International Study for Treatment of High Risk Childhood Relapsed ALL 2010

March 16, 2026 updated by: PD Dr. Arend von Stackelberg, Charite University, Berlin, Germany

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
250

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Recruiting
        • Australian & New Zealand Childhood Hematology & Oncology Group
        • Contact:
          • Tamas Revesz, MD
  • Austria
      • Vienna, Austria, 1090
        • Recruiting
        • St. Anna Kinderkrebsforschung, CCRI
        • Contact:
          • Georg Mann, MD
        • Contact:
          • Andishe Atterbashi, MD
  • Belgium
      • Brussels, Belgium, 1020
        • Recruiting
        • Hopital Universitaire des Enfants Reine Fabiola
        • Contact:
          • Alina Ferster, MD
  • Czechia
      • Prague, Czechia
        • Recruiting
        • University Hospital Motol
        • Contact:
          • Lucie Sramkova, MD
  • Denmark
      • Copenhagen, Denmark, 2100
        • Not yet recruiting
        • Copenhagen University Hospital (Rigshospitalet)
        • Contact:
          • Thomas Frandsen, MD
  • Finland
      • Turku, Finland, SF-20520
        • Recruiting
        • Turku University Central Hospital
        • Contact:
          • Päivi Lähteenmäki, MD
  • France
      • Nice, France
        • Recruiting
        • CHU Nice
        • Contact:
          • Pierre Rohrlich, MD
  • Israel
      • Tel Aviv, Israel, 64239
        • Recruiting
        • Tel Aviv Sourasky Medical Centre
        • Contact:
          • Ronit Elhasid, MD
  • Italy
      • Roma, Italy, 00165
        • Recruiting
        • Ospedale Pediatrico Bambino Gesu
        • Contact:
          • Franco Locatelli, MD
  • Netherlands
      • Utrecht, Netherlands
        • Recruiting
        • Prinses Máxima Centrum, Lundlaan
        • Contact:
          • Peter Hoogerbrugge, MD
  • Norway
      • Oslo, Norway, 0027
        • Not yet recruiting
        • Oslo University Hospital
        • Contact:
          • Marit Hellebostad, MD
  • Poland
      • Wroclaw, Poland, 50354
        • Recruiting
        • Dpt. SCT and Hematology/Oncology University Wroclaw
        • Contact:
          • Ewa Goczynska, MD
  • Portugal
      • Lisbon, Portugal
        • Not yet recruiting
        • Instituto Português de Oncologia de Lisboa
        • Contact:
          • Joaquin Duarte, MD
  • Sweden
      • Stockholm, Sweden, 17176
        • Not yet recruiting
        • University Hospital Stockholm
        • Contact:
          • Petter Svenberg, MD
  • United Kingdom
      • Manchester, United Kingdom, M13 9WL
        • Not yet recruiting
        • Royal Manchester Children's Hospital
        • Contact:
          • Denise Bonney, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 17 years (Child)

Accepts Healthy Volunteers

No

Description

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

Exclusion Criteria:

  • 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°
  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Arm HR-A
Induction: Backbone ALL R3
Experimental: Arm HR-B
Induction: Backbone ALL R3 + Bortezomib
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
Week 4

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Event-free Survival
Time Frame: Year 3
Improvement of three years event-free survival (EFS)
Year 3
Overall Survival
Time Frame: Year 3
Improvement of three years overall survival (OS)
Year 3
Minimal Residual Disease Reduction (MRD)
Time Frame: Week 4
Improvement of Minimal Residual Disease (MRD) reduction after induction with versus without bortezomib
Week 4
Minimal Residual Disease Load
Time Frame: Week 15
Improvement of MRD load prior to stem cell transplantation (SCT).
Week 15
Minimal Residual Disease (MRD)
Time Frame: Week 15
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.
Week 15
Complete Remission/Minimal Residual Disease Rates During Consolidation
Time Frame: Week 5, 8, 11, 15
Improvement of CR2 and/or MRD rates during consolidation
Week 5, 8, 11, 15
Toxicity of induction classified with the COMMON TOXICITY CRITERIA (CTC)
Time Frame: At induction up to week 5
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).
At induction up to week 5

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Minimal Residual Disease in Isolated Extramedullary Relapse
Time Frame: Day 0; Week 5, 8, 11, 15
The rate and extent of sub-microscopic bone marrow (BM) involvement in extramedullary leukemia will be investigated prospectively.
Day 0; Week 5, 8, 11, 15
Extended Genetic Characterization
Time Frame: Day 0
Extension of genetic characterization and correlation with clinical data
Day 0
In-vitro drug response profile
Time Frame: Day 0
Generation of primografts from patient samples for bio-banking and drug testing by using immunodeficient mice. The outcome measure is the in-vitro drug response profile using the primograft of primary patient sample. The in-vitro drug response profile will be compared to the in-vivo drug response of a patient. In order to get an "in-vitro drug response profile" apoptosis/viability of the primary patient sample or patient-derived xenograft sample is measured using different concentrations of novel drugs normally after 48 hours of treatment. These drugs could be potentially given to a patient, when there will be no response to conventional protocol treatment. Apoptosis/viability is measured by live cell imaging microscopy or/and by flow cytometry. The report will include half maximal inhibitory concentration (IC50), the concentration of a drug which kills half of the cell after a defined time (normally 48h) for a variety of potential drugs.
Day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Charite University, Berlin, Germany

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Rigshospitalet, Denmark
European Organisation for Research and Treatment of Cancer - EORTC
Centre Hospitalier Universitaire de Nice
University Children's Hospital, Zurich
Australian & New Zealand Children's Haematology/Oncology Group
St. Anna Kinderkrebsforschung, CCRI (co-sponsor, Austria)
Turku University Central Hospital (co-sponsor, Finland)
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)
Medical University of Wroclaw (Co-Sponsor Poland)
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)
Central Manchester University Hospitals NHS Foundation Trust (co-sponsor, UK)
University Hospital, Motol

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Arend von Stackelberg, MD, Charite University, Berlin, Germany

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2017

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 23, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 18, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IntReALL HR 2010

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Lymphoblastic Leukemia (ALL)

Clinical Trials on Bortezomib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings