Leukemia, Acute LymphoblasticPhase 3NCT02393859
Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HIgh-Risk (HR) First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)
A Phase 3 study testing Blinatumomab, Dexamethasone and Vincrisitne in people with Leukemia, Acute Lymphoblastic, run by Amgen at 103 sites in 24 countries.
Trial summary
B-precursor ALL is an aggressive malignant disease. Therapy is usually stratified according to risk characteristics to ensure that appropriate treatment is administered to patients with high-risk of relapse. Read more about this study
- Who is it for?
- Ages 0 to 17 years
- Conditions the study is for
- Leukemia, Acute Lymphoblastic
- What is being tested?
- Blinatumomab, Dexamethasone and Vincrisitne
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 111 participants
- Where
- 103 sitesin 24 countries
- Study dates
- 10 Nov 2015to 21 Nov 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
Who cannot join
- 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
Show all 18Show fewer
- 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.
Trial locations and contacts
103 sites in 24 countries.
103 sites in 24 countries
Germany16 sites
Research Site
Berlin, 13353
Research Site
Düsseldorf, 40225
Research Site
Erlangen, 91054
Research Site
Essen, 45122
Research Site
Frankfurt am Main, 60590
Research Site
Freiburg im Breisgau, 79106
Research Site
Giessen, 35392
Research Site
Hamburg, 20246
Research Site
Hanover, 30625
Research Site
Jena, 07740
Research Site
Kiel, 24105
Research Site
München, 80337
Research Site
Münster, 48149
Research Site
Tübingen, 72076
Research Site
Ulm, 89075
Research Site
Würzburg, 97080
Spain11 sites
Research Site
Barcelona, Catalonia, 08035
Research Site
Barcelona, Catalonia, 08041
Research Site
Boadilla del Monte, Madrid, 28660
Research Site
El Palmar, Murcia, 30120
Research Site
Madrid, 28009
Research Site
Madrid, 28046
Research Site
Málaga, Andalusia, 29011
Research Site
Santander, Cantabria, 39008
Research Site
Santiago de Compostela, Galicia, 15706
Research Site
Seville, Andalusia, 41013
Research Site
Valencia, Valencia, 46026
France10 sites
Research Site
Bordeaux, 33076
Research Site
Lille, 59037
Research Site
Lyon, 69008
Research Site
Marseille, 13385
Research Site
Montpellier, 34295
Research Site
Nantes, 44093
Research Site
Paris, 75012
Research Site
Paris, 75019
Research Site
Strasbourg, 67200
Research Site
Vandœuvre-lès-Nancy, 54511
Italy9 sites
Research Site
Bologna, 40138
Research Site
Genova, 16147
Research Site
Monza (MB), 20900
Research Site
Naples, 80123
Research Site
Padova, 35128
Research Site
Pavia, 27100
Research Site
Roma, 00161
Research Site
Roma, 00165
Research Site
Torino, 10126
United Kingdom8 sites
Research Site
Birmingham, B4 6NH
Research Site
Bristol, BS2 8BJ
Research Site
Glasgow, G51 4TF
Research Site
London, WC1N 3JH
Research Site
Manchester, M13 9WL
Research Site
Newcastle upon Tyne, NE1 4LP
Research Site
Sheffield, S10 2TH
Research Site
Sutton, SM2 5PT
Belgium5 sites
Research Site
Brussels, 1020
Research Site
Brussels, 1200
Research Site
Ghent, 9000
Research Site
Leuven, 3000
Research Site
Liège, 4000
Israel5 sites
Research Site
Haifa, 3109601
Research Site
Jerusalem, 9112001
Research Site
Petah Tikva, 4920235
Research Site
Tel Aviv, 6423906
Research Site
Tel HaShomer, 5262000
Poland5 sites
Research Site
Bydgoszcz, 85-094
Research Site
Krakow, 30-663
Research Site
Lublin, 20-093
Research Site
Wroclaw, 50-556
Research Site
Zabrze, 41-800
Australia4 sites
Research Site
Parkville, Victoria, 3052
Research Site
Randwick, New South Wales, 2031
Research Site
South Brisbane, Queensland, 4101
Research Site
Westmead, New South Wales, 2145
Brazil4 sites
Research Site
Curitba, Paraná, 81520-060
Research Site
Porto Alegre, Rio Grande do Sul, 90035-903
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São Paulo, São Paulo, 04039-001
Research Site
São Paulo, São Paulo, 08270-070
Turkey (Türkiye)4 sites
Research Site
Adana, 01130
Research Site
Antalya, 07059
Research Site
Izmir, 35040
Research Site
Kayseri, 38039
Austria3 sites
Research Site
Graz, 8036
Research Site
Innsbruck, 6020
Research Site
Vienna, 1090
Mexico3 sites
Research Site
Guadalajara, Jalisco, 44340
Research Site
Mexico City, Mexico City, 01120
Research Site
Monterrey, Nuevo León, 64460
Netherlands2 sites
Research Site
Rotterdam, 3015 CN
Research Site
Utrecht, 3584 CS
Romania2 sites
Research Site
Bucharest, 022328
Research Site
Cluj-Napoca, 400177
Russia2 sites
Research Site
Moscow, 115478
Research Site
Saint Petersburg, 197022
Argentina1 site
Research Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, C1199ABB
About this study
Official 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
B-precursor ALL is an aggressive malignant disease. Therapy is usually stratified according to risk characteristics to ensure that appropriate treatment is administered to patients with high-risk of relapse. In general, pediatric treatment regimens are more intense than those employed in adults and include courses of combination chemotherapy. Standard of care chemotherapy is associated with considerable toxicity. There is a lack of novel treatment options for subjects who relapse or are refractory to treatment. Therefore, innovative therapeutic approaches are urgently needed. Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. This study will evaluate the event-free survival (EFS) after treatment with blinatumomab when compared to standard of care (SOC) chemotherapy. The effect of blinatumomab on overall survival and reduction of minimal residual disease compared to SOC chemotherapy will also be investigated.
Read the detailed description
Patients will be randomized in a 1:1 ratio to receive either one cycle of blinatumomab or one block of standard high-risk consolidation chemotherapy. Blinatumomab is administered as a continuous intravenous infusion (CIVI). One cycle of blinatumomab treatment includes 4 weeks of CIVI of blinatumomab. After completing consolidation therapy, the patients should undergo alloHSCT depending on their bone marrow status. The patients will be followed up until the last subject on study is 36 months following alloHSCT or has died, whichever is first.
- Conditions
- Leukemia, Acute Lymphoblastic
- Being tested
- Blinatumomab, Dexamethasone, Vincrisitne, Daunorubicin, Methotrexate
- Keywords
- ALL, High-risk first relapse B-precursor ALL, Precursor Cell Lymphoblastic Leukemia, Neoplasms, Lymphoproliferative Disorders, Immunoproliferative Disorders, Antibodies, Bispecific
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasms, Lymphoproliferative Disorders, Immunoproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BlinatumomabDrug
Also called Blincyto, AMG103
15 μg/m^2/day as a continuous intravenous infusion (CIVI) for 4 weeks
DexamethasoneDrug
10 mg/m^2/day intravenous (IV) on Days 1-6
VincrisitneDrug
1.5 mg/m^2/day IV on Days 1 and 6
DaunorubicinDrug
30 mg/m^2 IV over 24 hours on Day 5
MethotrexateDrug
1 g/m^2 IV over 36 hours on Day 1
IfosfamideDrug
800 mg/m^2 IV for 1 hour on Days 2-4
PEG-asparaginaseDrug
1000 U/m^2 IV for 2 hours or intramuscularly (IM) on Day 6
Erwinia-asparaginaseDrug
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
| Study group | Role | What they receive |
|---|---|---|
| High Risk Consolidation 3 (HC3) Chemotherapy | Active comparator | 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). Receives: Drug: Dexamethasone; Drug: Vincrisitne; Drug: Daunorubicin; Drug: Methotrexate; Drug: Ifosfamide; Drug: PEG-asparaginase; Drug: Erwinia-asparaginase |
| Blinatumomab | Experimental | 15 μg/m^2/day as a continuous intravenous infusion (CIVI) for 4 weeks Receives: Drug: Blinatumomab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis)
EFS is calculated from the time of randomization until the date of relapse or M2 marrow (representative bone marrow aspirate or biopsy with ≥ 5% and < 25% blasts) after having achieved a complete remission (CR), failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. Participants who failed to achieve a CR following treatment with investigational product (IP) or who died before the disease assessment at the end of treatment were considered treatment failures and assigned an EFS duration of 1 day. Participants still alive and event-free were censored on their last disease assessment date.
Participants were said to be in CR when they had the following:
- M1 marrow
- Peripheral blood without blasts
- Absence of extramedullary leukemic involvement
Months are calculated as days from randomization date to event/censor date, divided by 30.5.
Measured: As of the primary analysis data cutoff date (17 July 2019), overall median follow-up time for EFS was 22.4 months.
Kaplan Meier Estimate: EFS (Final Analysis)
EFS is calculated from the time of randomization until the date of relapse or M2 marrow after having achieved a CR, failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. Participants who failed to achieve a CR following treatment with IP or who died before the disease assessment at the end of treatment were considered treatment failures and assigned an EFS duration of 1 day. Participants still alive and event-free were censored on their last disease assessment date.
Participants were said to be in CR when they had the following:
- M1 marrow
- Peripheral blood without blasts
- Absence of extramedullary leukemic involvement
Months are calculated as days from randomization date to event/censor date, divided by 30.5.
Measured: At final analysis, overall median follow-up time for EFS was 51.9 months.
Secondary outcomes (10)
Kaplan Meier Estimate: Overall Survival (OS)
OS was calculated from time of randomization until death due to any cause. Participants still alive were censored at the date they were last known to be alive.
Months were calculated as days from randomization date to event/censor date, divided by 30.5.
Measured: At final analysis, overall median follow-up time for OS was 55.2 months.
Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation
At the end of the first treatment cycle (Day 29) a bone marrow aspiration/biopsy was performed and evaluated by the central MRD laboratory.
MRD response was defined as MRD level < 10^-4, by polymerase chain reaction (PCR) or flow cytometry, at the end of treatment (Cycle 1 Day 29) with study drug. Participants who were part of the MRD Evaluable Set and were missing the end of treatment (Cycle 1 Day 29) assessment for a respective MRD assessment method were considered not to have achieved a response.
Measured: Up to End of Treatment (Cycle 1, Day 29)
Cumulative Incidence of Relapse (CIR)
CIR estimate, presented as median months to relapse, calculated from date of achievement of first CR, using the cumulative incidence method (Fine JP, Gray RJ:1999). Deaths prior to relapse not considered related to an otherwise undocumented relapse were treated as a competing risk. Participants still alive without a date of relapse were censored at the time of last follow-up.
Relapse=presence of ≥1 of the following:
- isolated bone marrow relapse (M3 marrow [representative bone marrow aspirate or biopsy with ≥25% blasts] in the absence of extramedullary involvement)
- combined bone marrow relapse (M2 [representative bone marrow aspirate or biopsy with ≥5% and <25% blasts] or M3 marrow and ≥1 extramedullary manifestation of acute lymphoblastic leukemia)
- central nervous system extramedullary relapse
- testicular extramedullary relapse
- extramedullary relapse at other sites
Months were calculated as days from randomization to event/censor date, divided by 30.5.
Measured: At final analysis, the overall maximum follow-up time was 82.0 months.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs)
Adverse event (AE): any untoward medical occurrence. Serious AE: an AE meeting at least 1 of the following serious criteria: fatal; life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Severity was graded according to the Common Terminology Criteria for AEs (CTCAE) version 4.03: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. Investigational product (IP) in the HC3 arm refers to dexamethasone, methotrexate, daunorubicin, erwinase, ifosfamide, asparaginase, and vincristine, and in the blinatumomab arm refers to blinatumomab. Treatment-related refers to the assessment of a relationship between IP and the event.
Measured: From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.
Number of Participants With TEAEs of Interest
TEAEs of interest included capillary leak syndrome (CLS), cytokine release syndrome (CRS), decreased immunoglobulins (DI), elevated liver enzymes (ELE), embolic and thrombotic events (ETE), infections (INF), infusion reactions without considering duration (IRWCD), medication errors (ME), neurologic events (NE), neutropenia and febrile neutropenia (NFN), pancreatitis (PNC), tumor lysis syndrome, leukoencephalopathy, immunogenicity. Severity was graded according to the CTCAE version 4.03: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death.
Measured: From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.
Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values
Severity was graded according to the CTCAE version 4.03: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. Increases (↑) or decreases (↓) in laboratory value grades (Gr) from baseline (BL) to worst postbaseline (→ PB) grade are presented. NA=not available.
Measured: Up to Day 29 (± 2 days).
Kaplan-Meier Estimate of 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)
The analysis of 100-day mortality after alloHSCT was assessed for participants who received an alloHSCT while in remission and did not receive any additional anti-leukemic treatment. 100-day mortality after alloHSCT was calculated relative to the date of alloHSCT.
The 100-day mortality rate after alloHSCT was defined as the percentage of participants having died up to 100 days after alloHSCT, estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants still alive were censored at the date they were last known to be alive.
Measured: 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.
Number of Participants With Anti-Blinatumomab Antibodies Postbaseline (Blinatumomab Arm Only)
Participants receiving blinatumomab had blood samples analyzed for binding antibodies. Samples testing positive for binding antibodies were also tested for neutralizing antibodies.
Participants who were binding antibody-positive or neutralizing antibody-positive post-baseline with a negative or no result at baseline are presented.
Measured: Day 1 to Day 29.
Pharmacokinetics: Concentration at Steady State (Css) (Blinatumomab Arm Only)
Measured: Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15
Pharmacokinetics: Clearance (CL) (Blinatumomab Arm Only)
Measured: Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2015 (estimated)
- Study start10 Nov 2015
- Primary completion17 Jul 2019
- Study completion21 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Acute LymphoblasticStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 111 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02393859
- Sponsor's protocol ID
- 20120215
- Other IDs
- 2014-002476-92, 2014
- Status last verified
- Jun 2026
- First submitted
- 16 Mar 2015
- Last updated
- 26 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Publications
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.
PubMed 35482538Blinatumomabe 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.
PubMed 33651091Caillon 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.
PubMed 37071263Peters C, Bruno A, Rizzari C, Brescianini A, Von Stackelberg A, Linderkamp C, Zeng Y, Zugmaier G, Locatelli F. Blinatumomab is associated with better post-transplant outcome than chemotherapy in children with high-risk, first-relapse B-cell acute lymphoblastic leukemia irrespective of the conditioning regimen. Haematologica. 2025 Jan 1;110(1):234-238. doi: 10.3324/haematol.2024.285837. No abstract available.
PubMed 39234873Locatelli F, Rizzari C, Gruhn B, Klingebiel T, Parasole R, Linderkamp C, Flotho C, Petit A, Micalizzi C, Eckert C, Moricke A, Sartor M, Hrusak O, Peters C, Saha V, Vinti L, Desai R, Henry M, Zugmaier G, von Stackelberg A. Blinatumomab consolidation in children with high-risk first-relapse B-cell precursor acute lymphoblastic leukemia: final 5-year follow-up analysis of a randomized multicenter phase 3 study. Leukemia. 2026 Jan;40(1):230-234. doi: 10.1038/s41375-025-02800-6. Epub 2025 Nov 13. No abstract available.
PubMed 41233549Diaz Martinez JP, de Maraumont TA, Camacho LM, Garcia L. Cost-effectiveness of blinatumomab for the treatment of B-precursor acute lymphoblastic leukemia pediatric patients with high-risk first-relapse in Mexico. Leuk Res. 2024 Oct;145:107560. doi: 10.1016/j.leukres.2024.107560. Epub 2024 Aug 22.
PubMed 39214018
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02393859
- Acronym / sponsor ID
- 20120215
- Conditions
- Leukemia, Acute Lymphoblastic
- Keywords
- ALL, High-risk first relapse B-precursor ALL, Precursor Cell Lymphoblastic Leukemia, Neoplasms, Lymphoproliferative Disorders, Immunoproliferative Disorders, Antibodies, Bispecific
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 111 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 10 Nov 2015 (actual)
- Primary completion
- 17 Jul 2019 (actual)
- Study completion
- 21 Nov 2022 (actual)
- First posted
- 20 Mar 2015 (estimated)
- Results
- Posted 13 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
B-precursor ALL is an aggressive malignant disease. Therapy is usually stratified according to risk characteristics to ensure that appropriate treatment is administered to patients with high-risk of relapse. In general, pediatric treatment regimens are more intense than those employed in adults and include courses of combination chemotherapy. Standard of care chemotherapy is associated with considerable toxicity. There is a lack of novel treatment options for subjects who relapse or are refractory to treatment. Therefore, innovative therapeutic approaches are urgently needed. Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. This study will evaluate the event-free survival (EFS) after treatment with blinatumomab when compared to standard of care (SOC) chemotherapy. The effect of blinatumomab on overall survival and reduction of minimal residual disease compared to SOC chemotherapy will also be investigated.
Detailed description
Patients will be randomized in a 1:1 ratio to receive either one cycle of blinatumomab or one block of standard high-risk consolidation chemotherapy. Blinatumomab is administered as a continuous intravenous infusion (CIVI). One cycle of blinatumomab treatment includes 4 weeks of CIVI of blinatumomab. After completing consolidation therapy, the patients should undergo alloHSCT depending on their bone marrow status. The patients will be followed up until the last subject on study is 36 months following alloHSCT or has died, whichever is first.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Risk Consolidation 3 (HC3) Chemotherapy | Active comparator | Drug: Dexamethasone, Drug: Vincrisitne, Drug: Daunorubicin, Drug: Methotrexate, Drug: Ifosfamide, Drug: PEG-asparaginase, Drug: Erwinia-asparaginaseOne 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). |
| Blinatumomab | Experimental | Drug: Blinatumomab15 μg/m^2/day as a continuous intravenous infusion (CIVI) for 4 weeks |
Who may qualify
- Ages
- 0 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BlinatumomabAlso: Blincyto, AMG10315 μg/m^2/day as a continuous intravenous infusion (CIVI) for 4 weeks | Drug | Blinatumomab |
| Dexamethasone10 mg/m^2/day intravenous (IV) on Days 1-6 | Drug | High Risk Consolidation 3 (HC3) Chemotherapy |
| Vincrisitne1.5 mg/m^2/day IV on Days 1 and 6 | Drug | High Risk Consolidation 3 (HC3) Chemotherapy |
| Daunorubicin30 mg/m^2 IV over 24 hours on Day 5 | Drug | High Risk Consolidation 3 (HC3) Chemotherapy |
| Methotrexate1 g/m^2 IV over 36 hours on Day 1 | Drug | High Risk Consolidation 3 (HC3) Chemotherapy |
| Ifosfamide800 mg/m^2 IV for 1 hour on Days 2-4 | Drug | High Risk Consolidation 3 (HC3) Chemotherapy |
| PEG-asparaginase1000 U/m^2 IV for 2 hours or intramuscularly (IM) on Day 6 | Drug | High Risk Consolidation 3 (HC3) Chemotherapy |
| Erwinia-asparaginaseIn 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 | Drug | High Risk Consolidation 3 (HC3) Chemotherapy |
Primary outcome
Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis)
Time frame: As of the primary analysis data cutoff date (17 July 2019), overall median follow-up time for EFS was 22.4 months.
EFS is calculated from the time of randomization until the date of relapse or M2 marrow (representative bone marrow aspirate or biopsy with ≥ 5% and < 25% blasts) after having achieved a complete remission (CR), failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. Participants who failed to achieve a CR following treatment with investigational product (IP) or who died before the disease assessment at the end of treatment were considered treatment failures and assigned an EFS duration of 1 day. Participants still alive and event-free were censored on their last disease assessment date. Participants were said to be in CR when they had the following: * M1 marrow * Peripheral blood without blasts * Absence of extramedullary leukemic involvement Months are calculated as days from randomization date to event/censor date, divided by 30.5.
Kaplan Meier Estimate: EFS (Final Analysis)
Time frame: At final analysis, overall median follow-up time for EFS was 51.9 months.
EFS is calculated from the time of randomization until the date of relapse or M2 marrow after having achieved a CR, failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. Participants who failed to achieve a CR following treatment with IP or who died before the disease assessment at the end of treatment were considered treatment failures and assigned an EFS duration of 1 day. Participants still alive and event-free were censored on their last disease assessment date. Participants were said to be in CR when they had the following: * M1 marrow * Peripheral blood without blasts * Absence of extramedullary leukemic involvement Months are calculated as days from randomization date to event/censor date, divided by 30.5.
10 secondary outcomes
Kaplan Meier Estimate: Overall Survival (OS)
Time frame: At final analysis, overall median follow-up time for OS was 55.2 months.
Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation
Time frame: Up to End of Treatment (Cycle 1, Day 29)
Cumulative Incidence of Relapse (CIR)
Time frame: At final analysis, the overall maximum follow-up time was 82.0 months.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs)
Time frame: From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.
Number of Participants With TEAEs of Interest
Time frame: From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.
Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values
Time frame: Up to Day 29 (± 2 days).
Kaplan-Meier Estimate of 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)
Time frame: 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.
Number of Participants With Anti-Blinatumomab Antibodies Postbaseline (Blinatumomab Arm Only)
Time frame: Day 1 to Day 29.
Pharmacokinetics: Concentration at Steady State (Css) (Blinatumomab Arm Only)
Time frame: Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15
Pharmacokinetics: Clearance (CL) (Blinatumomab Arm Only)
Time frame: Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 35482538Locatelli 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.
- BackgroundBlinatumomabe 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
- Background: PubMed 33651091Locatelli 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.
- Background: PubMed 37071263Caillon 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.
- Background: PubMed 39234873Peters C, Bruno A, Rizzari C, Brescianini A, Von Stackelberg A, Linderkamp C, Zeng Y, Zugmaier G, Locatelli F. Blinatumomab is associated with better post-transplant outcome than chemotherapy in children with high-risk, first-relapse B-cell acute lymphoblastic leukemia irrespective of the conditioning regimen. Haematologica. 2025 Jan 1;110(1):234-238. doi: 10.3324/haematol.2024.285837. No abstract available.
- Background: PubMed 41233549Locatelli F, Rizzari C, Gruhn B, Klingebiel T, Parasole R, Linderkamp C, Flotho C, Petit A, Micalizzi C, Eckert C, Moricke A, Sartor M, Hrusak O, Peters C, Saha V, Vinti L, Desai R, Henry M, Zugmaier G, von Stackelberg A. Blinatumomab consolidation in children with high-risk first-relapse B-cell precursor acute lymphoblastic leukemia: final 5-year follow-up analysis of a randomized multicenter phase 3 study. Leukemia. 2026 Jan;40(1):230-234. doi: 10.1038/s41375-025-02800-6. Epub 2025 Nov 13. No abstract available.
- Derived from this study: PubMed 39214018Diaz Martinez JP, de Maraumont TA, Camacho LM, Garcia L. Cost-effectiveness of blinatumomab for the treatment of B-precursor acute lymphoblastic leukemia pediatric patients with high-risk first-relapse in Mexico. Leuk Res. 2024 Oct;145:107560. doi: 10.1016/j.leukres.2024.107560. Epub 2024 Aug 22.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
103 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Blinatumomab, Dexamethasone and Vincrisitne in people with Leukemia, Acute Lymphoblastic, run by Amgen at 103 sites in 24 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 103 sites in Germany, Spain, France, Italy, United Kingdom and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis) (time frame: As of the primary analysis data cutoff date (17 July 2019), overall median follow-up time for EFS was 22.4 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02393859, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2026.