Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017

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ClinicalTrials.gov Identifier: NCT03643276

Recruitment Status : Recruiting

First Posted : August 22, 2018

Last Update Posted : July 7, 2021

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Sponsor:

Collaborator:

Deutsche Krebshilfe e.V., Bonn (Germany)

Information provided by (Responsible Party):

Martin Schrappe, University Hospital Schleswig-Holstein

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Lymphoblastic Leukemia, Pediatric	Drug: Blinatumomab Drug: Bortezomib Drug: Cyclophosphamide Drug: Cytarabine Drug: Daunorubicin Drug: Myocet Drug: Dexamethasone Drug: Doxorubicin Drug: Etoposide Drug: Fludarabine Phosphate Drug: Ifosfamide Drug: 6-Mercaptopurine Drug: Methotrexate Drug: Pegaspargase Drug: Prednisolone Drug: Tioguanin Drug: Vincristine Drug: Vindesine Drug: Erwinase	Phase 3

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Detailed Description:

Patients are stratified into 4 early risk groups for therapy during the consolidation phase (T/early SR, T/early non-SR, pB/early non-HR, pB/early HR) and 5 risk groups for post-consolidation therapy (T/non-HR, T/HR, pB/SR, pB/MR, pB/HR). Risk stratification is based on immunophenotypic lineage, genetics of leukemic cells and treatment response on the basis of cytomorphology and methods for detection minimal residual disease.

The trial includes four randomized study questions testing experimental treatments on top of the risk-stratified standard chemotherapy backbone:

Primary study questions:

Randomization R-eHR: Early High-risk (early HR) pB-ALL defined by genetics and/or inadequate treatment response over the course of induction: Can the probability of event-free survival (pEFS) from time of randomization be improved by additional therapy with the proteasome inhibitor bortezomib during an extended consolidation treatment phase compared with standard extended consolidation?

Randomization R-HR: High-risk (HR) pB-ALL defined by genetics and/or inadequate treatment response by the end of consolidation: Can the pEFS from time of randomization be improved by a treatment concept including two cycles of post-consolidation immunotherapy with blinatumomab (15 µg/m²/d for 28 days per cycle) plus 4 doses intrathecal Methotrexate replacing two conventional highly intensive chemotherapy courses?

Randomization R-MR: Intermediate risk (MR) pB-ALL defined by genetics and intermediate MRD response: Can the probability of disease-free survival (pDFS) from time of randomization be improved by additional therapy with one cycle of post-reintensification immunotherapy with blinatumomab (15 µg/m²/d for 28 days)?

Randomization R-T: Early non-standard risk (early non-SR) T-ALL patients defined by treatment response over the course of induction: Can the pEFS from time of randomization be improved by the extension of the standard of care consolidation phase by 14 days with an increase of the consolidation cumulative doses of Cyclophosphamide, Cytarabine and 6-Mercaptopurine by 50%?

Secondary study questions:

All randomizations: Can the overall survival be improved by the treatment in the experimental arm?

All randomizations: What is the incidence of treatment-related toxicities and mortality in the experimental arm compared to the standard arm?

Randomization R-eHR: Can the MRD load after consolidation treatment be reduced by the additional treatment with bortezomib?

Randomization R-HR: Can treatment-related life-threatening complications and mortality during the intensified consolidation phase of high-risk treatment be reduced when replacing two intensive chemotherapy courses by two cycles of immunotherapy with blinatumomab?

Randomization R-HR: What is the proportion of patients with insufficient MRD response to blinatumomab as defined in the protocol as compared to the MRD response after the HR-2' block in the control arm?

Randomization R-HR: Can the MRD load after the first treatment cycle (HR 2'/blinatumomab) and the second cycle (HR-3'/blinatumomab) be reduced in the experimental arm when compared with conventional intensive chemotherapy? Randomization R-MR: What is the proportion of patients with positive MRD after reintensification Protocol II who become MRD-negative over the blinatumomab cycle compared to 4 weeks of standard maintenance therapy?

Randomization R-T: Can the MRD load after consolidation treatment be reduced by extension of the consolidation phase?

Standard-risk patients: Is the clinical outcome comparable to that obtained for standard-risk patients in study AIEOP-BFM ALL 2009?

A small subgroup of patients at very high relapse risk is eligible for allogeneic hematopoietic stem cell transplantation after the intensified consolidation therapy phase.

Patients with T-ALL and hyperleukocytosis (>=100,000/µL) and patients with CNS involvement at diagnosis (CNS3 status) are eligible for cranial irradiation with 12 Gy if age at time of irradiation is at least 4 years.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	5000 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Intervention Model Description:	pB-ALL/MR: 2 parallel groups (R-MR) or 2x2 factorial design (R-eHR, R-MR) depending on early risk group assignment. pB-ALL/HR: 2 parallel groups (R-HR) or 2x2 factorial design (R-eHR, R-HR) depending on early risk group assignment. T-ALL/early non-SR: 2 parallel groups (R-T). pB-ALL/SR: Single group. T-ALL/early SR: Single group.
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	International Collaborative Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017
Actual Study Start Date :	July 15, 2018
Estimated Primary Completion Date :	July 14, 2028
Estimated Study Completion Date :	July 14, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Childhood Acute Lymphoblastic Leukemia Lymphosarcoma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Cyclophosphamide Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: 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 Drug: Daunorubicin Part of standard chemotherapy Drug: Dexamethasone Part of standard chemotherapy Drug: Doxorubicin Part of standard chemotherapy Drug: 6-Mercaptopurine Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: Methotrexate Part of standard chemotherapy Drug: Pegaspargase Part of standard chemotherapy Drug: Prednisolone Part of standard chemotherapy Other Name: Prednisone Drug: Tioguanin Part of standard chemotherapy Drug: Vincristine Part of standard chemotherapy Drug: Erwinase Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
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.	Drug: Bortezomib Experimental therapy in randomization R-eHR Drug: Cyclophosphamide Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: 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 Drug: Daunorubicin Part of standard chemotherapy Drug: Dexamethasone Part of standard chemotherapy Drug: Doxorubicin Part of standard chemotherapy Drug: 6-Mercaptopurine Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: Methotrexate Part of standard chemotherapy Drug: Pegaspargase Part of standard chemotherapy Drug: Prednisolone Part of standard chemotherapy Other Name: Prednisone Drug: Tioguanin Part of standard chemotherapy Drug: Vincristine Part of standard chemotherapy Drug: Erwinase Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
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.	Drug: Blinatumomab Experimental therapy in randomizations R-HR and R-MR Drug: Cyclophosphamide Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: 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 Drug: Daunorubicin Part of standard chemotherapy Drug: Dexamethasone Part of standard chemotherapy Drug: Doxorubicin Part of standard chemotherapy Drug: 6-Mercaptopurine Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: Methotrexate Part of standard chemotherapy Drug: Pegaspargase Part of standard chemotherapy Drug: Prednisolone Part of standard chemotherapy Other Name: Prednisone Drug: Tioguanin Part of standard chemotherapy Drug: Vincristine Part of standard chemotherapy Drug: Erwinase Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
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.	Drug: Blinatumomab Experimental therapy in randomizations R-HR and R-MR Drug: Bortezomib Experimental therapy in randomization R-eHR Drug: Cyclophosphamide Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: 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 Drug: Daunorubicin Part of standard chemotherapy Drug: Dexamethasone Part of standard chemotherapy Drug: Doxorubicin Part of standard chemotherapy Drug: 6-Mercaptopurine Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: Methotrexate Part of standard chemotherapy Drug: Pegaspargase Part of standard chemotherapy Drug: Prednisolone Part of standard chemotherapy Other Name: Prednisone Drug: Tioguanin Part of standard chemotherapy Drug: Vincristine Part of standard chemotherapy Drug: Erwinase Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
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).	Drug: Cyclophosphamide Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: 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 Drug: Daunorubicin Part of standard chemotherapy Drug: Myocet Part of intensification block Myocet-FLA for patients with very high relapse risk Drug: Dexamethasone Part of standard chemotherapy Drug: Doxorubicin Part of standard chemotherapy Drug: Etoposide Part of standard chemotherapy Drug: Fludarabine Phosphate Part of intensification block Myocet-FLA for patients with very high relapse risk Drug: Ifosfamide Part of standard chemotherapy Drug: 6-Mercaptopurine Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: Methotrexate Part of standard chemotherapy Drug: Pegaspargase Part of standard chemotherapy Drug: Prednisolone Part of standard chemotherapy Other Name: Prednisone Drug: Tioguanin Part of standard chemotherapy Drug: Vincristine Part of standard chemotherapy Drug: Vindesine Part of standard chemotherapy Drug: Erwinase Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
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)	Drug: Cyclophosphamide Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: 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 Drug: Daunorubicin Part of standard chemotherapy Drug: Myocet Part of intensification block Myocet-FLA for patients with very high relapse risk Drug: Dexamethasone Part of standard chemotherapy Drug: Doxorubicin Part of standard chemotherapy Drug: Etoposide Part of standard chemotherapy Drug: Fludarabine Phosphate Part of intensification block Myocet-FLA for patients with very high relapse risk Drug: Ifosfamide Part of standard chemotherapy Drug: 6-Mercaptopurine Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: Methotrexate Part of standard chemotherapy Drug: Pegaspargase Part of standard chemotherapy Drug: Prednisolone Part of standard chemotherapy Other Name: Prednisone Drug: Tioguanin Part of standard chemotherapy Drug: Vincristine Part of standard chemotherapy Drug: Vindesine Part of standard chemotherapy Drug: Erwinase Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
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)	Drug: Blinatumomab Experimental therapy in randomizations R-HR and R-MR Drug: Cyclophosphamide Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: 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 Drug: Daunorubicin Part of standard chemotherapy Drug: Myocet Part of intensification block Myocet-FLA for patients with very high relapse risk Drug: Dexamethasone Part of standard chemotherapy Drug: Doxorubicin Part of standard chemotherapy Drug: 6-Mercaptopurine Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: Methotrexate Part of standard chemotherapy Drug: Pegaspargase Part of standard chemotherapy Drug: Prednisolone Part of standard chemotherapy Other Name: Prednisone Drug: Tioguanin Part of standard chemotherapy Drug: Vincristine Part of standard chemotherapy Drug: Erwinase Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
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)	Drug: Blinatumomab Experimental therapy in randomizations R-HR and R-MR Drug: Cyclophosphamide Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: 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 Drug: Daunorubicin Part of standard chemotherapy Drug: Myocet Part of intensification block Myocet-FLA for patients with very high relapse risk Drug: Dexamethasone Part of standard chemotherapy Drug: Doxorubicin Part of standard chemotherapy Drug: 6-Mercaptopurine Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: Methotrexate Part of standard chemotherapy Drug: Pegaspargase Part of standard chemotherapy Drug: Prednisolone Part of standard chemotherapy Other Name: Prednisone Drug: Tioguanin Part of standard chemotherapy Drug: Vincristine Part of standard chemotherapy Drug: Erwinase Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
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.	Drug: Cyclophosphamide Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: 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 Drug: Daunorubicin Part of standard chemotherapy Drug: Dexamethasone Part of standard chemotherapy Drug: Doxorubicin Part of standard chemotherapy Drug: 6-Mercaptopurine Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: Methotrexate Part of standard chemotherapy Drug: Pegaspargase Part of standard chemotherapy Drug: Prednisolone Part of standard chemotherapy Other Name: Prednisone Drug: Tioguanin Part of standard chemotherapy Drug: Vincristine Part of standard chemotherapy Drug: Erwinase Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
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)	Drug: Cyclophosphamide Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: 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 Drug: Daunorubicin Part of standard chemotherapy Drug: Myocet Part of intensification block Myocet-FLA for patients with very high relapse risk Drug: Dexamethasone Part of standard chemotherapy Drug: Doxorubicin Part of standard chemotherapy Drug: Etoposide Part of standard chemotherapy Drug: Fludarabine Phosphate Part of intensification block Myocet-FLA for patients with very high relapse risk Drug: Ifosfamide Part of standard chemotherapy Drug: 6-Mercaptopurine Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: Methotrexate Part of standard chemotherapy Drug: Pegaspargase Part of standard chemotherapy Drug: Prednisolone Part of standard chemotherapy Other Name: Prednisone Drug: Tioguanin Part of standard chemotherapy Drug: Vincristine Part of standard chemotherapy Drug: Vindesine Part of standard chemotherapy Drug: Erwinase Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
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)	Drug: Cyclophosphamide Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: 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 Drug: Daunorubicin Part of standard chemotherapy Drug: Myocet Part of intensification block Myocet-FLA for patients with very high relapse risk Drug: Dexamethasone Part of standard chemotherapy Drug: Doxorubicin Part of standard chemotherapy Drug: Etoposide Part of standard chemotherapy Drug: Fludarabine Phosphate Part of intensification block Myocet-FLA for patients with very high relapse risk Drug: Ifosfamide Part of standard chemotherapy Drug: 6-Mercaptopurine Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: Methotrexate Part of standard chemotherapy Drug: Pegaspargase Part of standard chemotherapy Drug: Prednisolone Part of standard chemotherapy Other Name: Prednisone Drug: Tioguanin Part of standard chemotherapy Drug: Vincristine Part of standard chemotherapy Drug: Vindesine Part of standard chemotherapy Drug: Erwinase Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
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.	Drug: Cyclophosphamide Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: 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 Drug: Daunorubicin Part of standard chemotherapy Drug: Dexamethasone Part of standard chemotherapy Drug: Doxorubicin Part of standard chemotherapy Drug: 6-Mercaptopurine Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T Drug: Methotrexate Part of standard chemotherapy Drug: Pegaspargase Part of standard chemotherapy Drug: Prednisolone Part of standard chemotherapy Other Name: Prednisone Drug: Tioguanin Part of standard chemotherapy Drug: Vincristine Part of standard chemotherapy Drug: Erwinase Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction

Outcome Measures

Primary Outcome Measures :

Event-free survival [ Time Frame: Assessed up to 120 months from start of study ]
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.
Disease-free survival [ Time Frame: Assessed up to 120 months from start of study ]
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.

Secondary Outcome Measures :

Survival [ Time Frame: Assessed up to 120 months from start of study ]
All patients/randomizations: Time until death from any cause, starting at the same time point as the EFS/DFS.
Treatment-related mortality [ Time Frame: Assessed up to 120 months from start of study ]
Frequency and incidence of treatment-related mortality in induction or continuous complete remission
Adverse Events of interest/Serious Adverse Events [ Time Frame: Assessed up to 120 months from start of study ]
Frequency and incidence of adverse events of interest and serious adverse events in specific protocol phases, randomized arms and overall during follow-up
MRD response [ Time Frame: 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). ]
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)
Proportion of patients with Blina Poor-Response [ Time Frame: Measurements of MRD response intended after 30 weeks from individual start of treatment, assessment of proportion at 120 months from start of study ]
Proportion of patients with poor MRD response to the first Blinatumomab cycle ("Blinatumomab Poor-Response") (R-HR)

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:	up to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03643276

Contacts

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Contact: Anja Möricke, MD	+4943150020150	a.moericke@pediatrics.uni-kiel.de
Contact: Lile Bauer	+4943150020152	lile.bauer@uksh.de

Locations

Show 115 study locations

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Australia
Sydney Children's Hospital	Recruiting
Sydney, Australia
Contact: Draga Barbaric
The Children's Hospital at Westmead	Recruiting
Westmead, Australia
Contact: Luciano Dalla-Pozza
Austria
Univ.Klinik für Kinder- und Jugendheilkunde Graz	Recruiting
Graz, Austria
Contact: Martin Benesch
Univ.Klinik für Kinder- und Jugendheilkunde Innsbruck	Recruiting
Innsbruck, Austria
Contact: Bernhard Meister
Kepler Universitätsklinikum	Recruiting
Linz, Austria
Contact: Georg Ebetsberger
LKH Salzburg	Recruiting
Salzburg, Austria
Contact: Neil Jones
St. Anna Kinderspital	Recruiting
Vienna, Austria
Contact: Andishe Attarbaschi
Czechia
University Hospital Brno	Recruiting
Brno, Czechia
Contact: Jaroslav Štěrba
University Hospital Hradec Králové	Recruiting
Hradec Králové, Czechia
Contact: Jiří Hak
University Hospital Olomouc	Recruiting
Olomouc, Czechia
Contact: Dagmar Pospíšilová
University Hospital Ostrava-Poruba	Recruiting
Ostrava-Poruba, Czechia
Contact: Tomáš Kuhn
University Hospital Plzeň	Recruiting
Plzeň, Czechia
Contact: Tomáš Votava
University Hospital Motol	Recruiting
Praha, Czechia
Contact: Jan Starý
Masaryk´s Hospital Ústí nad Labem	Recruiting
Ústí nad Labem, Czechia
Contact: Daniela Procházková
Regional Hospital České Budějovice	Recruiting
České Budějovice, Czechia
Contact: Pavel Timr
Germany
Kinderklinik der med. Fakultät der RWTH, Bereich Hämatologie/Onkologie	Recruiting
Aachen, Germany, 52074
Contact: Udo Kontny +49 241808 ext 9902 ukontny@ukaachen.de
I. Klinik für Kinder u. Jugendliche, Klinikum Augsburg, Hämatologie/ Onkologie	Recruiting
Augsburg, Germany, 86156
Contact: Michael Frühwald +49 821400 ext 3631
Klinikum Berlin-Buch II. Kinderklinik, Bereich Onkologie/Allg. Pädiatrie	Recruiting
Berlin, Germany, 13125
Contact: Lothar Schweigerer +49 309401 ext 2367 lschweigerer@berlin.helio-kliniken.de
Kinderklinik der Charité, Campus Virchow Klinikum (CVK), Abt.: Kinderhämatologie	Recruiting
Berlin, Germany, 13353
Contact: Arend Stackelberg +49 30450566 ext 833 arend.stackelberg@charite.de
Städtisches Krankenhaus, Kinderklinik	Recruiting
Braunschweig, Germany, 38118
Contact: Wolfgang Eberl +49 531595 ext 1424 w.eberl@klinkum-braunschweig.de
Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie / Onkologie	Recruiting
Chemnitz, Germany, 09009
Contact: Andre Hofmann +49 3713332 ext 4287 a.hofmann@skc.de
Carl-Thiem-Klinikum, Kinderklinik, Abt. Hämatologie/Onkologie	Recruiting
Cottbus, Germany, 03048
Contact: Georg Schwabe +49 35546 ext 2332
Vestische Kinder- u. Jugendklinik, Universitätsklinik Witten/Herdecke	Recruiting
Datteln, Germany, 45711
Contact: Thomas Wiesel +49 236397 ext 5846 th.wiesel@kinderklinik-datteln.de
Klinikum Dortmund, Klinik f. Kinder- und Jugendmedizin	Recruiting
Dortmund, Germany, 44137
Contact: Dominik Schneider +49 2319532 ext 1050 dominik.schneider@klinikumdo.de
Universitatsklinikum Carl Gustav Carus	Recruiting
Dresden, Germany, D-01307
Contact: R. Knöfler, MD
Universitätsklinik	Recruiting
Düsseldorf, Germany
Contact: Arndt Borkhardt, Prof.
Helios Klinikum Erfurt GmbH, Klinik für Kinderheilkunde	Recruiting
Erfurt, Germany, 99089
Contact: Axel Sauerbrey +49 36178 ext 4501 axel.sauerbrey@helios-kliniken.de
Universitaets - Kinderklinik	Recruiting
Erlangen, Germany, 91054
Contact: M. Metzler, MD
Universitaetsklinikum Essen	Recruiting
Essen, Germany, D-45147
Contact: Rita Beier, MD
Klinikum der J.W. Goethe Universitaet	Recruiting
Frankfurt, Germany, D-60590
Contact: Thomas Klingebiel, MD 49-69-6301-5094 thomas.klingebiel@kgu.de
Universitaetskinderklinik - Universitaetsklinikum Freiburg	Recruiting
Freiburg, Germany, D-79106
Contact: Charlotte Niemeyer, MD 49-761-270-4506 charlotte.niemeyer@uniklinik-freiburg.de
Klinikum der Justus-Liebig-Universität, Zentrum für Kinderheilkunde, Abt. Hämatologie/Onkologie	Recruiting
Gießen, Germany, 35385
Contact: Christine Mauz-Körholz
Klinik und Poliklinik für Kinder und Jugendmedizin, Allgemeine Pädiatrie mit Poliklinik/Pädiatrische Onkologie und Hämatologie	Recruiting
Greifswald, Germany, 17475
Contact: Holger Lode +49 383486 ext 6325 holger.lode@uni-greifswald.de
Universitäts-Kinderklinik Päd. I, Hämatologie/Onkologie	Recruiting
Göttingen, Germany, 37099
Contact: Ingrid Kühnle +49 55139 ext 6201
Medizinische Hochschule Hannover, Zentrum Kinderheilkunde u. Jugendmedizin	Recruiting
Hannover, Germany, 30625
Contact: Christin Linderkamp +49 511532 ext 6710 linderkamp.christin@mh-hannover.de
Universitäts-Kinderklinik, Päd. Onkologie, Hämatologie, und Immunologie	Recruiting
Heidelberg, Germany, 69120
Contact: Wolfgang Behnisch +49 622156 ext 4555 wolfgang.behnisch@med.uni-heidelberg.de
Klinikum Heilbronn GmbH, Klinik für Kinderheilkunde und Jugendmedizin/Perinatalzentrum	Recruiting
Heilbronn, Germany, 74078
Contact: Hermann Full +49 713149 ext 3702 hermann.full@slk-kliniken.de
Gemeinschaftskrankenhaus Herdecke, Kinderabteilung	Recruiting
Herdecke, Germany, 58313
Contact: Alfred Längler +49 233062 ext 3893 a.laengler@gemeinschaftskrankenhaus.de
Universitaetsklinikum des Saarlandes	Recruiting
Homburg, Germany, 66421
Contact: Norbert Graf 49-6841-168-8397
Klinikum, der Friedrich-Schiller-Universität, Klinik für Kinder- und Jugendmedizin	Recruiting
Jena, Germany, 7740
Contact: Bernd Gruhn +49 364193 ext 8220 bernd.gruhn@med.uni-jena.de
Staedtisches Klinikum Karlsruhe gGmbH	Recruiting
Karlsruhe, Germany, 76133
Contact: A. Leipold 49-721-9740
Klinikum Kassel	Recruiting
Kassel, Germany, D-34125
Contact: Michaela Nathrath, MD 49-561-980-3382
Klinik für Allgemeine Paediatrie, Univ.-Klinikum Schleswig-Holstein, Campus Kiel	Recruiting
Kiel, Germany, 24105
Contact: Martin Schrappe +49 431597 ext 1620 m.schrappe@pediatrics.uni-kiel.de
Kliniken der Stadt Köln GmbH, Kinderkrankenhaus Riehl	Recruiting
Köln, Germany, 50735
Contact: Aram Prokop +49 2218907 ext 5158 prokopa@klinken-koeln.de
Med. Einrichtungen der Universität zu Köln, Klinik für Allg. Kinderheilkunde, Onkologisch-hämatologische Station	Recruiting
Köln, Germany, 50937
Contact: Thorsten Simon +49 221478 ext 4380 thorsten.simon@uk-koeln.de
Department für Frauen- und Kindermedizin, Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie	Recruiting
Leipzig, Germany, 04103
Contact: Lars Fischer 0341-97 26
Universität zu Lübeck, Klinik für Kinder- u. Jugendmedizin, Abt. Hämatologie/ Onkologie/Immunologie	Recruiting
Lübeck, Germany, 23538
Contact: Melchior Lauten +49 451500 ext 2557 lauten@paedia.ukl.mu-luebeck.de
Universitätsklinikum Magdeburg, Klinik für Päd. Hämatologie/Onkologie	Recruiting
Magdeburg, Germany, 39120
Contact: Peter Vorwerk +49 391671 ext 7210 peter.vorwerk@med.ovgu.de
Klinikum Mannheim gGmbH, Kinderklinik, Abt. Hämatologie/Onkologie	Recruiting
Mannheim, Germany, 68167
Contact: Matthias Dürken +49 621383 ext 2244 matthias.duerken@kikli.ma.uni-heidelberg.de
Universitätsklinikum	Recruiting
Mannheim, Germany
Contact: Matthias Dürken, Dr.
Johannes Wesling Klinikum Minden	Recruiting
Minden, Germany, 32429
Contact: Bernhard Erdlenbruch +49 571 ext 8010 bernhard.erdlenbruch@klinikum-minden.de
Städt. Krankenhaus München GmbH, Krankenhaus München-Schwabingen, Kinderklinik d. TU	Recruiting
München, Germany, 80804
Contact: Angela Wawer +49 893068 ext 2261 angela.wawer@lrz.tum.de
Ludwig-Maximilian-Universität, Dr. von Haunersches Kinderspital	Recruiting
München, Germany
Contact: Tobias Feuchtinger
Universitäts-Kinderklinik, Päd. Hämatologie und Onkologie	Recruiting
Münster, Germany, 48149
Contact: Claudia Rössig +49 251834 ext 5644 rossig@ukmuenster.de
Cnopf'sche Kinderklinik, Onkologie	Recruiting
Nürnberg, Germany, 90419
Contact: Wolfram Scheurlen +49 91133 ext 40323 wolfram.scheurlen@diakonieneudettelsau.de
Klinikum Oldenburg gGmbH, Zentrum für Kinder- u. Jugendmedizin, (Elisabeth Kinderkrankenhaus)	Recruiting
Oldenburg, Germany, 26133
Contact: Hermann Müller +49 441403 ext 2013 mueller.hermann@klinikum-oldenburg.de
Universitätsklinikum	Recruiting
Regensburg, Germany
Contact: Selim Corbacioglu, Dr.
Universitäts-Kinderklinik	Recruiting
Rostock, Germany, 18055
Contact: Carl-Friedrich Classen +49 381494 ext 7000 carl-friedrich.classen@med.uni-rostock.de
Asklepios-Klinik, Sankt Augustin GmbH	Recruiting
Sankt Augustin, Germany, 53757
Contact: Harald Reinhard +49 224124 ext 9304 h.reinhard@asklepios.com
HELIOS Kliniken Schwerin, Klinik f. Kinder-u. Jugendmedizin	Recruiting
Schwerin, Germany, 19049
Contact: Christian Güttel +49 385520 ext 2710 christian.guettel@helios-kliniken.de
Olga-Hospital, Kinderklinik, Pädiatrisches Zentrum, Abt. Hämatologie/Onkologie	Recruiting
Stuttgart, Germany, 70176
Contact: Stefan Bielack +49 711992 ext 2461 st.bielack@olgahospital.de
Krankenanstalt Trier, Mutterhaus der Borromaeerinnen, Pädiatrische Abteilung	Recruiting
Trier, Germany, 54290
Contact: Stefan Weis +49 651947 ext 2654 weis@mutterhaus.de
Universitaetsklinikum Tuebingen	Recruiting
Tuebingen, Germany, D-72076
Contact: Martin Ebinger, MD
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm	Recruiting
Ulm, Germany, D-89075
Contact: Klaus M. Debatin, MD 49-731-5000 klaus-michael.debatin@medizin.uni-ulm.de
Stadtkrankenhaus, Kinderklinik	Recruiting
Wolfsburg, Germany, 38440
Contact: Sally Mukodzi +49 5361 ext 8000 sally.mukidzi@klinikum-wolfsburg.de
Universitaets - Kinderklinik Wuerzburg	Recruiting
Wuerzburg, Germany, D-97080
Contact: P. G. Schlegel, MD 49-931-2012-7856 schlegel@mail.uni-wuerzburg.de
Israel
Soroka University Medical Center	Recruiting
Beer Sheva, Israel
Contact: Joseph Kapelushnik
Rambam Health Care Campus	Recruiting
Haifa, Israel
Contact: Nira Arad-Cohen
Hadassah Medical center	Recruiting
Jerusalem, Israel
Contact: Gal Goldstein
Schneider Children Medical Center of Israel	Recruiting
Petach-Tikva, Israel
Contact: Gil Gilad
Sheba Medical Center Tel-Hashomer	Recruiting
Ramat Gan, Israel
Contact: Bella Bielorai
Dana children hospital	Recruiting
Tel-Aviv, Israel
Contact: Ronit Elhasid
Italy
Azienda ospedali riuniti	Recruiting
Ancona, Italy
Contact: Paolo Pierani
AOUC Policlinico Bari	Recruiting
Bari, Italy
Contact: Nicola Santoro
A.O. Papa Giovanni XXIII	Recruiting
Bergamo, Italy
Contact: Massimo Provenzi
Università di Bologna	Recruiting
Bologna, Italy
Contact: Andrea Pession
ASST Spedali Civili di Brescia	Recruiting
Brescia, Italy
Contact: Fulvio Porta
Ospedale Businco	Recruiting
Cagliari, Italy
Contact: Rosa Maria Mura
Azienda ospedaliero universitaria	Recruiting
Catania, Italy
Contact: Luca Lo Nigro
AO Pugliese Ciaccio	Recruiting
Catanzaro, Italy
Contact: Caterina Consarino
S.O. Annunziata - A. O. Cosenza	Recruiting
Cosenza, Italy
Contact: Domenico Sperlì
Ospedale Meyer	Recruiting
Firenze, Italy
Contact: Tommaso Casini
Istituto Giannina Gaslini	Recruiting
Genova, Italy
Contact: Concetta Micalizzi
Policlinico di Modena Azienda Ospedaliero-Universitaria	Recruiting
Modena, Italy
Contact: Monica Cellini
Clinica pediatrica Fondazione MBBM	Recruiting
Monza, Italy
Contact: Andrea Biondi
A.O.U. Vanvitelli	Recruiting
Napoli, Italy
Contact: Francesca Rossi
AORN Santobono Pausilipon	Recruiting
Napoli, Italy
Contact: Rosanna Parasole
Azienda ospedaliera di Padova	Recruiting
Padova, Italy
Contact: Maria Caterina Putti
Ospedale Civico ARNAS Civico e Di Cristina	Recruiting
Palermo, Italy
Contact: Ottavio Ziino
Azienda ospedaliero-universitaria di Parma	Recruiting
Parma, Italy
Contact: Angelica Barone
Fondazione IRCCS Policlinico San Matteo	Recruiting
Pavia, Italy
Contact: Marco Zecca
Ospedale S. Maria della misericordia	Recruiting
Perugia, Italy
Contact: Maurizio Caniglia
Ospedale Civile di Pescara	Recruiting
Pescara, Italy
Contact: Daniela Onofrillo
Ospedale Santa Chiara Pisa	Recruiting
Pisa, Italy
Contact: Emanuela De Marco
Grande ospedale metropolitano B-M-M	Recruiting
Reggio Calabria, Italy
Contact: Francesca Ronco
Ospedale infermi	Recruiting
Rimini, Italy
Contact: Roberta Pericoli
Fondazione Policlinico Gemelli	Recruiting
Roma, Italy
Contact: Antonio Ruggiero
Ospedale Bambino Gesù	Recruiting
Roma, Italy
Contact: Franco Locatelli
Policlinico Umberto I Università Sapienza di Roma	Recruiting
Roma, Italy
Contact: Robin Foà
Ospedale "Casa sollievo della sofferenza"	Recruiting
San Giovanni Rotondo, Italy
Contact: Saverio Ladogana
A.O.U. Città della salute e della scienza di Torino	Recruiting
Torino, Italy
Contact: Franca Fagioli
IRCCS Burlo Garofolo	Recruiting
Trieste, Italy
Contact: Valentina Kiren
AOU Verona	Recruiting
Verona, Italy
Contact: Simone Cesaro
Slovakia
Klinika pediatrickej hematológie a onkológie SZU a DFNsP	Recruiting
Banská Bystrica, Slovakia
Contact: Eva Bubanská
Comenius University Children's Hospital	Recruiting
Bratislava, Slovakia
Contact: Alexandra Kolenova
Detská fakultná nemocnica Košice	Recruiting
Košice, Slovakia
Contact: Natália Galóová
Switzerland
Kantonsspital Aarau	Recruiting
Aarau, Switzerland
Contact: Katrin Scheinemann
Universitäts-Kinderspital beider Basel	Recruiting
Basel, Switzerland
Contact: Nicolas von der Weid
Ospedale San Giovanni Bellinzona	Recruiting
Bellinzona, Switzerland
Contact: Pierluigi Brazzola
Inselspital Bern	Recruiting
Bern, Switzerland
Contact: Jochen Rössler
HUG Hôpitaux Universitaires de Gèneve	Recruiting
Genève, Switzerland
Contact: Frederic Baleydier
CHUV Centre Hospitalier Universitaire Vaudois	Recruiting
Lausanne, Switzerland
Contact: Francesco Ceppi
Luzerner Kantonsspital-Kinderspital Luzern	Recruiting
Luzern, Switzerland
Contact: Freimut Schilling
Ostschweizer Kinderspital	Recruiting
St. Gallen, Switzerland
Contact: Jeanette Greiner
Universitäts-Kinderspital Zürich	Recruiting
Zürich, Switzerland
Contact: Felix Niggli

Sponsors and Collaborators

Martin Schrappe

Deutsche Krebshilfe e.V., Bonn (Germany)

Investigators

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Principal Investigator:	Martin Schrappe, MD	Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Kiel

More Information

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Responsible Party:	Martin Schrappe, Professor MD, FRCP (Glasg), Chair of Pediatrics I, University Hospital Schleswig-Holstein
ClinicalTrials.gov Identifier:	NCT03643276
Other Study ID Numbers:	AIEOP-BFM ALL 2017
First Posted:	August 22, 2018 Key Record Dates
Last Update Posted:	July 7, 2021
Last Verified:	July 2021

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Martin Schrappe, University Hospital Schleswig-Holstein:


Acute Lymphoblastic Leukemia Childhood Pediatric Immunotherapy Blinatumomab	Proteasome Inhibitor Bispecific antibody Bortezomib Chemotherapy Randomized trial

Additional relevant MeSH terms:

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Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Dexamethasone Prednisone Prednisolone Cyclophosphamide Ifosfamide	Doxorubicin Methotrexate Fludarabine Fludarabine phosphate Etoposide Vincristine Bortezomib Daunorubicin Mercaptopurine Pegaspargase Blinatumomab Vindesine Asparaginase Immunosuppressive Agents Immunologic Factors

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