Acute Lymphoblastic Leukemia (ALL)Phase 2NCT03590171
International Study for Treatment of High Risk Childhood Relapsed ALL 2010
A Phase 2 study testing Bortezomib in people with Acute Lymphoblastic Leukemia (ALL), run by Charite University, Berlin, Germany at 15 sites in 15 countries.
Trial summary
The main goal of this study is to improve the outcome of children and adolescents with acute lymphoblastic leukemia with high risk first relapse by optimization of treatment strategies within a large international trial and the integration of new agents. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia (ALL)
- What is being tested?
- Bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 15 sitesin 15 countries
- Study dates
- 1 Sep 2017to 31 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- Breakpoint cluster region-Abelson (BCR-ABL)/ t(9;22) positive ALL
- Pregnancy or positive pregnancy test (urine sample positive for β-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°
Show all 13Show fewer
- 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
Trial locations and contacts
15 sites in 15 countries. Contact the study team or a site near you to ask about taking part.
15 sites in 15 countries
Australia1 site, 1 recruiting
- Recruiting
Australian & New Zealand Childhood Hematology & Oncology Group
Clayton, Victoria, 3168
Tamas Revesz, MD
Austria1 site, 1 recruiting
- Recruiting
St. Anna Kinderkrebsforschung, CCRI
Vienna, 1090
Georg Mann, MD
Andishe Atterbashi, MD
Belgium1 site, 1 recruiting
- Recruiting
Hòpital Universitaire des Enfants Reine Fabiola
Brussels, 1020
Alina Ferster, MD
Czechia1 site, 1 recruiting
- Recruiting
University Hospital Motol
Prague
Lucie Sramkova, MD
Denmark1 site, 1 recruiting
- Not yet recruiting
Copenhagen University Hospital (Rigshospitalet)
Copenhagen, 2100
Thomas Frandsen, MD
Finland1 site, 1 recruiting
- Recruiting
Turku University Central Hospital
Turku, SF-20520
Päivi Lähteenmäki, MD
Israel1 site, 1 recruiting
- Recruiting
Tel Aviv Sourasky Medical Centre
Tel Aviv, 64239
Ronit Elhasid, MD
Italy1 site, 1 recruiting
- Recruiting
Ospedale Pediatrico Bambino Gesù
Roma, 00165
Franco Locatelli, MD
Netherlands1 site, 1 recruiting
- Recruiting
Prinses Máxima Centrum, Lundlaan
Utrecht
Peter Hoogerbrugge, MD
Norway1 site, 1 recruiting
- Not yet recruiting
Oslo University Hospital
Oslo, 0027
Marit Hellebostad, MD
Poland1 site, 1 recruiting
- Recruiting
Dpt. SCT and Hematology/Oncology University Wroclaw
Wroclaw, 50354
Ewa Goczynska, MD
Portugal1 site, 1 recruiting
- Not yet recruiting
Instituto Português de Oncologia de Lisboa
Lisbon
Joaquin Duarte, MD
Sweden1 site, 1 recruiting
- Not yet recruiting
University Hospital Stockholm
Stockholm, 17176
Petter Svenberg, MD
United Kingdom1 site, 1 recruiting
- Not yet recruiting
Royal Manchester Children's Hospital
Manchester, M13 9WL
Denise Bonney, MD
About this study
Official 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
The main goal of this study is to improve the outcome of children and adolescents with acute lymphoblastic leukemia with high risk first relapse by optimization of treatment strategies within a large international trial and the integration of new agents.
Read the detailed description
Though survival of children with acute lymphoblastic leukemia (ALL) has considerably improved over the past few decades, relapsed ALL remains a leading cause of mortality in children with cancer. Risk has been defined by the International (I) Berlin, Frankfurt, Münster (BFM) Study Group (SG) based on duration of first remission, immunophenotype of malignant clone, and site of relapse. Patients classified as high risk (HR) by these criteria have poor response rates to standard induction therapy, high rates of subsequent relapse and require an allogeneic hematopoetic stem cell transplantation (allo-HSCT) for consolidation of 2nd remission. Over the last decade members of the I-BFM-SG have investigated the use of different combinations of conventional cytotoxic agents. Even with allo-HSCT, none of these approaches have improved outcome above 40%. Therefore, for HR patients there is a need to investigate the curative potential of new agents combined with systemic therapy. The proteasome inhibitor bortezomib has shown synergistic activity with acceptable toxicity when combined with corticosteroids, anthracyclines and alkylating agents in adult patients with cancer as well as with dexamethasone, doxorubicin, vincristine and polyethylene glycol (PEG) asparaginase in children with refractory or relapsed ALL. In the I-BFM-SG International Study for Treatment of High Risk Childhood Relapsed ALL (IntReALL) HR 2010 study, the potential of Bortezomib combined with a modified ALL relapse protocol 3 (R3) backbone as induction regimen for HR patients to improve complete 2nd remission (CR2) rates will be investigated in a randomized phase II design. Induction is followed by conventional intensive consolidation. After termination of the trial patients may be subjected to an investigational window, before all of them receive allo-HSCT.
- Conditions
- Acute Lymphoblastic Leukemia (ALL)
- Being tested
- Bortezomib
- Keywords
- ALL
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm HR-A | No intervention | Induction: Backbone ALL R3 |
| Arm HR-B | Experimental | Induction: Backbone ALL R3 + Bortezomib Receives: Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Complete Remission
Rate of complete second remission (CR2) quantified by cytology after induction with standard chemotherapy + bortezomib (arm B) compared with standard chemotherapy (arm A).
Measured: Week 4
Secondary outcomes (7)
Event-free Survival
Improvement of three years event-free survival (EFS)
Measured: Year 3
Overall Survival
Improvement of three years overall survival (OS)
Measured: Year 3
Minimal Residual Disease Reduction (MRD)
Improvement of Minimal Residual Disease (MRD) reduction after induction with versus without bortezomib
Measured: Week 4
Minimal Residual Disease Load
Improvement of MRD load prior to stem cell transplantation (SCT).
Measured: Week 15
Minimal Residual Disease (MRD)
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.
Measured: Week 15
Complete Remission/Minimal Residual Disease Rates During Consolidation
Improvement of CR2 and/or MRD rates during consolidation
Measured: Week 5, 8, 11, 15
Toxicity of induction classified with the COMMON TOXICITY CRITERIA (CTC)
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).
Measured: At induction up to week 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2018
- Study start1 Sep 2017
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic Leukemia (ALL)Studies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- Australian & New Zealand Children's Haematology/Oncology Group, St. Anna Kinderkrebsforschung, CCRI (co-sponsor, Austria), European Organisation for Research and Treatment of Cancer - EORTC, University Hospital, Motol, Copenhagen University Hospital, Rigshospitalet, Turku University Central Hospital (co-sponsor, Finland), Centre Hospitalier Universitaire de Nice, Our Lady's Chilrden's Hospital (Co-Sponsor Ireland), Tel Aviv Sourasky Medical Centre (Co-Sponsor Israel), Ospedale Pediatrico Bambino (co-sponsor, Italy), Prinses Máxima Centrum (Co-Sponsor Netherlands), Oslo University Hospital (co-sponsor, Norway), Wroclaw Medical University, Instituto Português de Oncologia de Lisboa (co-sponsor, Portugal), Karolinska University Hospital Stockholm (co-sponsor, Sweden), Spanish Society of Pediatric Hematology and Oncology (SEHOP) (Co-Sponsor Spain), University Children's Hospital, Zurich, Manchester University NHS Foundation Trust
- Responsible party
- Principal investigator, PD Dr. Arend von Stackelberg, Charite University, Berlin, Germany
- Investigators
- Arend von Stackelberg, MD, Principal investigator, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03590171
- Sponsor's protocol ID
- IntReALL HR 2010
- Status last verified
- Mar 2026
- First submitted
- 23 May 2018
- Last updated
- 17 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03590171
- Acronym / sponsor ID
- IntReALL HR 2010
- Conditions
- Acute Lymphoblastic Leukemia (ALL)
- Keywords
- ALL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Collaborators
- Australian & New Zealand Children's Haematology/Oncology Group, St. Anna Kinderkrebsforschung, CCRI (co-sponsor, Austria), European Organisation for Research and Treatment of Cancer - EORTC, University Hospital, Motol, Copenhagen University Hospital, Rigshospitalet, Turku University Central Hospital (co-sponsor, Finland), Centre Hospitalier Universitaire de Nice, Our Lady's Chilrden's Hospital (Co-Sponsor Ireland), Tel Aviv Sourasky Medical Centre (Co-Sponsor Israel), Ospedale Pediatrico Bambino (co-sponsor, Italy), Prinses Máxima Centrum (Co-Sponsor Netherlands), Oslo University Hospital (co-sponsor, Norway), Wroclaw Medical University, Instituto Português de Oncologia de Lisboa (co-sponsor, Portugal), Karolinska University Hospital Stockholm (co-sponsor, Sweden), Spanish Society of Pediatric Hematology and Oncology (SEHOP) (Co-Sponsor Spain), University Children's Hospital, Zurich, Manchester University NHS Foundation Trust
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 18 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main goal of this study is to improve the outcome of children and adolescents with acute lymphoblastic leukemia with high risk first relapse by optimization of treatment strategies within a large international trial and the integration of new agents.
Detailed description
Though survival of children with acute lymphoblastic leukemia (ALL) has considerably improved over the past few decades, relapsed ALL remains a leading cause of mortality in children with cancer. Risk has been defined by the International (I) Berlin, Frankfurt, Münster (BFM) Study Group (SG) based on duration of first remission, immunophenotype of malignant clone, and site of relapse. Patients classified as high risk (HR) by these criteria have poor response rates to standard induction therapy, high rates of subsequent relapse and require an allogeneic hematopoetic stem cell transplantation (allo-HSCT) for consolidation of 2nd remission. Over the last decade members of the I-BFM-SG have investigated the use of different combinations of conventional cytotoxic agents. Even with allo-HSCT, none of these approaches have improved outcome above 40%. Therefore, for HR patients there is a need to investigate the curative potential of new agents combined with systemic therapy. The proteasome inhibitor bortezomib has shown synergistic activity with acceptable toxicity when combined with corticosteroids, anthracyclines and alkylating agents in adult patients with cancer as well as with dexamethasone, doxorubicin, vincristine and polyethylene glycol (PEG) asparaginase in children with refractory or relapsed ALL. In the I-BFM-SG International Study for Treatment of High Risk Childhood Relapsed ALL (IntReALL) HR 2010 study, the potential of Bortezomib combined with a modified ALL relapse protocol 3 (R3) backbone as induction regimen for HR patients to improve complete 2nd remission (CR2) rates will be investigated in a randomized phase II design. Induction is followed by conventional intensive consolidation. After termination of the trial patients may be subjected to an investigational window, before all of them receive allo-HSCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm HR-A | No intervention | –Induction: Backbone ALL R3 |
| Arm HR-B | Experimental | Drug: BortezomibInduction: Backbone ALL R3 + Bortezomib |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- Breakpoint cluster region-Abelson (BCR-ABL)/ t(9;22) positive ALL
- Pregnancy or positive pregnancy test (urine sample positive for β-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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibPatients 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. | Drug | Arm HR-B |
Primary outcome
Rate of Complete Remission
Time frame: Week 4
Rate of complete second remission (CR2) quantified by cytology after induction with standard chemotherapy + bortezomib (arm B) compared with standard chemotherapy (arm A).
7 secondary outcomes
Event-free Survival
Time frame: Year 3
Overall Survival
Time frame: Year 3
Minimal Residual Disease Reduction (MRD)
Time frame: Week 4
Minimal Residual Disease Load
Time frame: Week 15
Minimal Residual Disease (MRD)
Time frame: Week 15
Complete Remission/Minimal Residual Disease Rates During Consolidation
Time frame: Week 5, 8, 11, 15
Toxicity of induction classified with the COMMON TOXICITY CRITERIA (CTC)
Time frame: At induction up to week 5
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Arend von Stackelberg, MD principal investigator
Charite University, Berlin, Germany
15 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib in people with Acute Lymphoblastic Leukemia (ALL), run by Charite University, Berlin, Germany at 15 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Australia, Austria, Belgium, Czechia, Denmark and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Arend von Stackelberg, MD (+49(0)30-450666 ext. 833, arend.stackelberg@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Complete Remission (time frame: Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2026.