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Trial details imported from ClinicalTrials.gov

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


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Registration number
NCT03643276
Ethics application status
Date submitted
12/07/2018
Date registered
22/08/2018
Date last updated
29/11/2023

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 - Myocet
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 Myocet-FLA (Myocet, 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 Myocet-FLA (Myocet, 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 Myocet-FLA (Myocet, 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 Myocet-FLA (Myocet, 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 Myocet-FLA (Myocet, 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 Myocet-FLA (Myocet, 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 Myocet-FLA for patients with very high relapse risk

Treatment: Drugs: Daunorubicin
Part of standard chemotherapy

Treatment: Drugs: Myocet
Part of intensification block Myocet-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 Myocet-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
Timepoint [1] 0 0
Assessed up to 120 months from start of study
Primary outcome [2] 0 0
Disease-free survival
Timepoint [2] 0 0
Assessed up to 120 months from start of study
Secondary outcome [1] 0 0
Survival
Timepoint [1] 0 0
Assessed up to 120 months from start of study
Secondary outcome [2] 0 0
Treatment-related mortality
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
Timepoint [3] 0 0
Assessed up to 120 months from start of study
Secondary outcome [4] 0 0
MRD response
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
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
Sex
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
15/07/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
14/07/2028
Actual
Sample size
Target
5000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 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
Country [84] 0 0
Italy
State/province [84] 0 0
Pavia
Country [85] 0 0
Italy
State/province [85] 0 0
Perugia
Country [86] 0 0
Italy
State/province [86] 0 0
Pescara
Country [87] 0 0
Italy
State/province [87] 0 0
Pisa
Country [88] 0 0
Italy
State/province [88] 0 0
Reggio Calabria
Country [89] 0 0
Italy
State/province [89] 0 0
Rimini
Country [90] 0 0
Italy
State/province [90] 0 0
Roma
Country [91] 0 0
Italy
State/province [91] 0 0
San Giovanni Rotondo
Country [92] 0 0
Italy
State/province [92] 0 0
Torino
Country [93] 0 0
Italy
State/province [93] 0 0
Trieste
Country [94] 0 0
Italy
State/province [94] 0 0
Verona
Country [95] 0 0
Slovakia
State/province [95] 0 0
Banská Bystrica
Country [96] 0 0
Slovakia
State/province [96] 0 0
Bratislava
Country [97] 0 0
Slovakia
State/province [97] 0 0
Košice
Country [98] 0 0
Switzerland
State/province [98] 0 0
Aarau
Country [99] 0 0
Switzerland
State/province [99] 0 0
Basel
Country [100] 0 0
Switzerland
State/province [100] 0 0
Bellinzona
Country [101] 0 0
Switzerland
State/province [101] 0 0
Bern
Country [102] 0 0
Switzerland
State/province [102] 0 0
Genève
Country [103] 0 0
Switzerland
State/province [103] 0 0
Lausanne
Country [104] 0 0
Switzerland
State/province [104] 0 0
Luzern
Country [105] 0 0
Switzerland
State/province [105] 0 0
St. Gallen
Country [106] 0 0
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/study/NCT03643276
Trial related presentations / publications
Tufekci O, Evim MS, Gunes AM, Celkan T, Karapinar DY, Kaya Z, Baysal B, Baytan B, Kocak U, Yilmaz S, Cinar S, Oren H. Assessment of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia: A Multicenter Study From Turkey. J Pediatr Hematol Oncol. 2022 Mar 1;44(2):e396-e402. doi: 10.1097/MPH.0000000000002419.
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
[email protected]
Contact person for scientific queries



Summary Results

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

Additional trial details provided through ANZCTR
Accrual to date
50
Recruiting in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 59
Sydney Children's Hospital
Recruitment hospital [2] 60
The Children's Hospital at Westmead
Recruitment postcode(s) [1] 63
2031
Recruitment postcode(s) [2] 64
2145
Funding & Sponsors
Primary sponsor
Other Collaborative groups
Primary sponsor name
Australian and New Zealand Children's Haematology and Oncology Group
Primary sponsor address
27-31 Wright Street, Clayton, VIC, 3168
Primary sponsor country
Australia
Ethics approval
Ethics application status
Approved
 
Public notes

Contacts
Principal investigator
Title 205 0
Dr
Name 205 0
Draga Barbaric
Address 205 0
High Street, Randwick NSW 2031
Country 205 0
Australia
Phone 205 0
Fax 205 0
Email 205 0
[email protected]
Contact person for public queries
Title 206 0
Mrs
Name 206 0
Robyn Strong
Address 206 0
27-31 Wright Street, Clayton, VIC, 3168
Country 206 0
Australia
Phone 206 0
+613 8572 2684
Fax 206 0
+613 9902 4810
Email 206 0
[email protected]
Contact person for scientific queries
Title 207 0
Dr
Name 207 0
Draga Barbaric
Address 207 0
High Street, Randwick NSW 2031
Country 207 0
Australia
Phone 207 0
Fax 207 0
Email 207 0
[email protected]