Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HIgh-Risk (HR) First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)
NCT ID: NCT02393859
Last Updated: 2024-05-29
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
111 participants
INTERVENTIONAL
2015-11-10
2022-11-21
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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).
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
PEG-asparaginase
1000 U/m\^2 IV for 2 hours or intramuscularly (IM) on Day 6
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
Blinatumomab
15 μg/m\^2/day as a continuous intravenous infusion (CIVI) for 4 weeks
Blinatumomab
15 μg/m\^2/day as a continuous intravenous infusion (CIVI) for 4 weeks
Interventions
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Blinatumomab
15 μg/m\^2/day as a continuous intravenous infusion (CIVI) for 4 weeks
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
PEG-asparaginase
1000 U/m\^2 IV for 2 hours or intramuscularly (IM) on Day 6
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
Other Intervention Names
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Eligibility Criteria
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Inclusion 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).
Exclusion Criteria
* 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
* 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.
0 Years
17 Years
ALL
No
Sponsors
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Amgen
INDUSTRY
Responsible Party
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Principal Investigators
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MD
Role: STUDY_DIRECTOR
Amgen
Locations
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Research Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
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Randwick, New South Wales, Australia
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Westmead, New South Wales, Australia
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South Brisbane, Queensland, Australia
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Parkville, Victoria, Australia
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Graz, , Austria
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Innsbruck, , Austria
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Vienna, , Austria
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Brussels, , Belgium
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Brussels, , Belgium
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Ghent, , Belgium
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Leuven, , Belgium
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Liège, , Belgium
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Curitba, Paraná, Brazil
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Porto Alegre, Rio Grande do Sul, Brazil
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São Paulo, São Paulo, Brazil
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São Paulo, São Paulo, Brazil
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Prague, , Czechia
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København Ø, , Denmark
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Bordeaux, , France
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Lille, , France
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Lyon, , France
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Marseille, , France
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Montpellier, , France
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Nantes, , France
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Paris, , France
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Paris, , France
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Strasbourg, , France
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Vandœuvre-lès-Nancy, , France
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Berlin, , Germany
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Düsseldorf, , Germany
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Erlangen, , Germany
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Essen, , Germany
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Frankfurt am Main, , Germany
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Freiburg im Breisgau, , Germany
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Giessen, , Germany
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Hamburg, , Germany
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Hanover, , Germany
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Jena, , Germany
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Kiel, , Germany
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München, , Germany
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Münster, , Germany
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Tübingen, , Germany
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Ulm, , Germany
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Würzburg, , Germany
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Goudi, , Greece
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Haifa, , Israel
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Jerusalem, , Israel
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Petah Tikva, , Israel
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Tel Aviv, , Israel
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Tel Litwinsky, , Israel
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Bologna, , Italy
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Genova, , Italy
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Monza (MB), , Italy
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Napoli, , Italy
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Padua, , Italy
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Pavia, , Italy
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Roma, , Italy
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Roma, , Italy
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Torino, , Italy
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Guadalajara, Jalisco, Mexico
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Mexico City, Mexico City, Mexico
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Monterrey, Nuevo León, Mexico
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Rotterdam, , Netherlands
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Utrecht, , Netherlands
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Oslo, , Norway
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Bydgoszcz, , Poland
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Krakow, , Poland
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Lublin, , Poland
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Wroclaw, , Poland
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Zabrze, , Poland
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Lisbon, , Portugal
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Porto, , Portugal
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Bucharest, , Romania
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Cluj-Napoca, , Romania
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Moscow, , Russia
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Saint Petersburg, , Russia
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Málaga, Andalusia, Spain
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Seville, Andalusia, Spain
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Santander, Cantabria, Spain
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Barcelona, Catalonia, Spain
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Barcelona, Catalonia, Spain
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Santiago de Compostela, Galicia, Spain
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Boadilla del Monte, Madrid, Spain
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El Palmar, Murcia, Spain
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Valencia, Valencia, Spain
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Madrid, , Spain
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Madrid, , Spain
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Stockholm, , Sweden
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Basel, , Switzerland
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Zurich, , Switzerland
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Adana, , Turkey (Türkiye)
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Antalya, , Turkey (Türkiye)
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Izmir, , Turkey (Türkiye)
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Kayseri, , Turkey (Türkiye)
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Birmingham, , United Kingdom
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Bristol, , United Kingdom
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Glasgow, , United Kingdom
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London, , United Kingdom
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Manchester, , United Kingdom
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Newcastle upon Tyne, , United Kingdom
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Sheffield, , United Kingdom
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Sutton, , United Kingdom
Countries
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References
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Locatelli F, Eckert C, Hrusak O, Buldini B, Sartor M, Zugmaier G, Zeng Y, Pilankar D, Morris J, von Stackelberg A. Blinatumomab overcomes poor prognostic impact of measurable residual disease in pediatric high-risk first relapse B-cell precursor acute lymphoblastic leukemia. Pediatr Blood Cancer. 2022 Aug;69(8):e29715. doi: 10.1002/pbc.29715. Epub 2022 Apr 28.
Blinatumomabe em pacientes pediátricos com leucemia linfoblástica aguda B em primeira recidiva de alto risco: um estudo de custo-efetividade. van Beurden-Tan CHY, Ribeiro RA, Seber A, de Martino Lee ML, Marçola M, Schuetz R, Loggetto SR, Maiolino A. Jornal Brasileiro de Economia da Saúde 14(1): 41-50. 10.21115/JBES.v14.n1.p41-50
Locatelli F, Zugmaier G, Rizzari C, Morris JD, Gruhn B, Klingebiel T, Parasole R, Linderkamp C, Flotho C, Petit A, Micalizzi C, Mergen N, Mohammad A, Kormany WN, Eckert C, Moricke A, Sartor M, Hrusak O, Peters C, Saha V, Vinti L, von Stackelberg A. Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):843-854. doi: 10.1001/jama.2021.0987.
Caillon M, Brethon B, van Beurden-Tan C, Supiot R, Le Mezo A, Chauny JV, Majer I, Petit A. Cost-Effectiveness of Blinatumomab in Pediatric Patients with High-Risk First-Relapse B-Cell Precursor Acute Lymphoblastic Leukemia in France. Pharmacoecon Open. 2023 Jul;7(4):639-653. doi: 10.1007/s41669-023-00411-4. Epub 2023 Apr 18.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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AmgenTrials clinical trials website
Other Identifiers
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2014-002476-92
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
20120215
Identifier Type: -
Identifier Source: org_study_id
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