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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03590171




Registration number
NCT03590171
Ethics application status
Date submitted
23/05/2018
Date registered
18/07/2018
Date last updated
9/02/2024

Titles & IDs
Public title
International Study for Treatment of High Risk Childhood Relapsed ALL 2010
Scientific title
International Study for Treatment of High Risk Childhood Relapsed ALL 2010 A Randomized Phase II Study Conducted by the Resistant Disease Committee of the International Berlin, Frankfurt, Münster (BFM) Study Group
Secondary ID [1] 0 0
IntReALL HR 2010
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia (ALL) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bortezomib

No intervention: Arm HR-A - Induction: Backbone ALL R3

Experimental: Arm HR-B - Induction: Backbone ALL R3 + Bortezomib


Treatment: Drugs: Bortezomib
Patients randomised to the HR-B arm receive induction, consolidation with the modified ALL R3 protocol. In this arm, patients are randomized to receive Bortezomib together with the ALL R3 protocol during induction. Administration of Bortezomib: 1.3 mg/m2 as intravenous bolus or subcutaneously (SC, at the discretion of the treating physician) on days 1 and 4 of weeks 1 and 3.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of Complete Remission
Assessment method [1] 0 0
Rate of complete second remission (CR2) quantified by cytology after induction with standard chemotherapy + bortezomib (arm B) compared with standard chemotherapy (arm A).
Timepoint [1] 0 0
Week 4
Secondary outcome [1] 0 0
Event-free Survival
Assessment method [1] 0 0
Improvement of three years event-free survival (EFS)
Timepoint [1] 0 0
Year 3
Secondary outcome [2] 0 0
Overall Survival
Assessment method [2] 0 0
Improvement of three years overall survival (OS)
Timepoint [2] 0 0
Year 3
Secondary outcome [3] 0 0
Minimal Residual Disease Reduction (MRD)
Assessment method [3] 0 0
Improvement of Minimal Residual Disease (MRD) reduction after induction with versus without bortezomib
Timepoint [3] 0 0
Week 4
Secondary outcome [4] 0 0
Minimal Residual Disease Load
Assessment method [4] 0 0
Improvement of MRD load prior to stem cell transplantation (SCT).
Timepoint [4] 0 0
Week 15
Secondary outcome [5] 0 0
Minimal Residual Disease (MRD)
Assessment method [5] 0 0
Prognostic relevance of MRD pre stem cell transplantation (SCT). MRD will be quantified before stem cell transplantation with polymerase chain reaction (PCR) and will be related to EFS after SCT. Multicolour flow cytometry will be used in parallel with PCR. Flow cytometry is used instead of PCR if PCR based MRD-quantification cannot be performed, because criteria for a reliable and reproducible sensitive quantification are not fulfilled.
Timepoint [5] 0 0
Week 15
Secondary outcome [6] 0 0
Complete Remission/Minimal Residual Disease Rates During Consolidation
Assessment method [6] 0 0
Improvement of CR2 and/or MRD rates during consolidation
Timepoint [6] 0 0
Week 5, 8, 11, 15
Secondary outcome [7] 0 0
Toxicity of induction classified with the COMMON TOXICITY CRITERIA (CTC)
Assessment method [7] 0 0
Toxicity of induction with versus without bortezomib. Toxicity of the central nervous system and peripheral neuropathy will be classified with the COMMON TOXICITY CRITERIA (CTC).
Timepoint [7] 0 0
At induction up to week 5

Eligibility
Key inclusion criteria
* Morphologically confirmed diagnosis of 1st relapsed precursor B-cell or T-cell ALL
* Children less than 18 years of age at date of inclusion into the study
* Meeting HR criteria any BM relapse, early/very early isolated BM relapse, very early isolated/combined extramedullary relapse)
* Patient enrolled in a participating centre
* Written informed consent
* Start of treatment falling into the study period
* No participation in other clinical trials 30 day prior to study enrolment that interfere with this protocol, except trials for primary ALL
Minimum age
No limit
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Breakpoint cluster region-Abelson (BCR-ABL)/ t(9;22) positive ALL
* Pregnancy or positive pregnancy test (urine sample positive for ß-humane choriongonadotropin (HCG) > 10 U/l)
* Sexually active adolescents not willing to use highly effective contraceptive method (pearl index <1) until 12 months after end of anti-leukemic therapy
* Breast feeding
* Relapse post allogeneic stem-cell transplantation
* Neuropathy > II°
* The whole protocol or essential parts are declined either by patient himself/herself or the respective legal guardian
* Objection to the study participation by a minor patient, able to object
* Any patient being dependent on the investigator
* No consent is given for saving and propagation of pseudonymized medical data for study reasons
* Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion (e.g. malformation syndromes, cardiac malformations, metabolic disorders)
* Subjects unwilling or unable to comply with the study procedures
* Subjects who are legally detained in an official institute

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
250
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Australian & New Zealand Childhood Hematology & Oncology Group - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Vienna
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Czechia
State/province [3] 0 0
Prague
Country [4] 0 0
Denmark
State/province [4] 0 0
Copenhagen
Country [5] 0 0
Finland
State/province [5] 0 0
Turku
Country [6] 0 0
France
State/province [6] 0 0
Nice
Country [7] 0 0
Israel
State/province [7] 0 0
Tel Aviv
Country [8] 0 0
Italy
State/province [8] 0 0
Roma
Country [9] 0 0
Netherlands
State/province [9] 0 0
Utrecht
Country [10] 0 0
Norway
State/province [10] 0 0
Oslo
Country [11] 0 0
Poland
State/province [11] 0 0
Wroclaw
Country [12] 0 0
Portugal
State/province [12] 0 0
Lisboa
Country [13] 0 0
Sweden
State/province [13] 0 0
Stockholm
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Other
Name
Charite University, Berlin, Germany
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australian & New Zealand Children's Haematology/Oncology Group
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
St. Anna Kinderkrebsforschung, CCRI (co-sponsor, Austria)
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University Hospital Motol (Co-Sponsor Czech Republic)
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Copenhagen University Hospital, Rigshospitalet (co-sponsor, Denmark)
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Turku University Central Hospital (co-sponsor, Finland)
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Centre Hospitalier Universitaire de Nice
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
Our Lady's Chilrden's Hospital (Co-Sponsor Ireland)
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
Tel Aviv Sourasky Medical Centre (Co-Sponsor Israel)
Country [9] 0 0
Other collaborator category [10] 0 0
Other
Name [10] 0 0
Ospedale Pediatrico Bambino (co-sponsor, Italy)
Country [10] 0 0
Other collaborator category [11] 0 0
Other
Name [11] 0 0
Prinses Máxima Centrum (Co-Sponsor Netherlands)
Country [11] 0 0
Other collaborator category [12] 0 0
Other
Name [12] 0 0
Oslo University Hospital (co-sponsor, Norway)
Country [12] 0 0
Other collaborator category [13] 0 0
Other
Name [13] 0 0
Medical University of Wroclaw (Co-Sponsor Poland)
Country [13] 0 0
Other collaborator category [14] 0 0
Other
Name [14] 0 0
Instituto Português de Oncologia de Lisboa (co-sponsor, Portugal)
Country [14] 0 0
Other collaborator category [15] 0 0
Other
Name [15] 0 0
Karolinska University Hospital Stockholm (co-sponsor, Sweden)
Country [15] 0 0
Other collaborator category [16] 0 0
Other
Name [16] 0 0
Spanish Society of Pediatric Hematology and Oncology (SEHOP) (Co-Sponsor Spain)
Country [16] 0 0
Other collaborator category [17] 0 0
Other
Name [17] 0 0
University Children's Hospital, Zurich
Country [17] 0 0
Other collaborator category [18] 0 0
Other
Name [18] 0 0
Central Manchester University Hospitals NHS Foundation Trust (co-sponsor, UK)
Country [18] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Arend von Stackelberg, MD
Address 0 0
Charite University, Berlin, Germany
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Arend von Stackelberg, MD
Address 0 0
Country 0 0
Phone 0 0
+49(0)30-450666
Email 0 0
arend.stackelberg@charite.de
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT03590171