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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02393859
Ethics application status
Date submitted
16/03/2015
Date registered
20/03/2015
Date last updated
12/07/2019

Titles & IDs
Public title
Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HR First Relapse B-precursor 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
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Blinatumomab
Treatment: Drugs - Conventional Consolidation Chemotherapy

Experimental: Blinatumomab - Subjects will be randomized to receive either blinatumomab or standard consolidation chemotherapy.

Active Comparator: Conventional Consolidation Chemotherapy - Subjects will be randomized to receive either blinatumomab or standard consolidation chemotherapy.


Treatment: Drugs: Blinatumomab
The patient will receive one cycle of blinatumomab, which includes 4 weeks of CIVI of blinatumomab.

Treatment: Drugs: Conventional Consolidation Chemotherapy
The patient will receive one block of standard consolidation chemotherapy.

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

Outcomes
Primary outcome [1] 0 0
Event-free survival - Event-free survival (EFS) after blinatumomab when compared to standard of care (SOC) chemotherapy
Timepoint [1] 0 0
Minimum 36 months
Secondary outcome [1] 0 0
Overall survival - Overall survival (OS) of patients treated with blinatumomab when compared to SOC chemotherapy
Timepoint [1] 0 0
Minimum 36 months
Secondary outcome [2] 0 0
MRD response - MRD response, defined as MRD level < 10-4 at the end of treatment with investigational product(s)
Timepoint [2] 0 0
4 weeks
Secondary outcome [3] 0 0
Adverse events - Incidence of adverse events (both serious and non-serious), treatment-related adverse events, adverse events of interest, clinically significant changes in laboratory values
Timepoint [3] 0 0
30 days after the last dose of study treatment or 90 days after alloHSCT (whichever is longer)
Secondary outcome [4] 0 0
Survival - Survival status at 100 days following alloHSCT
Timepoint [4] 0 0
100 days following alloHSCT
Secondary outcome [5] 0 0
Anti-blinatumomab antibody - Incidence of anti-blinatumomab antibody formation (blinatumomab arm only)
Timepoint [5] 0 0
4 weeks
Secondary outcome [6] 0 0
Relapse Incidence - Cumulative incidence of relapse
Timepoint [6] 0 0
Minimum 36 months
Secondary outcome [7] 0 0
Css - Pharmacokinetic (PK) sampling for blinatumomab concentrations for population PK analysis
Timepoint [7] 0 0
2 weeks
Secondary outcome [8] 0 0
Steady-state concentrations - Blinatumomab steady-state concentrations
Timepoint [8] 0 0
2 weeks

Eligibility
Key inclusion criteria
- Subjects with Philadelphia chromosome negative (Ph-) high-risk (HR) first relapse
B-precursor ALL (as defined by I-BFM SG/IntReALL criteria)

- Subjects with M1 or 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
MRD by PCR: clone-specific primers and reference 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
No limit
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Clinically relevant 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

- Abnormal renal or hepatic function prior to start of treatment (day 1) as defined
below: a. Serum creatinine levels above upper limit of normal, based on the normal
ranges for age and gender of the local laboratories. b. Total bilirubin > 3.0 mg/dL
prior to start of treatment (unless related to Gilbert's or Meulengracht disease)

- 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 HR guidelines are allowed

- Chemotherapy related toxicities that have not resolved to = grade 2 (except for
parameters defined in Exclusion Criteria 202, 203, and 204)

- 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

- 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 6 months after the last dose of blinatumomab or for 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 6 months after the last dose of blinatumomab or for 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 thereafter. 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 thereafter

- 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
Recruiting
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
Austria
State/province [1] 0 0
Graz
Country [2] 0 0
Austria
State/province [2] 0 0
Innsbruck
Country [3] 0 0
Austria
State/province [3] 0 0
Wien
Country [4] 0 0
Belgium
State/province [4] 0 0
Brussels
Country [5] 0 0
Belgium
State/province [5] 0 0
Gent
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Belgium
State/province [7] 0 0
Liege
Country [8] 0 0
Brazil
State/province [8] 0 0
São Paulo
Country [9] 0 0
Czechia
State/province [9] 0 0
Praha 5
Country [10] 0 0
Denmark
State/province [10] 0 0
Kobenhavn O
Country [11] 0 0
France
State/province [11] 0 0
Bordeaux Cedex
Country [12] 0 0
France
State/province [12] 0 0
Lille
Country [13] 0 0
France
State/province [13] 0 0
Lyon
Country [14] 0 0
France
State/province [14] 0 0
Marseille cedex 5
Country [15] 0 0
France
State/province [15] 0 0
Montpellier cedex 05
Country [16] 0 0
France
State/province [16] 0 0
Nantes cedex 1
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
France
State/province [18] 0 0
Strasbourg Cedex
Country [19] 0 0
France
State/province [19] 0 0
Vandoeuvre les Nancy
Country [20] 0 0
Germany
State/province [20] 0 0
Berlin
Country [21] 0 0
Germany
State/province [21] 0 0
Duesseldorf
Country [22] 0 0
Germany
State/province [22] 0 0
Erlangen
Country [23] 0 0
Germany
State/province [23] 0 0
Essen
Country [24] 0 0
Germany
State/province [24] 0 0
Frankfurt am Main
Country [25] 0 0
Germany
State/province [25] 0 0
Freiburg
Country [26] 0 0
Germany
State/province [26] 0 0
Giessen
Country [27] 0 0
Germany
State/province [27] 0 0
Hamburg
Country [28] 0 0
Germany
State/province [28] 0 0
Hannover
Country [29] 0 0
Germany
State/province [29] 0 0
Jena
Country [30] 0 0
Germany
State/province [30] 0 0
Kiel
Country [31] 0 0
Germany
State/province [31] 0 0
München
Country [32] 0 0
Germany
State/province [32] 0 0
Münster
Country [33] 0 0
Germany
State/province [33] 0 0
Tübingen
Country [34] 0 0
Germany
State/province [34] 0 0
Ulm
Country [35] 0 0
Germany
State/province [35] 0 0
Würzburg
Country [36] 0 0
Greece
State/province [36] 0 0
Goudi
Country [37] 0 0
Israel
State/province [37] 0 0
Haifa
Country [38] 0 0
Israel
State/province [38] 0 0
Jerusalem
Country [39] 0 0
Israel
State/province [39] 0 0
Petah Tikva
Country [40] 0 0
Israel
State/province [40] 0 0
Tel Aviv
Country [41] 0 0
Israel
State/province [41] 0 0
Tel Hashomer
Country [42] 0 0
Italy
State/province [42] 0 0
Bologna
Country [43] 0 0
Italy
State/province [43] 0 0
Genova
Country [44] 0 0
Italy
State/province [44] 0 0
Monza (MB)
Country [45] 0 0
Italy
State/province [45] 0 0
Napoli
Country [46] 0 0
Italy
State/province [46] 0 0
Padova
Country [47] 0 0
Italy
State/province [47] 0 0
Pavia
Country [48] 0 0
Italy
State/province [48] 0 0
Roma
Country [49] 0 0
Italy
State/province [49] 0 0
Torino
Country [50] 0 0
Mexico
State/province [50] 0 0
Distrito Federal
Country [51] 0 0
Mexico
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Nuevo León
Country [52] 0 0
Netherlands
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Rotterdam
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Netherlands
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Utrecht
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Poland
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Bydgoszcz
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Poland
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Krakow
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Poland
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Lublin
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Wroclaw
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Zabrze
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Portugal
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Lisboa
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Portugal
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Porto
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Russian Federation
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Moscow
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Russian Federation
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Saint Petersburg
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Spain
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Andalucía
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Spain
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Cantabria
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Spain
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Cataluña
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Spain
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Comunidad Valenciana
Country [67] 0 0
Spain
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Galicia
Country [68] 0 0
Spain
State/province [68] 0 0
Madrid
Country [69] 0 0
Spain
State/province [69] 0 0
Murcia
Country [70] 0 0
Sweden
State/province [70] 0 0
Stockholm
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Switzerland
State/province [71] 0 0
Basel
Country [72] 0 0
Switzerland
State/province [72] 0 0
Zuerich
Country [73] 0 0
Turkey
State/province [73] 0 0
Adana
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Turkey
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Antalya
Country [75] 0 0
Turkey
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Izmir
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Turkey
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Kayseri
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Birmingham
Country [78] 0 0
United Kingdom
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Bristol
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United Kingdom
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Glasgow
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
State/province [82] 0 0
Newcastle upon Tyne
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Sheffield
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Sutton

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

Ethics approval
Ethics application status

Summary
Brief 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. 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.
Trial website
https://clinicaltrials.gov/show/NCT02393859
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
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02393859