Acute lymphoblastic leukemia (ALL) is the most frequent cancer in children and young adults with more than 70-80 new patients per year in Belgium (25% of all paediatric cancers).
In the last decades, the chances of cure for children and young adults with ALL have greatly improved, with a survival rate of more than 85-90%. Nevertheless, treatment efficacy remains insufficient for some of them, while others (40-50%) risk overtreatment, resulting in unnecessary, sometimes serious side effects. Under-and overtreatment can only be prevented if treatment effectiveness can be determined early on, leading to adjusting therapy to each individual patient.
With the ALLTogether consortium, in which a uniform European treatment protocol is developed, we aim for a less harmful, but equally effective therapy for low-risk patients on the one hand and, on the other hand, for an intensification of treatment for those with the highest risk of relapse through the addition of innovative therapy (inotuzumab) or combination therapy (TEAM). The purpose of this study is to create a Belgian framework for rolling out and harmonising this European treatment plan for best standard of care, with the ultimate aim of improving the survival and quality of survival for children and young adults with ALL in Belgium.
| Title | ALLTogether1– A Treatment study protocol of the ALLTogether Consortium for children and young adults (1-45 years of age) with newly diagnosed acute lymphoblastic leukaemia (ALL) |
| Participants (P) | Children and young adults with newly diagnosed T-lineage or precursor-B (BCP) acute lymphoblastic leukemia |
| Intervention (I) | R1: In low risk (SR) patients tests whether therapy can be safely reduced by the randomised omission of Doxorubicin in the Delayed Intensification phase of treatment R2: In intermediate risk (IR-Low) patients with a low risk of relapse (IR-low) with standard IR-therapy tests if the therapy may be safely reduced by the randomised omission of either Doxorubicin in the Delayed Intensification phase of treatment or the omission of Vincristine(VCR)/Dexamethasone(Dexa) pulses in the Maintenance phase of treatment. R3: In a sub-population of IR patients with high risk of relapse (IR-high) tests if the relapse-risk can be reduced (and thereby the disease-free survival increased) by the randomised introduction of either two cycles a new agent (Inotuzumab) before the Maintenance phase or the introduction of low-dose 6-Thioguanin (6TG) into the Maintenance phase (TEAM) with monitoring of 6TG-incorporation into the DNA of leukocytes. |
| Control (C) | R1: standard of care (delayed Intensification phase of treatment contains Doxorubicin) R2: standard of care (Delayed Intensification phase contains Doxorubicin and maintenance phase contains Vincristine(VCR)/ Dexamethasone(Dexa) pulses) R3: standard of care |
| Outcome (O) | R1: This is a non-inferiority comparison where we aim to show that removing anthracyclines does not result in an unacceptable reduction in the DFS rate. R2: This is a non-inferiority comparison where we aim to show the removal of anthracyclines in DI OR vincristine and dexamethasone in maintenance do not result in an unacceptable reduction in the DFS rate. R3: The primary endpoint is DFS, where we aim to show an improvement in the 5-year rate from 84% to 90% (i.e. an HR of 0.61). |
| Trial Design | Backbone protocol with 3 randomised questions |
| Sample Size | R1: Over a period of 8 years we expect to be able to recruit 932 patients to this randomisation (1:1) Belgian participation 510 patients included |
| Trial duration | 192 months from FPI to CSR |
| € 2,920,000 |
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Sponsor |
International sponsor: Karolinska University Hospital Belgian Coordinating Centre: UZ GENT |
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Chief Investigator |
Sponsor: MD PhD Mats Heyman, Karolinska Institut, Sweden BCC: Dr Veerle Mondelaers, Ghent University Hospital, Belgium |
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Trial Coordinator/PM |
Marlies Bekaert, HIRUZ, Ghent University Hospital, Belgium |
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External Partners |
Belgian Society for Pediatric Hematology and Oncology (BSPHO) |
|
Sites |
Departments of pediatric hemato-oncology of 8 different university hospitals across Belgium |
Clinicaltrials.gov: NCT04307576
EU CT number: 2022-501050-11-01
Investigator-led workstream 2017
