- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03590171
International Study for Treatment of High Risk Childhood Relapsed ALL 2010
February 8, 2024 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
Recruiting
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Estimated)
250
Phase
- 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
- Name: Arend von Stackelberg, MD
- Phone Number: 833 +49(0)30-450666
- Email: arend.stackelberg@charite.de
Study Locations
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Victoria
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Clayton, Victoria, Australia, 3168
- Recruiting
- Australian & New Zealand Childhood Hematology & Oncology Group
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Contact:
- Tamas Revesz, MD
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Vienna, Austria, 1090
- Recruiting
- St. Anna Kinderkrebsforschung, CCRI
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Contact:
- Georg Mann, MD
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Contact:
- Andishe Atterbashi, MD
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Bruxelles, Belgium, 1020
- Recruiting
- Hôpital Universitaire des Enfants Reine Fabiola
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Contact:
- Alina Ferster, MD
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Prague, Czechia
- Recruiting
- University Hospital Motol
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Contact:
- Lucie Sramkova, MD
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Copenhagen, Denmark, 2100
- Not yet recruiting
- Copenhagen University Hospital (Rigshospitalet)
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Contact:
- Thomas Frandsen, MD
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Turku, Finland, SF-20520
- Recruiting
- Turku University Central Hospital
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Contact:
- Päivi Lähteenmäki, MD
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Nice, France
- Recruiting
- CHU Nice
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Contact:
- Pierre Rohrlich, MD
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Tel Aviv, Israel, 64239
- Recruiting
- Tel Aviv Sourasky Medical Centre
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Contact:
- Ronit Elhasid, MD
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Roma, Italy, 00165
- Recruiting
- Ospedale Pediatrico Bambino Gesù
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Contact:
- Franco Locatelli, MD
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Utrecht, Netherlands
- Recruiting
- Prinses Máxima Centrum, Lundlaan
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Contact:
- Peter Hoogerbrugge, MD
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Oslo, Norway, 0027
- Not yet recruiting
- Oslo University Hospital
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Contact:
- Marit Hellebostad, MD
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Wroclaw, Poland, 50354
- Recruiting
- Dpt. SCT and Hematology/Oncology University Wroclaw
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Contact:
- Ewa Goczynska, MD
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Lisboa, Portugal
- Not yet recruiting
- Instituto Português de Oncologia de Lisboa
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Contact:
- Joaquin Duarte, MD
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Stockholm, Sweden, 17176
- Not yet recruiting
- University Hospital Stockholm
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Contact:
- Petter Svenberg, MD
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Manchester, United Kingdom, M13 9WL
- Not yet recruiting
- Royal Manchester Children's Hospital
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Contact:
- Denise Bonney, MD
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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
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 |
Intervention / Treatment |
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No Intervention: Arm HR-A
Induction: Backbone ALL R3
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Experimental: Arm HR-B
Induction: Backbone ALL R3 + Bortezomib
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of Complete Remission
Time Frame: Week 4
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Rate of complete second remission (CR2) quantified by cytology after induction with standard chemotherapy + bortezomib (arm B) compared with standard chemotherapy (arm A).
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Week 4
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Event-free Survival
Time Frame: Year 3
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Improvement of three years event-free survival (EFS)
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Year 3
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Overall Survival
Time Frame: Year 3
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Improvement of three years overall survival (OS)
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Year 3
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Minimal Residual Disease Reduction (MRD)
Time Frame: Week 4
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Improvement of Minimal Residual Disease (MRD) reduction after induction with versus without bortezomib
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Week 4
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Minimal Residual Disease Load
Time Frame: Week 15
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Improvement of MRD load prior to stem cell transplantation (SCT).
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Week 15
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Minimal Residual Disease (MRD)
Time Frame: Week 15
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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.
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Week 15
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Complete Remission/Minimal Residual Disease Rates During Consolidation
Time Frame: Week 5, 8, 11, 15
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Improvement of CR2 and/or MRD rates during consolidation
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Week 5, 8, 11, 15
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Toxicity of induction classified with the COMMON TOXICITY CRITERIA (CTC)
Time Frame: At induction up to week 5
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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).
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At induction up to week 5
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Minimal Residual Disease in Isolated Extramedullary Relapse
Time Frame: Day 0; Week 5, 8, 11, 15
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The rate and extent of sub-microscopic bone marrow (BM) involvement in extramedullary leukemia will be investigated prospectively.
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Day 0; Week 5, 8, 11, 15
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Extended Genetic Characterization
Time Frame: Day 0
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Extension of genetic characterization and correlation with clinical data
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Day 0
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In-vitro drug response profile
Time Frame: Day 0
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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.
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Day 0
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- 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)
September 1, 2017
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2027
Study Registration Dates
First Submitted
May 23, 2018
First Submitted That Met QC Criteria
July 17, 2018
First Posted (Actual)
July 18, 2018
Study Record Updates
Last Update Posted (Estimated)
February 9, 2024
Last Update Submitted That Met QC Criteria
February 8, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID 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.
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