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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03643276




Registration number
NCT03643276
Ethics application status
Date submitted
12/07/2018
Date registered
22/08/2018
Date last updated
2/01/2020

Titles & IDs
Public title
Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017
Scientific title
International Collaborative Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017
Secondary ID [1] 0 0
AIEOP-BFM ALL 2017
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia, Pediatric 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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Blinatumomab
Treatment: Drugs - Bortezomib
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin
Treatment: Drugs - DAUNOrubicin Liposomal Injection [DaunoXome]
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Etoposide
Treatment: Drugs - Fludarabine Phosphate
Treatment: Drugs - Ifosfamide
Treatment: Drugs - 6-Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Pegaspargase
Treatment: Drugs - Prednisolone
Treatment: Drugs - Tioguanin
Treatment: Drugs - Vincristine
Treatment: Drugs - Vindesine
Treatment: Drugs - Erwinase

Active Comparator: pB: early (non-)HR-standard/MR-standard - Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.

Experimental: pB: early HR-exp./MR-standard - Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.

Experimental: pB: early (non)HR-standard/MR-exp. - Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.

Experimental: pB: early HR-exp./MR-exp. - Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.

Active Comparator: pB: early (non-)HR-standard/HR-standard - Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive DNX-FLA (liposomal daunorubicin, fludarabine, HD-cytarabine, IT-MTX).

Experimental: pB: early HR-exp./HR-standard - Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive DNX-FLA (liposomal daunorubicin, fludarabine, HD-cytarabine, IT-MTX)

Experimental: pB: early (non-)HR-standard/HR-exp. - Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive DNX-FLA (liposomal daunorubicin, fludarabine, HD-cytarabine, IT-MTX)

Experimental: pB: early HR-exp./HR-exp. - Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive DNX-FLA (liposomal daunorubicin, fludarabine, HD-cytarabine, IT-MTX)

Other: pB: early non-HR/SR - Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.

Active Comparator: T: early non-SR-standard/(non-)HR - Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive DNX-FLA (liposomal daunorubicin, fludarabine, HD-cytarabine, IT-MTX)

Experimental: T: early non-SR-exp/(non-)HR - Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive DNX-FLA (liposomal daunorubicin, fludarabine, HD-cytarabine, IT-MTX)

Other: T: early SR/non-HR - Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.


Treatment: Drugs: Blinatumomab
Experimental therapy in randomizations R-HR and R-MR

Treatment: Drugs: Bortezomib
Experimental therapy in randomization R-eHR

Treatment: Drugs: Cyclophosphamide
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T

Treatment: Drugs: Cytarabine
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block DNX-FLA for patients with very high relapse risk

Treatment: Drugs: Daunorubicin
Part of standard chemotherapy

Treatment: Drugs: DAUNOrubicin Liposomal Injection [DaunoXome]
Part of intensification block DNX-FLA for patients with very high relapse risk

Treatment: Drugs: Dexamethasone
Part of standard chemotherapy

Treatment: Drugs: Doxorubicin
Part of standard chemotherapy

Treatment: Drugs: Etoposide
Part of standard chemotherapy

Treatment: Drugs: Fludarabine Phosphate
Part of intensification block DNX-FLA for patients with very high relapse risk

Treatment: Drugs: Ifosfamide
Part of standard chemotherapy

Treatment: Drugs: 6-Mercaptopurine
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T

Treatment: Drugs: Methotrexate
Part of standard chemotherapy

Treatment: Drugs: Pegaspargase
Part of standard chemotherapy

Treatment: Drugs: Prednisolone
Part of standard chemotherapy

Treatment: Drugs: Tioguanin
Part of standard chemotherapy

Treatment: Drugs: Vincristine
Part of standard chemotherapy

Treatment: Drugs: Vindesine
Part of standard chemotherapy

Treatment: Drugs: Erwinase
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction

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

Outcomes
Primary outcome [1] 0 0
Event-free survival - Randomization R-eHR, R-HR and R-T: Time from randomization until the first event defined as follow: cytomorphological or molecular non-response (resistance to protocol treatment, considered as event at day zero), relapse, second malignancy or death from any cause. This will be called EFS time.
Timepoint [1] 0 0
Assessed up to 120 months from start of study
Primary outcome [2] 0 0
Disease-free survival - Randomization R-MR: Time from randomization until the first event defined as follow: Relapse, second malignancy or death from any cause. This will be called DFS time.
Timepoint [2] 0 0
Assessed up to 120 months from start of study
Secondary outcome [1] 0 0
Survival - All patients/randomizations: Time until death from any cause, starting at the same time point as the EFS/DFS.
Timepoint [1] 0 0
Assessed up to 120 months from start of study
Secondary outcome [2] 0 0
Treatment-related mortality - Frequency and incidence of treatment-related mortality in induction or continuous complete remission
Timepoint [2] 0 0
Assessed up to 120 months from start of study
Secondary outcome [3] 0 0
Adverse Events of interest/Serious Adverse Events - Frequency and incidence of adverse events of interest and serious adverse events in specific protocol phases, randomized arms and overall during follow-up
Timepoint [3] 0 0
Assessed up to 120 months from start of study
Secondary outcome [4] 0 0
MRD response - MRD load after the randomized treatment phases (R-eHR, R-HR, R-MR and R-T) as well as after the first/second cycle of Blinatumomab or after the HR 2'/HR 3' block (R-HR)
Timepoint [4] 0 0
Measurements of MRD response at end of randomized treatments (intended time frame 13 weeks in R-eHR/R-T, 26 weeks in R-HR, 34 weeks in R-MR).
Secondary outcome [5] 0 0
Proportion of patients with Blina Poor-Response - Proportion of patients with poor MRD response to the first Blinatumomab cycle ("Blinatumomab Poor-Response") (R-HR)
Timepoint [5] 0 0
Measurements of MRD response intended after 30 weeks from individual start of treatment, assessment of proportion at 120 months from start of study

Eligibility
Key inclusion criteria
- newly diagnosed acute lymphoblastic leukemia or

- newly diagnosed mixed phenotype acute leukemia (MPAL) meeting one of the following
criteria:

- biphenotypic with a dominant T or B lineage assignment

- bilineal either with a dominant lymphoblastic population or if another reasonable
rationale exists to treat the patient with an ALL-based therapy regimen

- newly diagnosed acute undifferentiated leukemia

- age < 18 years (up to 17 years and 365 days) at the day of diagnosis

- patient enrolled in a participating center

- written informed consent to trial participation and transfer and processing of data A
subsequent removal from the study is only allowed if the inclusion criteria turn out
not to be fulfilled or in the case of pregnancy of the patient.
Minimum age
No limit
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Ph+ (BCR-ABL1 or t(9;22)-positive) ALL

- bilineal leukemia with a lymphoblastic and a separate non-lymphoblastic (= 10% of
total cells) blast subset

- pre-treatment with cytostatic drugs

- glucocorticoid pre-treatment with = 1 mg/kg/d for more than two weeks during the last
month before diagnosis

- treatment started according to another protocol

- underlying disease that does not allow treatment according to the protocol (e.g.
severe congenital heart disease, Charcot-Marie Syndrome, Ataxia-teleangiectasia…)

- ALL diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy

- evidence of pregnancy or lactation period

- Sexually active adolescents not willing to use highly effective contraceptive method
(pearl index <1) until 12 months after end of anti-leukemic therapy

- participation in another clinical trial except for add-on trials within the scope of
supportive care approved by the sponsor

- live vaccine immunization within 2 weeks before start of protocol treatment

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
Factorial
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)
Recruitment hospital [1] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [2] 0 0
Perth Children's Hospital - Nedlands
Recruitment hospital [3] 0 0
John Hunter Children's Hospital - New Lambton Heights
Recruitment hospital [4] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [5] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
- Hobart
Recruitment postcode(s) [2] 0 0
- Nedlands
Recruitment postcode(s) [3] 0 0
- New Lambton Heights
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment postcode(s) [5] 0 0
- Westmead
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
Linz
Country [4] 0 0
Austria
State/province [4] 0 0
Salzburg
Country [5] 0 0
Austria
State/province [5] 0 0
Vienna
Country [6] 0 0
Czechia
State/province [6] 0 0
Brno
Country [7] 0 0
Czechia
State/province [7] 0 0
Hradec Králové
Country [8] 0 0
Czechia
State/province [8] 0 0
Olomouc
Country [9] 0 0
Czechia
State/province [9] 0 0
Ostrava-Poruba
Country [10] 0 0
Czechia
State/province [10] 0 0
Plzen
Country [11] 0 0
Czechia
State/province [11] 0 0
Praha
Country [12] 0 0
Czechia
State/province [12] 0 0
Ústí nad Labem
Country [13] 0 0
Czechia
State/province [13] 0 0
Ceské Budejovice
Country [14] 0 0
Germany
State/province [14] 0 0
Aachen
Country [15] 0 0
Germany
State/province [15] 0 0
Augsburg
Country [16] 0 0
Germany
State/province [16] 0 0
Berlin
Country [17] 0 0
Germany
State/province [17] 0 0
Braunschweig
Country [18] 0 0
Germany
State/province [18] 0 0
Chemnitz
Country [19] 0 0
Germany
State/province [19] 0 0
Cottbus
Country [20] 0 0
Germany
State/province [20] 0 0
Datteln
Country [21] 0 0
Germany
State/province [21] 0 0
Dortmund
Country [22] 0 0
Germany
State/province [22] 0 0
Dresden
Country [23] 0 0
Germany
State/province [23] 0 0
Düsseldorf
Country [24] 0 0
Germany
State/province [24] 0 0
Erfurt
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
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
Greifswald
Country [31] 0 0
Germany
State/province [31] 0 0
Göttingen
Country [32] 0 0
Germany
State/province [32] 0 0
Hannover
Country [33] 0 0
Germany
State/province [33] 0 0
Heidelberg
Country [34] 0 0
Germany
State/province [34] 0 0
Heilbronn
Country [35] 0 0
Germany
State/province [35] 0 0
Herdecke
Country [36] 0 0
Germany
State/province [36] 0 0
Homburg
Country [37] 0 0
Germany
State/province [37] 0 0
Jena
Country [38] 0 0
Germany
State/province [38] 0 0
Karlsruhe
Country [39] 0 0
Germany
State/province [39] 0 0
Kassel
Country [40] 0 0
Germany
State/province [40] 0 0
Kiel
Country [41] 0 0
Germany
State/province [41] 0 0
Köln
Country [42] 0 0
Germany
State/province [42] 0 0
Leipzig
Country [43] 0 0
Germany
State/province [43] 0 0
Lübeck
Country [44] 0 0
Germany
State/province [44] 0 0
Magdeburg
Country [45] 0 0
Germany
State/province [45] 0 0
Mannheim
Country [46] 0 0
Germany
State/province [46] 0 0
Minden
Country [47] 0 0
Germany
State/province [47] 0 0
München
Country [48] 0 0
Germany
State/province [48] 0 0
Münster
Country [49] 0 0
Germany
State/province [49] 0 0
Nürnberg
Country [50] 0 0
Germany
State/province [50] 0 0
Oldenburg
Country [51] 0 0
Germany
State/province [51] 0 0
Regensburg
Country [52] 0 0
Germany
State/province [52] 0 0
Rostock
Country [53] 0 0
Germany
State/province [53] 0 0
Sankt Augustin
Country [54] 0 0
Germany
State/province [54] 0 0
Schwerin
Country [55] 0 0
Germany
State/province [55] 0 0
Stuttgart
Country [56] 0 0
Germany
State/province [56] 0 0
Trier
Country [57] 0 0
Germany
State/province [57] 0 0
Tuebingen
Country [58] 0 0
Germany
State/province [58] 0 0
Ulm
Country [59] 0 0
Germany
State/province [59] 0 0
Wolfsburg
Country [60] 0 0
Germany
State/province [60] 0 0
Wuerzburg
Country [61] 0 0
Israel
State/province [61] 0 0
Beer Sheva
Country [62] 0 0
Israel
State/province [62] 0 0
Haifa
Country [63] 0 0
Israel
State/province [63] 0 0
Jerusalem
Country [64] 0 0
Israel
State/province [64] 0 0
Petach-Tikva
Country [65] 0 0
Israel
State/province [65] 0 0
Ramat Gan
Country [66] 0 0
Israel
State/province [66] 0 0
Tel-Aviv
Country [67] 0 0
Italy
State/province [67] 0 0
Ancona
Country [68] 0 0
Italy
State/province [68] 0 0
Bari
Country [69] 0 0
Italy
State/province [69] 0 0
Bergamo
Country [70] 0 0
Italy
State/province [70] 0 0
Bologna
Country [71] 0 0
Italy
State/province [71] 0 0
Brescia
Country [72] 0 0
Italy
State/province [72] 0 0
Cagliari
Country [73] 0 0
Italy
State/province [73] 0 0
Catania
Country [74] 0 0
Italy
State/province [74] 0 0
Catanzaro
Country [75] 0 0
Italy
State/province [75] 0 0
Cosenza
Country [76] 0 0
Italy
State/province [76] 0 0
Firenze
Country [77] 0 0
Italy
State/province [77] 0 0
Genova
Country [78] 0 0
Italy
State/province [78] 0 0
Modena
Country [79] 0 0
Italy
State/province [79] 0 0
Monza
Country [80] 0 0
Italy
State/province [80] 0 0
Napoli
Country [81] 0 0
Italy
State/province [81] 0 0
Padova
Country [82] 0 0
Italy
State/province [82] 0 0
Palermo
Country [83] 0 0
Italy
State/province [83] 0 0
Parma
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Italy
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Pavia
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Roma
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Italy
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Bern
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Lausanne
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Luzern
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St. Gallen
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Switzerland
State/province [106] 0 0
Zürich

Funding & Sponsors
Primary sponsor type
Other
Name
Martin Schrappe
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Deutsche Krebshilfe e.V., Bonn (Germany)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The understanding of acute lymphoblastic leukemia (ALL) in childhood and adolescence has
largely changed due to extensive genetic research in recent years: ALL is now considered to
be a very heterogeneous disease group. The leukemia cells present themselves with quite
differently activated regulatory mechanisms of the malignant phenotype. The introduction of
more accurate methods of assessing therapy response ("minimal residual disease [MRD] tests")
has provided new insights into very different mechanisms of action, including factors
influenced by host factors; this has had practical clinical consequences for the use of more
individualized therapy. Multimodal therapies have enabled a cure level of over 80% for ALL in
this age group. However, the own and international study data show that the therapy toxicity
of the contemporary chemotherapy concepts has become unacceptably high, in particular with
respect to those intensified therapies used for the treatment of patients at high risk of ALL
relapse.

The AIEOP-BFM ALL 2017 study therefore aims for an innovative integrated approach that will
not only adapt the risk stratification to new prognostic markers using more comprehensive
diagnostics, but above all, qualitatively reorient the therapy. The most important
consequence will be that this study is testing immunotherapy with the bispecific antibody
blinatumomab as an alternative to particularly intensive and toxic chemotherapy elements in
precursor B-cell ALL (pB-ALL) patients with detectable chemotherapy resistance and at high
risk of relapse. With the aim to complement the effects of the conventional chemotherapy,
Blinatumomab is in addition tested in the large group of pB-ALL patients at intermediate
relapse risk with seemingly unremarkable leukemia, but who account for a large proportion of
all relapses. Targeted therapy is also used in the form of the proteasome inhibitor
bortezomib for patients with pB-ALL and slow response to the drugs of the induction
chemotherapy with the aim to overcome intrinsic chemotherapy resistance of the ALL cells. In
patients with T-lineage ALL, who have particularly poor chances for cure after relapse, the
established consolidation chemotherapy has proved to be particularly effective. This
chemotherapy phase is therefore tested in a longer and more intensive form in such T-ALL
patients with intermediate or slow early treatment response with the aim to reduce the
relapses rate in this subgroup.
Trial website
https://clinicaltrials.gov/show/NCT03643276
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Martin Schrappe, MD
Address 0 0
Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Kiel
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Anja Möricke, MD
Address 0 0
Country 0 0
Phone 0 0
+4943150020150
Fax 0 0
Email 0 0
a.moericke@pediatrics.uni-kiel.de
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03643276