International collaborative treatment protocol for children and adolescents with acute lymphoblastic leukemia

• Register: EUCTR
• Last refreshed on: 23 May 2022
• Main ID: EUCTR2016-001935-12-AT
• Date of registration: 05/07/2018
• Prospective Registration: Yes
• Primary sponsor: Universitätsklinikum Schleswig-Holstein, Campus Kiel
• Public title: International collaborative treatment protocol for children and adolescents with acute lymphoblastic leukemia
• Scientific title: AIEOP-BFM ALL 2017 - International collaborative treatment protocol for children and adolescents with acute lymphoblastic leukemia - AIEOP-BFM ALL 2017
• Date of first enrolment: 31/08/2018
• Target sample size: 5420
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001935-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 14
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Czech Republic, Czechia, Germany, Israel, Italy, Slovakia, Switzerland

Contacts

• Name: Study Coordinator
• Affiliation: Universitätsklinikum Schleswig-Holstein, Campus Kiel

• Name: Study Coordinator
• Affiliation: Universitätsklinikum Schleswig-Holstein, Campus Kiel

Key inclusion & exclusion 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

Are the trial subjects under 18? yes
Number of subjects for this age range: 5000
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 Prednisolone equivalent for more than two weeks during the last month before diagnosis
- treatment started according to another protocol
- underlying diseases that does not allow treatment according to the protocol
- 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 that interferes with the protocol
- other condition (either pre-existing or related to leukemia biology as present at diagnosis) or circumstances that significantly conflict with the treatment according to the protocol



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

acute lymphoblastic leukemia in children and adolescents <18 years of age

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Pharmaceutical Form: Tablet
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2
Current Sponsor code: DEXA

Pharmaceutical Form: Solution for injection
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2
Current Sponsor code: DEXA

Pharmaceutical Form: Tablet
INN or Proposed INN: PREDNISOLONE
CAS Number: 50-24-8
Current Sponsor code: PRED

Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: PREDNISOLONE
CAS Number: 50-24-8
Current Sponsor code: PRED

Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: VINCRISTINE
CAS Number: 57-22-7
Current Sponsor code: VCR

Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: DAUNORUBICIN
CAS Number: 20830-81-3
Current Sponsor code: DNR

Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DOXORUBICIN HYDROCHLORIDE
CAS Number: 25316-40-9
Current Sponsor code: DOX

Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: CYCLOPHOSPHAMIDE
CAS Number: 50-18-0
Current Sponsor code: CPM

Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: CYTARABINE
CAS Number: 147-94-4
Current Sponsor code: ARA-C

Pharmaceutical Form: Tablet
INN or Proposed INN: MERCAPTOPURINE
CAS Number: 50-44-2
Current Sponsor code: 6-MP

Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: METHOTREXATE
CAS Number: 59-05-2
Current Sponsor code: HD-MTX

Pharmaceutical Form: Tablet
INN or Proposed INN: METHOTREXATE
CAS Number: 59-05-2
Current Sponsor code: MTX

Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: METHOTREXATE
CAS Number: 59-05-2
Current Sponsor code: MTX i.th.

Pharmaceutical Form: Powder for solution for injection
I

Primary Outcome(s)

Main Objective: - 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 pEFS from time of randomization be improved by additional therapy with the proteasome inhibitor Bortezomib during an extended consolidation treatment phase compared to 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 compared to two conventional highly intensive chemotherapy courses?
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Timepoint(s) of evaluation of this end point: EFS and DFS time: end of study

Primary end point(s): For the randomized study questions, the primary endpoint will be the time from randomization until the first event defined as follows:
Randomization R-eHR, R-HR and R-T: 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.
Randomization R-MR: Relapse, second malignancy or death from any cause. This will be called DFS time.

Secondary Objective: - 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?
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Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Survival, treatment-related mortality, AE and SAE: end of study
MRD related endpoints: after the repective MRD evaluation of the last patient in study

Secondary end point(s): - Survival starting at the same time point as the EFS/DFS
- Frequency and incidence of treatment-related mortality in induction or CCR
- Frequency and incidence of AE of interest and SAE in specific protocol phases, randomized arms and overall during follow-up
- MRD load after the randomized treatment phases (R-eHR, R-HR, R-MR and R-T)
- MRD load after the first/second cycle of Blinatumomab or after the HR 2’/HR 3’ block (R-HR)
- Proportion of patients with poor MRD response to the first Blinatumomab cycle (“Blinatumomab Poor-Response”) (R HR)

Secondary ID(s)

AIEOP-BFM_ALL_2017

2016-001935-12-DE

Source(s) of Monetary Support

Deutsche Krebshilfe

Ethics review

Status: Approved
Approval date: 31/08/2018
Contact: