acute lymphoblastic leukemia blood cancer
Conditions
Interventions
- R1: omission of Doxorubicin in the delayed intensification phase of the SR
treatment
- R2: omission of Doxorubicin in the delayed intensification phase or
Vincristine-Dexamethasone pulses in maint
collection of additional bonemarrow and blood at standard
sampling timepoints
- Replacement of 2 consolidation cycles with 2 cycles of Blinatumomab in IR/HR
patients with Down Syndrome
- Quality of
Sponsors
Karolinska University Hospital
Eligibility
Age
No minimum to 64 Years
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
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 documented presence of one of the t(8;14)(q24;q32), t(2;8)(p12;q24), t(8;22)(q24;q11) translocations involving the MYC gene and breakpoint as in mature B-NHL/ALL) 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 germline 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 17.7. 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 |
|---|---|
| - 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 DS study is fraction of MRD undetectable patients (*Complete MRD response*) at the end of one cycle of Blinatumomab | — |
Secondary
| Measure | Time frame |
|---|---|
| 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) • The components of the primary end-point - DFS (ciR, ciDCR1 and ciSMN) are relevant secondary end-points since they are likely to work in opposite directions in a de-escalation setting • Fraction of surviving patients treated with allogeneic stem-cell transplant in second remission and cumulative incidence of HSCT in CR2 will also be measured 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 | — |
Countries
Netherlands
Outcome results
None listed