [45] 0 0
Bologna
Country [46] 0 0
Italy
State/province [46] 0 0
Genova
Country [47] 0 0
Italy
State/province [47] 0 0
Monza (MB)
Country [48] 0 0
Italy
State/province [48] 0 0
Napoli
Country [49] 0 0
Italy
State/province [49] 0 0
Padova
Country [50] 0 0
Italy
State/province [50] 0 0
Pavia
Country [51] 0 0
Italy
State/province [51] 0 0
Roma
Country [52] 0 0
Italy
State/province [52] 0 0
Torino
Country [53] 0 0
Mexico
State/province [53] 0 0
Distrito Federal
Country [54] 0 0
Mexico
State/province [54] 0 0
Jalisco
Country [55] 0 0
Mexico
State/province [55] 0 0
Nuevo León
Country [56] 0 0
Netherlands
State/province [56] 0 0
Rotterdam
Country [57] 0 0
Netherlands
State/province [57] 0 0
Utrecht
Country [58] 0 0
Norway
State/province [58] 0 0
Oslo
Country [59] 0 0
Poland
State/province [59] 0 0
Bydgoszcz
Country [60] 0 0
Poland
State/province [60] 0 0
Krakow
Country [61] 0 0
Poland
State/province [61] 0 0
Lublin
Country [62] 0 0
Poland
State/province [62] 0 0
Wroclaw
Country [63] 0 0
Poland
State/province [63] 0 0
Zabrze
Country [64] 0 0
Portugal
State/province [64] 0 0
Lisboa
Country [65] 0 0
Portugal
State/province [65] 0 0
Porto
Country [66] 0 0
Romania
State/province [66] 0 0
Bucharest
Country [67] 0 0
Romania
State/province [67] 0 0
Cluj-Napoca
Country [68] 0 0
Russian Federation
State/province [68] 0 0
Moscow
Country [69] 0 0
Russian Federation
State/province [69] 0 0
Saint Petersburg
Country [70] 0 0
Spain
State/province [70] 0 0
Andalucía
Country [71] 0 0
Spain
State/province [71] 0 0
Cantabria
Country [72] 0 0
Spain
State/province [72] 0 0
Cataluña
Country [73] 0 0
Spain
State/province [73] 0 0
Comunidad Valenciana
Country [74] 0 0
Spain
State/province [74] 0 0
Galicia
Country [75] 0 0
Spain
State/province [75] 0 0
Madrid
Country [76] 0 0
Spain
State/province [76] 0 0
Murcia
Country [77] 0 0
Sweden
State/province [77] 0 0
Stockholm
Country [78] 0 0
Switzerland
State/province [78] 0 0
Basel
Country [79] 0 0
Switzerland
State/province [79] 0 0
Zuerich
Country [80] 0 0
Turkey
State/province [80] 0 0
Adana
Country [81] 0 0
Turkey
State/province [81] 0 0
Antalya
Country [82] 0 0
Turkey
State/province [82] 0 0
Izmir
Country [83] 0 0
Turkey
State/province [83] 0 0
Kayseri
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Birmingham
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Bristol
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Glasgow
Country [87] 0 0
United Kingdom
State/province [87] 0 0
London
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Manchester
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Newcastle upon Tyne
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Sheffield
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Available to whom?
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.