IntReALL HR 2010 |
IntReALL HR 2010 – International Study for Treatment of High Risk Childhood Relapsed ALL 2010 |
Disease |
Relapsed ALL |
Type |
inter-group, international multi-centre, randomized treatment optimization trial. |
Rationale / Objectives |
Primary objectives
To improve rates of complete remission (CR) in HR ALL relapse patients
Secondary objectives:
To improve rates of event-free survival (EFS) and overall survival (OS)
To improve MRD reduction after induction with versus without bortezomib
To evaluate toxicity of induction with versus without bortezomib
To evaluate efficacy of consolidation elements regarding reduction of MRD burden before allogeneic HSCT
|
Therapy / Study arms |
The IntReALL HR 2010 study is an international multicentre, unblinded, randomised therapy optimising trial.
It includes the following treatment arms:
- Induction: prospective, adaptive, unblinded randomized phase II study comparing arm A (modified ALL R3 protocol) with arm B (modified ALL R3 protocol + bortezomib)
- Post-induction: Single-arm post-induction observational study with intensive polychemotherapy with the blocks HC1 (modified AIEOP-BFM ALL 2009 HR1 block) and HC2 (modified HR3 block).
- NEW September 2019: 3rd post-induction block: as the interim analysis of the Amgen Blinatumomab study showed superiority of the Blinatumomab cycle over the HC3 block, the study was terminated early and all patients can receive the Blinatumomab cycle.
- All patients in morphologically complete 2nd remission will undergo allogeneic HSCT.
- Termination of the study after completion of the second or third consolidation block prior to the investigational window study and/or allo-HSCT. Follow-up will continue until the secondary EFS/OS endpoints are reached
- Patients with an inadequate response to therapy (MRD ≥ 10-3 after induction) may receive individualized consolidation therapy based on individual biological characteristics of the leukemia (if such treatment is available)
|
Inclusion Criteria |
- Morphologically confirmed diagnosis of first relapsed precursor B-cell or T-cell ALL
- Children under 18 years of age at date of inclusion into the study
- Meeting all HR criteria
- Patient enrolled in a participating study centre
- Written informed consent
- Start of treatment falling into the study period
- No participation in other clinical trials 30 days prior to study enrolment that interfere with this protocol, except trials for primary ALL
|
Exclusion Criteria |
- BCR-ABL/ t(9;22) positive ALL
- Pregnancy or positive pregnancy test (urine sample positive for β-HCG over 10 U/l)
- Sexually active adolescents who do not consent to the use of highly effective contraception (Pearl Index under 1) until 12 months after the end of anti-leukaemic therapy
- Breastfeeding
- Recurrence after allogeneic HSCT
- Neuropathy higher II°
- Refusal of the entire protocol or essential parts by the patient himself/herself, his/her parents or legal guardian
- No consent for saving and propagation of pseudonymized medical data for study reasons
- Severe concomitant disease that, at the investigator's discretion, does not allow treatment according to the protocol (e.g. malformation syndromes, cardiac malformations, metabolic disorders)
- Patients who are unwilling or unable to comply with the study procedures
- Subjects who are legally detained in an official institute
|
Recruitment |
300 |
Status |
Start 01/12/2018, End: after reaching the necessary number of patients |
EudraCT |
2012-000810-12
|
Entry Study Register |
|
Principal Investigator |
PD Dr. med. Arend v. Stackelberg |
E-Mail |
allrez@charite.de
|
Contact |
Principal Investigator
PD Dr. med.
Arend von Stackelberg
Charité, Campus Virchow-Klinikum
Klinik f. Pädiatrie m. S. Onkologie und Hämatologie
Augustenburger Platz 1
13353
Berlin
Telefon +49 (30) 450 566833
Fax +49 (30) 450 566901
arend.stackelberg@charite.de
Trial Coordinator
Dr.
Christiane Chen-Santel
Charité, Campus Virchow-Klinikum
Klinik für Pädiatrie m. S. Onkologie und Hämatologie
Augustenburger Platz 1
13353
Berlin
Telefon +49 (251) 83 52833
christiane.chen-santel@charite.de
Andrej Lissat
Charité - Universitätsmedizin Berlin
Pädiatrische klinik m. S. Onkologie/ Hämatologie, ALL-REZ Studien
Augustenburger Platz 1
13353
Berlin
Telefon +49 (30) 450 566 074
Fax +49 (30) 450 566 901
andrej.lissat@charite.de
Trial managing
Dr. rer. medic.
Adriane Napp
Charité-Universitätsmedizin Berlin
Päd. Klinuik m. S. Onkologie/Hämatologie
Augustenburger Platz 1
13353
Berlin
Telefon +49 (30) 450666 829
Fax +49 (30) 450 756 6829
loggic-register@charite.de
Trial Center Germany
Andrea Kretschmann
Charité, Campus Virchow-Klinikum
ALL-REZ Studienzentrale, Klinik für Pädiatrie m.S.Onkologie und Hämatologie
Augustenburger Platz 1
13353
Berlin
Telefon +49 (30) 450 566 354
Fax +49 (30) 450 566 901
andrea.kretschmann@charite.de
Julia Dobke
Charité Universitätsmedizin Berlin
Pädiatrische Klinik m. S. Onkologie, Hämatologie und SZT
Augustenburger Platz 1
13353
Berlin
Telefon +49 (30) 450 566 354
Fax +49 (30) 450 566 901
julia.dobke@charite.de
|
Participants |
Germany, Austria, Switzerland, Australia, New Zealand, Belgium, Czech Republic, Denmark, Finland, France, Ireland, Israel, Italy, the Netherlands, Norway, Poland, Portugal, Sweden, Spain |
Weitere Informationen |
Sponsor: Charité Universitätsmedizin Berlin |
Sponsoring |
Deutsche Kinderkrebstiftung, FP7 |