RecruitingNCT03643276Updated Apr 6, 2025

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

A Phase 3 interventional study of Blinatumomab and Bortezomib in Acute Lymphoblastic Leukemia, Pediatric, sponsored by Martin Schrappe. Recruiting at 115 sites in 8 countries. Open to participants aged Up to 17 Years. Per ClinicalTrials.gov, last updated 2025-04-06.

Sponsored by Martin Schrappe · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 5,000
Allocation: Randomized
Ages: Up to 17 Years
Sex: All

Study 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.

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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.

Conditions studied

Acute Lymphoblastic Leukemia, Pediatric

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Keywords

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

Who can participate

Ages eligible: Up to 17 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial assignment
Masking: None (open label)
Enrollment: 5,000 participants (estimated)

Study arms

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 · Drug: Cytarabine · Drug: Daunorubicin · Drug: Dexamethasone · Drug: Doxorubicin · Drug: 6-Mercaptopurine · Drug: Methotrexate · Drug: Pegaspargase · Drug: Prednisolone · Drug: Tioguanin · Drug: Vincristine · Drug: Erwinase
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 · Drug: Cyclophosphamide · Drug: Cytarabine · Drug: Daunorubicin · Drug: Dexamethasone · Drug: Doxorubicin · Drug: 6-Mercaptopurine · Drug: Methotrexate · Drug: Pegaspargase · Drug: Prednisolone · Drug: Tioguanin · Drug: Vincristine · Drug: Erwinase
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 · Drug: Cyclophosphamide · Drug: Cytarabine · Drug: Daunorubicin · Drug: Dexamethasone · Drug: Doxorubicin · Drug: 6-Mercaptopurine · Drug: Methotrexate · Drug: Pegaspargase · Drug: Prednisolone · Drug: Tioguanin · Drug: Vincristine · Drug: Erwinase
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 · Drug: Bortezomib · Drug: Cyclophosphamide · Drug: Cytarabine · Drug: Daunorubicin · Drug: Dexamethasone · Drug: Doxorubicin · Drug: 6-Mercaptopurine · Drug: Methotrexate · Drug: Pegaspargase · Drug: Prednisolone · Drug: Tioguanin · Drug: Vincristine · Drug: Erwinase
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 · 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
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 · 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
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 · Drug: Cyclophosphamide · Drug: Cytarabine · Drug: Daunorubicin · Drug: Myocet · Drug: Dexamethasone · Drug: Doxorubicin · Drug: 6-Mercaptopurine · Drug: Methotrexate · Drug: Pegaspargase · Drug: Prednisolone · Drug: Tioguanin · Drug: Vincristine · Drug: Erwinase
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 · Drug: Cyclophosphamide · Drug: Cytarabine · Drug: Daunorubicin · Drug: Myocet · Drug: Dexamethasone · Drug: Doxorubicin · Drug: 6-Mercaptopurine · Drug: Methotrexate · Drug: Pegaspargase · Drug: Prednisolone · Drug: Tioguanin · Drug: Vincristine · Drug: Erwinase
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.
Drug: Cyclophosphamide · Drug: Cytarabine · Drug: Daunorubicin · Drug: Dexamethasone · Drug: Doxorubicin · Drug: 6-Mercaptopurine · Drug: Methotrexate · Drug: Pegaspargase · Drug: Prednisolone · Drug: Tioguanin · Drug: Vincristine · Drug: Erwinase
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 · 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
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 · 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
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.
Drug: Cyclophosphamide · Drug: Cytarabine · Drug: Daunorubicin · Drug: Dexamethasone · Drug: Doxorubicin · Drug: 6-Mercaptopurine · Drug: Methotrexate · Drug: Pegaspargase · Drug: Prednisolone · Drug: Tioguanin · Drug: Vincristine · Drug: Erwinase

Interventions

DrugBlinatumomab
Experimental therapy in randomizations R-HR and R-MR
DrugBortezomib
Experimental therapy in randomization R-eHR
DrugCyclophosphamide
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
DrugCytarabine
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
DrugDaunorubicin
Part of standard chemotherapy
DrugMyocet
Part of intensification block Myocet-FLA for patients with very high relapse risk
DrugDexamethasone
Part of standard chemotherapy
DrugDoxorubicin
Part of standard chemotherapy
DrugEtoposide
Part of standard chemotherapy
DrugFludarabine Phosphate
Part of intensification block Myocet-FLA for patients with very high relapse risk
DrugIfosfamide
Part of standard chemotherapy
Drug6-Mercaptopurine
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
DrugMethotrexate
Part of standard chemotherapy
DrugPegaspargase
Part of standard chemotherapy
DrugPrednisolone
Part of standard chemotherapy
Also known as: Prednisone
DrugTioguanin
Part of standard chemotherapy
DrugVincristine
Part of standard chemotherapy
DrugVindesine
Part of standard chemotherapy
DrugErwinase
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction

What researchers measure

Primary outcomes

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.
Time frame: Assessed up to 120 months from start of study
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.
Time frame: Assessed up to 120 months from start of study

Secondary outcomes

Survival
All patients/randomizations: Time until death from any cause, starting at the same time point as the EFS/DFS.
Time frame: Assessed up to 120 months from start of study
Treatment-related mortality
Frequency and incidence of treatment-related mortality in induction or continuous complete remission
Time frame: Assessed up to 120 months from start of study
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
Time frame: Assessed up to 120 months from start of study
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)
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).
Proportion of patients with Blina Poor-Response
Proportion of patients with poor MRD response to the first Blinatumomab cycle ("Blinatumomab Poor-Response") (R-HR)
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

Study locations

115 of 115 sites recruiting

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

Showing the first 100 of 115 sites across 8 countries.

References and documents

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. PubMed 35129146 ↗

Registry details

Key details

Study ID: NCT03643276
Lead sponsor: Martin Schrappe
Collaborators: Deutsche Krebshilfe e.V., Bonn (Germany)
Responsible party: Martin Schrappe (Professor MD, FRCP (Glasg), Chair of Pediatrics I, University Hospital Schleswig-Holstein) — Sponsor-investigator
First posted: Aug 22, 2018
Start date: Jul 15, 2018
Primary completion: Jul 14, 2028 (estimated)
Completion: Jul 14, 2028 (estimated)
Last update: Apr 6, 2025

Study contacts

Anja Möricke, MD

Contact

a.moericke@pediatrics.uni-kiel.de

+4943150020150

Lile Bauer

Contact

lile.bauer@uksh.de

+4943150020152

Martin Schrappe, MD

principal investigator · Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Kiel

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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