International Study for Treatment of High Risk Childhood Relapsed ALL 2010
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ClinicalTrials.gov Identifier: NCT03590171 |
Recruitment Status :
Recruiting
First Posted : July 18, 2018
Last Update Posted : August 17, 2020
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Condition or disease | Intervention/treatment | Phase |
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Acute Lymphoblastic Leukemia (ALL) | Drug: Bortezomib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 250 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | September 1, 2017 |
Estimated Primary Completion Date : | August 2023 |
Estimated Study Completion Date : | August 2023 |

Arm | Intervention/treatment |
---|---|
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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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. |
- 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).
- Event-free Survival [ Time Frame: Year 3 ]Improvement of three years event-free survival (EFS)
- Overall Survival [ Time Frame: Year 3 ]Improvement of three years overall survival (OS)
- Minimal Residual Disease Reduction (MRD) [ Time Frame: Week 4 ]Improvement of Minimal Residual Disease (MRD) reduction after induction with versus without bortezomib
- Minimal Residual Disease Load [ Time Frame: Week 15 ]Improvement of MRD load prior to stem cell transplantation (SCT).
- 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.
- Complete Remission/Minimal Residual Disease Rates During Consolidation [ Time Frame: Week 5, 8, 11, 15 ]Improvement of CR2 and/or MRD rates during consolidation
- 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).
- 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.
- Extended Genetic Characterization [ Time Frame: Day 0 ]Extension of genetic characterization and correlation with clinical data
- 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.

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Ages Eligible for Study: | up to 17 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03590171
Contact: Arend von Stackelberg, MD | +49(0)30-450666 ext 833 | arend.stackelberg@charite.de |
Australia, Victoria | |
Australian & New Zealand Childhood Hematology & Oncology Group | Recruiting |
Clayton, Victoria, Australia, 3168 | |
Contact: Tamas Revesz, MD | |
Austria | |
St. Anna Kinderkrebsforschung, CCRI | Recruiting |
Vienna, Austria, 1090 | |
Contact: Georg Mann, MD | |
Contact: Andishe Atterbashi, MD | |
Belgium | |
Hòpital Universitaire des Enfants Reine Fabiola | Recruiting |
Bruxelles, Belgium, 1020 | |
Contact: Alina Ferster, MD | |
Czechia | |
University Hospital Motol | Recruiting |
Prague, Czechia | |
Contact: Lucie Sramkova, MD | |
Denmark | |
Copenhagen University Hospital (Rigshospitalet) | Not yet recruiting |
Copenhagen, Denmark, 2100 | |
Contact: Thomas Frandsen, MD | |
Finland | |
Turku University Central Hospital | Recruiting |
Turku, Finland, SF-20520 | |
Contact: Päivi Lähteenmäki, MD | |
France | |
CHU Nice | Recruiting |
Nice, France | |
Contact: Pierre Rohrlich, MD | |
Israel | |
Tel Aviv Sourasky Medical Centre | Recruiting |
Tel Aviv, Israel, 64239 | |
Contact: Ronit Elhasid, MD | |
Italy | |
Ospedale Pediatrico Bambino Gesù | Recruiting |
Roma, Italy, 00165 | |
Contact: Franco Locatelli, MD | |
Netherlands | |
Prinses Máxima Centrum, Lundlaan | Recruiting |
Utrecht, Netherlands | |
Contact: Peter Hoogerbrugge, MD | |
Norway | |
Oslo University Hospital | Not yet recruiting |
Oslo, Norway, 0027 | |
Contact: Marit Hellebostad, MD | |
Poland | |
Dpt. SCT and Hematology/Oncology University Wroclaw | Recruiting |
Wroclaw, Poland, 50354 | |
Contact: Ewa Goczynska, MD | |
Portugal | |
Instituto Português de Oncologia de Lisboa | Not yet recruiting |
Lisboa, Portugal | |
Contact: Joaquin Duarte, MD | |
Sweden | |
University Hospital Stockholm | Not yet recruiting |
Stockholm, Sweden, 17176 | |
Contact: Petter Svenberg, MD | |
United Kingdom | |
Royal Manchester Children's Hospital | Not yet recruiting |
Manchester, United Kingdom, M13 9WL | |
Contact: Denise Bonney, MD |
Principal Investigator: | Arend von Stackelberg, MD | Charite University, Berlin, Germany |
Responsible Party: | PD Dr. Arend von Stackelberg, Prinicipal Investigator, Charite University, Berlin, Germany |
ClinicalTrials.gov Identifier: | NCT03590171 |
Other Study ID Numbers: |
IntReALL HR 2010 |
First Posted: | July 18, 2018 Key Record Dates |
Last Update Posted: | August 17, 2020 |
Last Verified: | August 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
ALL |
Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Bortezomib Antineoplastic Agents |