KCE-17010: A trial for children and young adults with acute lymphoblastic leukaemia (ALL) - ALLTogether1

Summary (French or Dutch)

Acute lymphoblastic leukemia (ALL) is the most frequent cancer in children 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 with ALL have greatly improved, with a survival rate of more than 85-90%. Nevertheless, for some children the treatment will remain not efficient enough. While other children (40-50%) risk overtreatment resulting in unnecessary, sometimes serious side effects. Under-and overtreatment can only be prevented if which children need which treatment and its effectiveness can be determined early during the treatment leading to an adjustment of therapy for every 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 the low risk patients on the one hand, and an intensification of treatment for the patients with the greatest risk of relapse by addition of innovative therapy (inotuzumab) or combination therapy (TEAM) on the other hand. The scope of this study is to create a framework in Belgium for rolling out and harmonising this European treatment plan for best standard of care aiming to improving the survival and quality of survival for children with ALL in Belgium.

Trial Description
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 acute lymphoblastic leukemia

Intervention (I)

R1: In low risk (VLR) 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 7 years we expect to be able to recruit 1413 patients to this randomisation (1:1)

R2: Over a period of 7 years we expect to be able to recruit 1530 patients to this randomisation (1:1:1)

R3: With 1228 patients recruited over 5 years (assuming 39% are Intermediate Risk-High and 80% accept randomisation), an additional 2 years follow-up, a 2-sided 5% alpha we will have 84% power to detect this difference.

Belgian participation 510 patients randomised

Other participating countries: Sweden, Denmark, Norway, Finland, Iceland, Lithuania, Estonia, UK, Netherlands, Germany, Portugal, Ireland and France.

Trial duration

150 months

Budget

3.3 Million Euro (incl. VAT)

Of which approx. 2.6 Million Euro incl. VAT is BCC and sites costs and 700,000 Euro incl. VAT is diagnostic lab tests.

Status

Open

 

Trial team

Sponsor

International sponsor: Karolinska University Hospital

Belgian Coordinating Centre: UZ GENT

Chief Investigator

Sponsor: MD PhD Mats Heyman, Karolinska Institut, Sweden

BCC: Dr Veerle Mondelaers, Ghent University Hospital, Belgium

Trial Coordinator/PM

Marlies Bekaert, HIRUZ, Ghent University Hospital, Belgium

External Partners

Belgian Society for Pediatric Hematology and Oncology (BSPHO)

Sites

Departments of pediatric hemato-oncology of 8 different university hospitals across Belgium
Documents
Protocol:  
Report: Q3/2029

 

Publication

 

References

Clinicaltrials.gov: NCT04307576

Eudract number: 2018-001795-38

Funding scheme

Investigator-led workstream 2017