Acute lymphoblastic leukaemia (ALL) MedDRA version: 21.0 Level: LLT Classification code 10000844 Term: Acute lymphoblastic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Karolinska University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients newly diagnosed with T-lymphoblastic (T-cell) or B-lymphoblastic precursor (BCP) leukaemia (ALL) according to the WHO-classification of Tumours of Haematopetic and Lymphoid Tissues (Revised 4th edition 2017) and with a diagnosis confirmed by an accredited laboratory at a participating paediatric oncology or adult haematology centre. 2. Age = 0 days and =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Age 45 years at diagnosis (from the 46th birthday onwards) 3. Patients with a previous malignant diagnosis (ALL as a second malignant neoplasm - SMN). 4. Relapse of ALL. 5. Patients with mature B-ALL (as defined by surface IG positivity) or any patients with IG::MYC and a concurrent BCL2/6 rearrangement. 6. Patients with Ph-positive ALL (documented presence of t(9;22)(q34;q11) and/or of the BCR::ABL1 fusion transcript). These patients will be transferred to an adequate trial for t(9;22) if available. 7. Previously known ALL prone syndromes (e.g. Li-Fraumeni syndrome, germline ETV6 mutation), except for Down syndrome. Exploration for such ALL prone syndromes is not mandatory and patients in whom genetic work-up reveals a new germ-line mutation (index-cases) will remain in the study. 8. Treatment with systemic corticosteroids (>10mg/m2/day) for more than one week and/or other chemotherapeutic agents in a 4-week interval prior to diagnosis (pre-treatment). 9. Pre-existing contraindications to any treatment according to the ALLTogether protocol (constitutional or acquired disease prior to the diagnosis of ALL preventing adequate treatment). 10. Any other disease or condition, as determined by the investigator, which could interfere with the participation in the study according to the study protocol, or with the ability of the patients to cooperate and comply with the study procedures. 11. Women of childbearing potential who are pregnant at the time of diagnosis. 12. Women of childbearing potential and fertile men who are sexually active and are unwilling to use adequate contraception during therapy. Efficient birth control is required, see section 17.8. 13. Female patients, who are breast-feeding. 14. Essential data missing from the registration of characteristics at diagnosis (in consultation with the protocol chair). For each intervention/randomisation an additional set of exclusion-criteria is provided.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of ALLTogether is to improve survival and quality of survival in infants, children and young adults with acute lymphoblastic leukaemia by a number of interventions that will be tested in a randomised fashion, compared with well-defined control-populations within the Protocol or explored in a non-randomised fashion either to obtain baseline information regarding characteristics, leukaemia-specific outcomes and toxicity or to be compared with well defined historical controls. A sub-group of patients will be identified that may benefit from novel immunotherapy.;Secondary Objective: •To investigate if SR-& IR-low patients can benefit from de-intensification of therapy. Overall survival(OS) and leukaemia outcomes are balanced against toxicity including relapse treatment. Quality of life(QoL) measurements will ascertain and compare the burden of therapy •To ascertain if addition of Inotuzumab(InO) or low-dose 6-thioguanine (TEAM) impacts OS or other adverse outcomes and to assess if the toxicity induced by InO/TEAM is significant & acceptable. QoL measurements will assess the burden of the experimental intensifications •For patients treated with TKI, baseline data regarding OS, adverse outcomes, toxicity and QoL will be collected for future reference •To ascertain if replacing conventional chemotherapy with blinatumomab can improve leukaemic outcomes and reduce toxicity in Down patients •For patients defined as eligible for CAR-T survival, specific leukaemic adverse events, toxicity & QoL resulting from conventional HR-therapy & CAR-T cell treatment is measured;Primary end point(s): - The primary endpoint for the whole protocol (compared with the legacy protocols of the participating study-groups forming the consortium) is event-free survival (EFS) – as defined in the protocol. - The primary endpoint for the randomised interventions is disease-free survival (DFS) – as defined in the protocol. - The primary endpoint for the replaceme | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Main study secondary end-points The most important secondary outcome is overall survival (OS). Additional secondary measures of antileukaemic efficacy are: rate of -death during induction, -resistant disease, cumulative incidence of: -relapse (ciR), -death in first complete remission (ciDCR1) and -second malignancy (ciSMN). Over- and under-treatment events will also be combined into resulting treatment-related mortality (TRM) and leukaemia specific mortality (LSM) rates. Since over-treatment also includes cured patients who suffer potentially permanent side-effects, data will be collected regarding the incidence of some adverse events of special interest. De-escalation of therapy may also result in relapses that have to be rescued with allogeneic stem-cell transplant (allo-SCT), which is associated with serious permanent side effects. Therefore, the incidence of allo-HSCT in CR1 and CR2 will also be measured. An important aspect of evaluation of the quality of survival is measurement of quality of life (QoL). The whole protocol, as well as each of the non-randomised and randomised interventions will also be evaluated by measurements of quality of life (QoL). QoL will be measured by EQ5D-based instruments before and after all the randomised phases in all randomisations as well as later in the therapy and after cessation of treatment. R1 and R2 secondary end-points Efficacy: • Overall survival (OS) • Cumulative incidence of relapse (ciR) • Cumulative incidence of Death in CR1 (ciDCR1) • Cumulative incidence of SMN (ciSMN) • Fraction of surviving patients treated with allogeneic stem-cell transplant in second remission • Cumulative incidence of HSCT in CR2 Toxicity: The studies are powered to answer the primary end-point non-inferiority question with a certain safety-margin. Even if reduction of exposure to potentially toxic therapy is an objective in itself, it is also reasonable to show some immediately measurable benefit from the re | — |
Countries
Belgium, Denmark, Estonia, Finland, France, Germany, Iceland, Ireland, Lithuania, Netherlands, Norway, Portugal, Réunion, Sweden, United Kingdom
Contacts
Public ContactKarin Flood
Karolinska Institutet
Outcome results
None listed