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RecruitingNCT04307576Updated Aug 12, 2026

A Treatment Study Protocol for Participants 0-45 Years With Acute Lymphoblastic Leukaemia

A Phase 3 interventional study of Omitted Doxorubicin and Omitted Vincristine+Dexamethasone pulses in Leukemia, Acute Lymphoblastic, sponsored by Mats Heyman. Recruiting at 137 sites in 15 countries. Open to participants aged 0 Years to 45 Years. Per ClinicalTrials.gov, last updated 2026-08-12.

Sponsored by Mats Heyman · Phase 3, Interventional, and Treatment

From the registry’s dates

  • Started Jul 2020; still recruiting 6 years 3 months later.
Phase
Phase 3
Study type
Interventional
Enrollment
6,430
Allocation
Randomized
Ages
0 Years to 45 Years
Sex
All
01

Study summary

ALLTogether collects the experience of previously successful treatment of infants, children and young adults, with ALL from a number of well-renowned study groups into a new master protocol, which is both a comprehensive system for stratification and treatment of ALL in this age-group as well as the basis for several randomised and interventional trials included in the study-design.

Read the detailed description

ALLTogether is a European clinical treatment study for acute lymphoblastic leukaemia (ALL) in infants, children and young adults. The aims are to improve survival and quality of survival. In young people, ALL has excellent outcome with an overall survival of about 92% in children and 75% in young adults. Infants with BCP-ALL and KMT2A-rearrangements have a worse outcome and are treated according to separate protocols, but infants with KMT2A-germline and T-cell ALL have acceptable outcome on standard ALL therapy. However, patients still die of disease - from relapse because of under-treatment and a large fraction of patients are also over-treated: All patients risk treatment-related death and some suffer long-term side-effects or secondary cancer. To show improvement with such good survival, large populations are needed.

Study groups from Sweden, Norway, Iceland, Denmark, Finland, Estonia and Lithuania (NOPHO), the UK (UKALL), the Netherlands (DCOG), Germany (COALL), Belgium (BSPHO), Portugal (SHOP), Ireland (PHOAI), and France (SFCE), have designed a common treatment protocol.

The study has a complex clinical trial design with sub-protocols (the randomisations / intervention) connected to a master protocol. The master protocol consists of well established therapy-elements and in its design typical for current ALL therapy. The master protocol therapy is in the study design considered as standard of care (SOC) therapy for infants, children and young adults with ALL.

The study structure is defined by a master protocol onto which randomised and interventional sub-protocols as well as sub-studies may be added, run and stop in a modular fashion.

The randomisations / intervention may identify therapy that is less toxic, but equally efficacious for sub-groups of patients and innovative therapy that may reduce relapses and death from ALL. In the master protocol, improved risk-stratification is likely to increase survival and reduce unnecessary toxicity and the introduction of therapeutic drug monitoring (TDM) of Asparaginase activity will make the use of Asparaginase more rational and efficient and may thus improve overall outcomes.

The investigators hypothesise that patients stratified to the standard-risk group are over-treated. Therefore, it will be tested if the treatment can be safely reduced. In the R1 randomisation, patients will be randomised to receiving the Delayed Intensification (DI) phase of therapy with or without the anthracycline Doxorubicin.

A similar hypothesis of over-treatment will also be tested in patients stratified to the intermediate risk-low group. In the R2 randomisation patients will be randomly assigned to either removal of Doxorubicin during the DI phase or removal of Vincristine and Dexamethasone pulses during the maintenance phase or to the control group, which will be treated with Doxorubicin in DI as well as Vincristine and Dexamethasone pulses during maintenance. Patients will only be randomised once.

Randomisation R1 and R2 are only considered for children since adults have worse outcome and very poor survival after relapse, but the risk-stratification is likely to reduce the number of high-risk cases also in the adult-group.

Patients stratified as intermediate risk-high (IR-high) are identified as having an increased risk of relapse and thus a less favourable prognosis than the standard- and intermediate risk-low groups, but a more favourable prognosis than the high risk patients. The majority of all relapses in childhood ALL is expected to occur in the IR-high group. Following a relapse, only approximately 40% of the children can be successfully treated again and for adults the corresponding figure is less than 20 %, so preventing relapses is very important. New treatment options that improves the antileukaemic efficacy and which have an improved safety profile are urgently needed.

For IR-high patients Randomisation 3 (R3) is available. In R3 patients will be randomised to receive either:

  1. the first six weeks of maintenance treatment are replaced by two 3- week cycles of Inotuzumab ozogamicin (InO) - Besponsa®. This is followed by maintenance therapy similar to the standard arm.
  2. the addition of low dose 6-tioguanine (6TG) as an addition to the standard maintenance therapy.
  3. standard maintenance therapy.

Patients with ABL-class fusions in their leukaemic clone will, as a non-randomised experimental intervention, be treated with an addition of a tyrosine-kinase inhibitor during the induction phase (for patients \<25 years) and from the consolidation phase (patients ≥25 years). This intervention may shift therapy for previously resistant cases to lower intensity treatment with the associated reduced morbidity and may also reduce the number of relapses in analogy with the results in Ph+ ALL. The reason for not performing a randomised comparison is the rarity of the aberration and also the diversity of ABL-class fusions, reducing statistical power for any comparison further. For this reason, the results of this intervention may be pooled with other study-groups trying similar approaches.

A new intervention is introduced for Down syndrome patients with CD19 positive ALL: ALLTogether1 DS (NRI2). For Down syndrome-ALL patients who have end of Induction MRD detectable but \<25% two conventional chemotherapy consolidation blocks will be replaced with two blocks of Blinatumomab. Recruitment to this intervention was closed at the end of August 2024.

For high-risk B-lineage patients, CAR-T therapy can be an alternative to high-risk blocks and stem-cell transplant, but in this case the intervention (CAR-T infusion) will be performed outside the ALLTogether1 study. However, the stratification-system in ALLTogether1 will define the population with a potential CAR-T indication.

ALLTogether1 also includes five sub-studies:

Efficacy and pharmacokinetics of Imatinib in ABL-class fusion positive ALL

Target population: All ABL-class patients enrolled in the ALLTogether study. Biomaterials to be collected at diagnosis, during TKI treatment, follow-up and relapse.

Aims

  1. To determine the efficacy and dosing target of imatinib in the treatment of ABL-class leukemia
  2. To find the best discriminative biomarkers for TKI response in ABL-class ALL
  3. To determine the frequency of intrinsic (at diagnosis) and acquired TKI resistance (due to treatment), including backtracking of mutations using imatinib PK/PD findings during treatment
  4. To find causes of TKI resistance in ABL-class patients
  5. To describe the pharmacokinetics of Imatinib in TKI-treated patients

Objectives

  1. To determine the percent of ABL-class patients who need to switch from IR-high to HR because of high MRD levels
  2. To determine the effect of imatinib exposure on clinical outcome, including pharmacokinetic measurements of imatinib
  3. To determine the molecular response to imatinib by monitoring fusion gene levels and mutational spectrum at diagnosis and during follow up
  4. To determine whether the molecular response parameters reflect the Ig/TCR MRD or flow-MRD response or are a better predictor of therapy failure than Ig/TCR or flow-based MRD monitoring
  5. To determine the phosphorylation status of ABL-class proteins and presence of TKI-resistance associated mutations in ABL genes prior to imatinib treatment and the emergence of such mutations during treatment with imatinib
  6. To determine the presence of mutations in regulatory /other genes before and during imatinib treatment and functionally address the importance of these mutations in TKI resistance
  7. To determine whether the efficacy of TKIs depends on the type of fusion gene
  8. To describe inter- and intraindividual variations in imatinib PK (=trough levels) during therapy of ABL-class ALL
  9. To describe associations between PK of imatinib and end-of-induction MRD (\<25 yrs only) and end-of-consolidation MRD (all patients)
  10. To describe associations between imatinib PK and relapse rates (overall, bone-marrow and CNS), event-free survival as well as overall survival;
  11. To describe associations between imatinib PK and toxicities (including e.g. height z-scores at diagnosis and end of therapy, pancreatitis, treatment delays) with focus on those toxicities that are routinely monitored in ALLTogether.

Biomarkers to Reform Approaches to therapy-Induced Neurotoxicity (BRAIN)

Target population: All patients registered on ALLTogether1 aged ≥ 4 years at end of therapy (Arm A) and all patients registered on ALLTogether1 aged 2-21 years at start of therapy (Arm B) and without:

  1. Pre-existing neurodevelopmental delay (e.g Trisomy 21) prior to diagnosis of ALL
  2. Significant visual or motor impairment preventing use of a computer/touch screen ipad

All centres are invited to enrol to arm A (Main BRAIN) of the study. Arm B (Longitudinal BRAIN) will be carried out in selected centres.

Aims

  1. To implement universal screening of all children for adverse neurocognitive outcomes at the end of treatment using a validated user-friendly computer software programme (CogState) and compare neurocognitive outcomes by treatment allocation (Arm A).
  2. To identify risk factors for adverse outcomes including whether acute neurotoxic events are associated with poor performance on cognitive tests at end of therapy compared to patients without acute neurotoxicity (Arm A).
  3. To examine changes in neurocognitive performance over time and the risk/protective factors associated with differences in outcome, such as demographic, clinical, and physical/psychosocial factors (Arm B).

Primary end-point

a. Proportion of children with a z-score \<1.5 on detection and/or identification CogState tasks in each treatment arm at the end of ALL therapy. A z-score \< 1.5 correlates with moderate cognitive impairment at a level that may require additional support.

Secondary and exploratory end-points

  1. Association between CogState scores at end of treatment and overt neurotoxic episodes as recorded on the trial adverse event database.
  2. Association between Cogstate scores and clinical and demographic variables - age, sex, ethnicity, CNS status.
  3. Proportion of children with scores \<1.5SD for one card learning (learning), one back (working memory), Groton's maze (executive function), digit symbol substitution (processing speed) on different treatment arms.
  4. Association between CogState scores and patient reported outcome measures/Quality of life measurements collected as part of the main ALLTogether1 trial.
  5. Changes in neurocognitive scores over time, including CogState and BRIEF-2/BRIEF-A scores.
  6. Association between neurocognitive scores over time and interactions with demographic variables (age, sex), clinical variables (treatment arm, neurotoxicity), social-emotional and physical functioning (SDQ, PedsQL 4.0 Generic; PedsQL 3.0 Fatigue), and family factors (MEES; PedsQL FIM).

Association between asparaginase activity levels and outcome

Target population: All patients included in the ALLTogether1 protocol are eligible for participation.

Primary aim

To study the association between asparaginase activity levels and outcome (MRD, relapse, survival)

Secondary aims

  1. To evaluate the association between asparaginase activity levels and toxicities, such as pancreatitis, infections and deep venous thrombosis (DVT)
  2. To evaluate the association between asparaginase activity levels and hepatotoxicity in a subset of patients

CSF-Flow

Target population: All patients included in the ALLTogether1 protocol are eligible for participation

Aims

  1. To use cerebrospinal fluid (CSF) flow cytometry (FCM) to improve the accuracy of diagnostic tests for CNS leukaemia compared to conventional CSF cytology. An associated objective will be to develop a recommended protocol for CSF flow cytometry with external quality assessment to ensure uniformity of measurement across the ALLTogether consortium.
  2. To investigate whether negative FCM identifies a group of children at very low risk of CNS relapse, suitable for testing de-escalation of CNS-directed therapy in future trials.
  3. To investigate whether positive FCM can identify children at increased risk of CNS relapse and whether patients with persistent positivity (FCM positive at day 15 onwards) might benefit from studies testing escalated CNS-directed therapy or a switch to more intensive treatment arms.
  4. To collect matching CSF supernatant for studies comparing CSF FCM with soluble biomarkers (e.g. metabolic, cell-free DNA, proteomic and microRNA).

Maintenance therapy pharmacokinetics/-dynamics study

Target population: All patients included in the ALLTogether1 protocol are eligible for participation. For IR-high patients participating in the randomised InO- and TEAM sub-protocols, the monitoring of 6-mercaptopurine (6MP)/Methotrexate (MTX) metabolites at three months intervals is mandatory.

Aims and specific objectives

  1. To map pharmacokinetics of 6MP and MTX during maintenance therapy in all patients in the ALLTogether protocol.
  2. To associate metabolite profiles with TPMT and NUDT15 variants, as routinely analysed in ALLTogether.
  3. To explore the association of event-free survival with DNA-TG and other 6MP/MTX metabolites.
  4. To explore the association between risk of second cancers with DNA-TG and other 6MP/MTX metabolites.
  5. To explore the association of risk of invasive infections with DNA-TG and other 6MP/MTX metabolites.
  6. To explore the association of risk of osteonecrosis with DNA-TG and other 6MP/MTX metabolites.
  7. To explore the association of sinusoidal obstruction syndrome with DNA-TG and other 6MP/MTX metabolites.
02

Conditions studied

  • Leukemia, Acute Lymphoblastic

Keywords

  • Leukemia
  • Acute Leukemia
  • ALL
  • ALLTogether
  • Leukaemia
  • Inotuzumab ozogamicin
  • Besponsa
  • ALLTogether1
  • Blinatumomab
  • Blincyto
  • 6-tioguanine
  • 6-thioguanine
03

In context

Precursor Cell Lymphoblastic Leukemia-Lymphoma

2,584 studies on the registry are indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma; 473 are open to participants now.

This study's planned enrollment of 6,430 is above the median of 40 across 1,952 interventional studies indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma.

Browse Precursor Cell Lymphoblastic Leukemia-Lymphoma studies →

Lead sponsor

Mats Heyman is the lead sponsor of 2 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
0 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Patients newly diagnosed with T-lymphoblastic (T-cell) or B-lymphoblastic precursor (BCP) leukaemia (ALL) according to the WHO-classification of Tumours of Haematopoetic 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.
  • Age 0 - \< 46 years (one day before 46th birthday) at the time of diagnosis with the exception of infants with KMT2A-rearranged (KMT2A-r) BCP ALL.
  • Patients with surface immunoglobulin negative (sIG-) BCP-ALL and an IG::MYC rearrangement, unless they have a concurrent BCL2/6 rearrangement. T-ALL patients with MYC translocations.
  • signed by the patient and/or parents/legal guardians according to country-specific age-related guidelines.
  • The ALL diagnosis should be confirmed by an accredited laboratory at a participating paediatric oncology or adult haematology centre.
  • The patient should be diagnosed and treated at a participating paediatric oncology or adult haematology centre in the participating countries.
  • The patient should be a resident in one of the participating countries on a permanent basis or should intend to settle in a participating country, for instance by an application for asylum. Patients who are visiting the country as tourists should not be included. However, returning expatriots with primary diagnosis abroad may be included if no treatment has been administered and the diagnostic procedures are repeated at a participating centre.
  • All women of (WOCBP) have to have a negative pregnancy test within 2 weeks prior to the start of treatment.
  • For each intervention/randomisation an additional set of inclusion-criteria is provided.

Exclusion criteria

Exclusion Criteria:

  • Age \< 365 days and KMT2A-rearranged (KMT2A-r) BCP-ALL (documented presence of a KMT2A-split by FISH and/or a KMT2A fusion transcript).
  • Age >45 years at diagnosis.
  • Patients with a previous malignant diagnosis (ALL as a second malignant neoplasm - SMN).
  • Relapse of ALL.
  • Patients with mature B-ALL (as defined by surface IG positivity) or any patients with IG::MYC and a concurrent BCL2/6 rearrangement.
  • Patients with Ph-positive ALL (documented presence of t(9;22)(q34;q11) and/or of the BCR::ABL fusion transcript). These patients will be transferred to an appropriate trial for t(9;22) if available.
  • 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.
  • Treatment with systemic corresponding to (>10mg prednisolone/m2/day) for more than one week and/or other chemotherapeutic agents in a 4-week interval prior to diagnosis (pre-treatment).
  • Pre-existing to any treatment according to the ALLTogether protocol (constitutional or acquired disease prior to the diagnosis of ALL preventing adequate treatment).
  • 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.
  • Women of who are pregnant at the time of diagnosis.
  • Women of childbearing potential and fertile men who are sexually active and are unwilling to use adequate during therapy. Efficient birth control is required.
  • Female patients, who are breast-feeding.
  • 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.
Terms in these criteria, in plain language(5)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
6,430 participants (estimated)

Study arms

  • No intervention
    R1 - SR standard arm

    Standard risk arm receiving standard treatment (Delayed Intensification including Doxorubicin).

  • Experimental
    R1 - SR experimental arm

    Standard risk arm, receiving Delayed Intensification without Doxorubicin IV 3 x 30 mg/m2/dose.

    Drug: Omitted Doxorubicin

  • No intervention
    R2 - IR-low standard arm

    Standard treatment with Delayed Intensification including Doxorubicin and Maintenance including Vincristine+Dexamethasone pulses.

  • Experimental
    R2 - IR-low experimental arm A

    Standard treatment with omission of Doxorubicin IV 3 x 30 mg/m2/dose in the Delayed Intensification phase.

    Drug: Omitted Doxorubicin

  • No intervention
    R3 - IR-high standard arm

    Intermediate risk high arm receiving Standard Maintenance Therapy.

  • Experimental
    R3-InO - IR-high experimental arm

    Inotuzumab IV 0,5 mg/m2, given on days 253, 260, 267 and on days 274, 281, 288 before start of Standard Maintenance Therapy.

    Drug: Inotuzumab Ozogamicin+Standard Maintenance Therapy

  • Experimental
    ABL-class fusions intervention

    Imatinib p.o. 340 mg/m2 given daily from day 15 or 30 (depending on age) to the end of therapy (week 106) in addition to Standard IR-high chemotherapy.

    Drug: Imatinib

  • Experimental
    R3-TEAM - IR-high experimental arm

    6-tioguanine p.o, 2,5-12,5 mg/m2, given daily in addition to Standard Maintenance Therapy.

    Drug: 6-tioguanine+Standard Maintenance Therapy

  • Experimental
    ALLTogether1 DS Blinatumomab intervention

    Blinatumomab IV, 5 mcg/m2/day up to 28 mcg/day (detailed dosing in protocol) continous infusion. Two 28 day courses with a two week treatment free interval in between. Blinatumomab courses replace Consolidation 1 and Consolidation 2 in the standard protocol adapted for Down syndrome patients.

    Drug: Blinatumomab

  • Experimental
    R2 - IR-low experimental arm B

    Standard treatment with omission of monthly pulses of Vincristine IV 1,5 mg/m2/dose and 5 days of Dexamethasone p.o. 6 mg/m2/day in the Maintenance Phase.

    Drug: Omitted Vincristine+Dexamethasone pulses

Interventions

  • DrugOmitted Doxorubicin

    Omission of IV Doxorubicin

  • DrugOmitted Vincristine+Dexamethasone pulses

    Omission of Vincristine+Dexamethasone pulses

  • DrugInotuzumab Ozogamicin+Standard Maintenance Therapy

    Addition of IV Inotuzumab ozogamicin before Maintenance Therapy

    Also known as: Besponsa+Maintenance Therapy

  • DrugImatinib

    p.o. Imatinib

  • Drug6-tioguanine+Standard Maintenance Therapy

    Addition of p.o. 6-tioguanine to Standard Maintenance Therapy

  • DrugBlinatumomab

    IV Blinatumomab

    Also known as: Blincyto

06

What researchers measure

Primary outcomes

  1. Event-free survival (EFS) for the whole protocol

    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.

    Time frame: 5 year estimates from the time of diagnosis will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  2. Event-free survival (EFS) for the TKI intervention

    The primary endpoint for the TKI intervention is event-free survival (EFS) - as defined in the protocol, from the start of TKI until event or end of follow-up

    Time frame: From the start of TKI (day 15 or day 30), 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up for all interventions except Inotuzumab-randomisation (minimum 2-year follow-up).

  3. Disease-free survival (DFS) R1 + R2

    The primary endpoint for Randomisation 1 and 2 is disease-free survival (DFS) - as defined in the protocol counting from the time of randomisation

    Time frame: 5 and 8 year estimates from the time of randomisation will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  4. Disease-free survival (DFS) R3

    The primary endpoint for Randomisation 3 and the ABL-class fusion intervention is disease-free survival (DFS) - as defined in the protocol counting from the time of randomisation (R3) and the start of TKI-therapy (ABL-class fusion intervention).

    Time frame: 5 year estimates from the time of randomisation will be measured but adequate follow-up for these estimates will be ensured: at least 2-year follow-up

  5. MRD response after 1 cycle of Blinatumomab

    Fraction of patients with undetectable MRD ("Complete MRD response") at the end of one cycle of Blinatumomab (+/- 1 week)

    Time frame: End of first Blinatumomab infusion +/- 1 week

Secondary outcomes

  1. Overall survival (OS) for the whole protocol

    Overall survival defined as time from diagnosis to death or end of follow-up for surviving patients.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  2. Overall survival (OS) for R1 + R2

    Overall survival defined as time from randomisation to death or end of follow-up for surviving patients.

    Time frame: 5 and 8 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  3. Overall survival (OS) for R3

    Overall survival defined as time from randomisation to death or end of follow-up for surviving patients.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up

  4. Overall survival (OS) for R3-TEAM associated with DNA-TG

    Overall survival as defined above in relation to DNA-TG.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up

  5. Overall survival (OS) for TKI

    Overall survival defined as time from start of TKI to death or end of follow-up for surviving patients

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up (TKI).

  6. Overall survival (OS) for ALLTogether1 DS

    Overall survival defined as time from start of Blinatumomab to death or end of follow-up for surviving patients

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  7. Induction death

    Fraction of patients who die as well as cumulative incidence of death before achieved complete remission (CR) within the time-frame described in the protocol

    Time frame: From diagnosis until death before remission (at the earliest, day 29) or in case of no CR day 29, completion of induction and consolidation 1 (protocol day 99 - Down) and in addition 3 high-risk blocks (protocol day 134 - all other patients)

  8. Resistant disease

    Fraction of patients as well as cumulative incidence of resistant disease as described in the protocol. Induction death as competing risk.

    Time frame: From diagnosis until achieved complete remission (at the earliest, day 29) or in case of no CR day 29, assessment after induction and consolidation 1 (protocol day 99-Down patients) and in addition 3 high-risk blocks (protocol day 134-all other patients)

  9. Cumulative incidence of relapse for the whole protocol

    Time from achieved complete remission until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  10. Cumulative incidence of relapse for R1 + R2

    Time from randomisation until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.

    Time frame: 5 and 8 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  11. Cumulative incidence relapse for R3

    Time from randomisation until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up

  12. Cumulative incidence relapse for R3-TEAM in association with DNA-TG

    Cumulative incidence of relapse as defined for R3 in association with DNA-TG for R3-TEAM. Second malignancy, death in complete remission as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up

  13. Cumulative incidence CD22 negative relapse for R3

    Time from randomisation until relapse without expression of CD22 as defined in the protocol or end of follow-up. Second malignancy, death in complete remission and relapse with CD22 expression as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up

  14. Cumulative incidence relapse for TKI

    Time from start of TKI until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up

  15. Cumulative incidence relapse for ALLTogether1 DS

    Time from start of Blinatumomab until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up

  16. Cumulative incidence of CD19 negative relapse for ALLTogether1 DS

    Time from start of Blinatumomab until CD19 negative relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission and CD19 positive relapse as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up

  17. Cumulative incidence of second malignant neoplasm (SMN) for the whole protocol

    Time from achieved complete remission until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  18. Cumulative incidence of second malignancy for R1+R2

    Time from randomisation until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.

    Time frame: 5 and 8 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  19. Cumulative incidence of second malignancy for R3

    Time from randomisation until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up.

  20. Cumulative incidence of second malignancy for R3-TEAM in association with DNA-TG

    Cumulative incidence of second malignancy as defined above for R3 in association with DNA-TG for R3-TEAM. Relapse and death in complete remission as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up.

  21. Cumulative incidence of second malignancy for TKI

    Time from start of TKI until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  22. Cumulative incidence of second malignancy for ALLTogether1 DS

    Time from start of Blinatumomab until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  23. Cumulative incidence of death in complete remission for the whole protocol

    Time from achieved complete remission until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  24. Cumulative incidence of death in complete remission for R1+R2

    Time from randomisation until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.

    Time frame: 5 and 8 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up.

  25. Cumulative incidence of death in complete remission for R3

    Time from randomisation until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up

  26. Cumulative incidence of death in complete remission for TKI

    Time from start of TKI until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up

  27. Cumulative incidence of death in complete remission for ALLTogether1 DS

    Time from start of Blinatumomab until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up

  28. Cumulative incidence of treatment-related mortality for the whole protocol

    Time from diagnosis until death during induction, death in complete remission or death from second malignant neoplasm (if not related to SMN-treatment).

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  29. Cumulative incidence of treatment-related mortality R1+R2

    Time from randomisation until death in complete remission or death from second malignant neoplasm (if not related to SMN-treatment).

    Time frame: 5 and 8 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up.

  30. Cumulative incidence of treatment-related mortality R3

    Time from randomisation until death in complete remission or death from second malignant neoplasm (if not related to SMN-treatment).

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up

  31. Cumulative incidence of treatment-related mortality TKI

    Time from start of TKI until death in complete remission or death from second malignant neoplasm (if not related to SMN-treatment).

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up

  32. Leukaemia specific mortality for the whole protocol

    Time from diagnosis until death after resistant disease or relapse - as defined in the protocol.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  33. Leukaemia specific mortality for R1+R2

    Time from randomisation until death after relapse - as defined in the protocol.

    Time frame: 5 and 8 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.

  34. Leukaemia specific mortality for R3

    Time from randomisation until death after relapse - as defined in the protocol.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up

  35. Leukaemia specific mortality for TKI

    Time from start of TKI until death after relapse - as defined in the protocol.

    Time frame: 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up

  36. Incidence of Adverse Events of Special Interest (AESIs) per treatment-phase in the whole protocol and TKI intervention

    Cumulative incidence of 19 AESIs as defined in the protocol

    Time frame: From time of diagnosis after each treatment-phase (one extra in the middle of maintenance) and annually until 5 years from discontinuation of therapy.

  37. Incidence of Adverse Events of Special Interest (AESIs) extra assessment (R1+R2)

    Cumulative incidence of 4 additional AESIs as defined in the protocol

    Time frame: Cumulative incidence of AESIs estimated 3 months after start of maintenance (R1+R2) and at the end of maintenance (R2)

  38. Incidence of Adverse Events of Special Interest (AESIs) extra assessment (R3)

    Cumulative incidence of 3 additional AESIs as defined in the protocol

    Time frame: Cumulative incidence of AESIs estimated at the end of maintenance.

  39. Incidence of Serious Adverse Events (SAEs) and Adverse Events (AEs) related to R3

    Cumulative incidence of SAEs and AEs (with limitations) as defined in the protocol

    Time frame: From time of randomisation until the end of maintenance therapy (approximately 77 weeks from randomisation)

  40. Quantitative measures of toxicity R1+R2

    Days: in hospital, with iv antibiotics, with iv analgesics, with iv nutritional support

    Time frame: From time of randomisation, assessment after delayed intensification and 6 weeks after start of maintenance

  41. Metabolic consequences of steroid exposure (R2)

    Measurements of BMI

    Time frame: At the end of therapy (approximately 94 weeks from randomisation) and 5 years after discontinuation of treatment

  42. Association of Disease-free survival (DFS) with DNA-TG for R3-TEAM

    Disease-free survival (DFS) - as defined above associated with DNA-TG.

    Time frame: 5 year estimates from the time of randomisation will be measured but adequate follow-up for these estimates will be ensured: at least 2-year follow-up

  43. Cumulative incidence of Sinusoidal Obstruction Syndrome (SOS) and Nodular Regenerative Hyperplasia (NRH) for R3-TEAM

    Time from randomisation until diagnosis of SOS or NRH as defined in the protocol or end of follow-up.

    Time frame: Cumulative incidence of SOS/NRH estimated at the end of follow-up.

  44. Cumulative incidence of Osteonecrosis for R3-TEAM

    Time from randomisation until diagnosis of osteonecrosis as defined in the protocol or end of follow-up.

    Time frame: Cumulative incidence of osteonecrosis estimated at the end of follow-up.

  45. Event-free survival (EFS) for ALLTogether1 DS

    Event-free survival as defined in the protocol, from the start of Blinatumomab until death from any cause, relapse, second malignancy, protocol therapy failure (MRD\>1% after 2 cycles blinatumomab and Augmented BFM consolidation) or end of follow-up.

    Time frame: From the start of Blinatumomab, 5 year estimate will be measured but adequate follow-up for this estimate will be ensured: at least 5 years follow-up.

  46. Incidence of Blinatumomab refractory disease for ALLTogether1 DS

    Incidence of progressive disease under Blinatumomab treatment or MRD ≥1% at the end of the 2nd cycle of Blinatumomab.

    Time frame: From the start of Blinatumomab until end of 2nd cycle of Blinatumomab (each cycle is 4 weeks followed by a 2-week treatment free period)

  47. Incidence of Protocol Therapy Failure for ALLTogether1 DS

    Incidence of patients who have MRD ≥1 % post 2 cycles of Blinatumomab followed by Augmented BFM consolidation, corresponding to original protocol day 99, or unchanged/increasing MRD during Augmented BFM consolidation corresponding to original protocol day 57.

    Time frame: From the start of Blinatumomab until the end of Consolidation 1 (85-140 days: 15-70 days of Blinatumomab therapy + 70 days of Consolidation 1)

Other outcomes

  1. 6-mercaptopurine and Methotrexate metabolite pharmacokinetics (i.e. Ery-TGN/MeMP/MTXpg) for R3-TEAM

    Measurements of metabolites Ery-TGN/MeMP/MTXpg during Maintenance therapy.

    Time frame: From start of Maintenance therapy until the end of Maintenance therapy (protocol week 38 until protocol week 108)

  2. Abnormal liver function parameters (including hypoglycemia) for R3-TEAM

    Liver function parameters including hypoglycemia during Maintenance therapy

    Time frame: From start of Maintenance therapy until the end of Maintenance therapy (protocol week 38 until protocol week 108)

07

Study locations

120 of 137 sites recruiting
  • L'hôpital Universitaire des enfants Reine Fabiola (Huderf)
    Brussels, 1020, Belgium
    Recruiting
    • Laurence Dedeken, M.D. · Principal investigator
  • Cliniques Universitaires Saint-Luc (UCL)
    Brussels, 1200, Belgium
    Recruiting
    • Maelle Deville, M.D. · Principal investigator
  • University Hospital Antwerp
    Edegem, 2650, Belgium
    Recruiting
    • Toon van Genechten, M.D. · Principal investigator
  • University Hospital Ghent
    Ghent, 9000, Belgium
    Recruiting
    • Veerle Mondelaers, M.D. · Principal investigator
  • University Hospital Leuven, Dept of Paediatrics
    Leuven, 3000, Belgium
    Recruiting
    • Heidi Segers, M.D. · Principal investigator
  • CHC MontLégia, Boulevard Patience et Beaujonc 2
    Liège, 4000, Belgium
    Recruiting
    • Christophe Chantrain, M.D. · Principal investigator
  • CHR de la Citadelle
    Liège, 4000, Belgium
    Recruiting
    • Marie-Françoise Dresse, M.D. · Principal investigator
  • Aalborg University Hospital, Dept of Paediatrics
    Aalborg, 9000, Denmark
    Recruiting
    • Christina Friis Jensen, M.D. · Principal investigator
  • Aarhus University Hospital
    Aarhus, 8000, Denmark
    Recruiting
    • Ingolf Mølle, M.D. · Principal investigator
  • Aarhus University Hospital, Child and Adolescent Health
    Aarhus, 8200, Denmark
    Recruiting
    • Birgitte Klug Albertsen, M.D. · Principal investigator
  • Rigshospitalet, Dept of Haematology
    Copenhagen, 2100, Denmark
    Recruiting
    • Ulrik Malthe Overgaard, M.D. · Principal investigator
  • Rigshospitalet, Dept of Paediatrics
    Copenhagen, 2100, Denmark
    Recruiting
    • Bodil Als-Nielsen, M.D. · Principal investigator
  • Odense University Hospital, Dept of Paediatrics
    Odense, 5000, Denmark
    Recruiting
    • Peder Skov Wehner, M.D. · Principal investigator
  • North Estonia Medical Centre, Dept of Haematology
    Tallinn, 13419, Estonia
    Recruiting
    • Katrin Palk, M.D. · Principal investigator
  • Tallinn Children´s Hospital, Dept of Paediatrics
    Tallinn, 13419, Estonia
    Recruiting
    • Kristi Lepik, M.D. · Principal investigator
  • Tartu University Hospital
    Tartu, 50406, Estonia
    Recruiting
    • Mari Punab, M.D. · Principal investigator
  • Helsinki University Hospital, Dept of Haematology
    Helsinki, 00029, Finland
    Recruiting
    • Ulla Wartiovaara-Kautto, M.D. · Principal investigator
  • Helsinki University Hospital, Dept of Paediatrics
    Helsinki, 00029, Finland
    Recruiting
    • Antti Kyrönlahti, M.D. · Principal investigator
  • Kuopio University Hospital, Dept of Haematology
    Kuopio, 70029, Finland
    Recruiting
    • Manna Miilunpohja, M.D. · Principal investigator
  • Kuopio University Hospital, Dept of Paediatrics
    Kuopio, 70029, Finland
    Recruiting
    • Kaisa Vepsäläinen, M.D. · Principal investigator
  • Oulu University Hospital, Dept of Haematology, Dept of Medicine
    Oulu, 90029, Finland
    Recruiting
    • Sakari Kakko, M.D. · Principal investigator
  • Oulu University Hospital, Dept of Paediatrics
    Oulu, 90029, Finland
    Recruiting
    • Riitta Niinimäki, M.D. · Principal investigator
  • Tampere University Hospital, Dept of Haematology
    Tampere, 33521, Finland
    Recruiting
    • Johanna Rimpiläinen, M.D. · Principal investigator
  • Tampere University Hospital, Dept of Paediatrics
    Tampere, 33521, Finland
    Recruiting
    • Olli Lohi, M.D. · Principal investigator
  • Turku University Hospital, Clinical Haematology and Stem Cell Transplantation Unit
    Turku, 20520, Finland
    Recruiting
    • Pia Ettala, M.D. · Principal investigator
  • Turku University Hospital, Dept of Paediatrics
    Turku, 20520, Finland
    Recruiting
    • Päivi Lähteenmäki, M.D. · Principal investigator
  • CHU Amiens Groupe Hospitalier Sud
    Amiens, 80054, France
    Recruiting
    • Camille Leglise, M.D. · Principal investigator
  • CHU Angers
    Angers, 49033, France
    Recruiting
    • Mylène Duplan, M.D. · Principal investigator
  • CHRU Besançon
    Besançon, 25030, France
    Recruiting
    • Pauline Simon, M.D. · Principal investigator
  • CHU Bordeaux - Groupe Hospitalier Pellegrin
    Bordeaux, 33076, France
    Recruiting
    • Stéphane Ducassou, M.D. · Principal investigator
  • CHRU Brest - Morvan
    Brest, 29609, France
    Recruiting
    • Liana Carausu, M.D. · Principal investigator
  • Centre Hospitalier Universitaire Caen
    Caen, 14033, France
    Recruiting
    • Damien Bodet, M.D. · Principal investigator
  • CHU Clermont-Ferrand
    Clermont-Ferrand, 63000, France
    Recruiting
    • Justyna Kanold, M.D. · Principal investigator
  • CHU Dijon Hôpital François Mitterrand
    Dijon, 21000, France
    Recruiting
    • Claire Desplantes, M.D. · Principal investigator
  • CHU de Grenoble site Nord - Hôpital Albert Michallon
    Grenoble, 38043, France
    Recruiting
    • Corine Armari Alla · Principal investigator
  • CHRU de Lille - Hôpital Jeanne de Flandre
    Lille, 59037, France
    Recruiting
    • Wadih Abou Chahla, M.D. · Principal investigator
  • Hôpital de la mère et de l'enfant
    Limoges, 87042, France
    Recruiting
    • Christophe Piguet, M.D. · Principal investigator
  • CHU de Lyon HCL - GH Est-Institut d'hématologie et d'oncologie pédiatrique IHOP
    Lyon, 69373, France
    Recruiting
    • Carine Halfon-Domenech, M.D. · Principal investigator
  • CHU de Marseille - Hôpital de la Timone
    Marseille, 13385, France
    Recruiting
    • Paul Saultier, M.D. · Principal investigator
  • CHU de Montpellier - Hôpital Arnaud de Villeneuve
    Montpellier, 34295, France
    Recruiting
    • Stéphanie Haouy, M.D. · Principal investigator
  • CHU Nantes-Hôpital enfant-adolescent
    Nantes, 44093, France
    Recruiting
    • Caroline Thomas, M.D. · Principal investigator
  • CHU Nice - Hôpital l'Archet 2
    Nice, 6200, France
    Recruiting
    • Pierre-Simon Rohrlich, M.D. · Principal investigator
  • CHU Paris Saint Louis
    Paris, 75010, France
    Recruiting
    • Nicolas Boissel, M.D. · Principal investigator
  • CHU Paris Armand Trousseau
    Paris, 75012, France
    Recruiting
    • Arnaud Petit, M.D. · Principal investigator
  • CHU Paris - Hôpital Robert Debré
    Paris, 75019, France
    Recruiting
    • Marion Strullu, M.D. · Principal investigator
  • CHU Poitiers
    Poitiers, 86021, France
    Recruiting
    • Anamaria Stetco · Principal investigator
  • CHU Reims-American Hospital
    Reims, 51100, France
    Recruiting
    • Claire Pluchart, M.D. · Principal investigator
  • CHU Rennes - Hôpital sud
    Rennes, 35203, France
    Recruiting
    • Virginie Gandemer, M.D. · Principal investigator
  • CHU Rouen
    Rouen, 76031, France
    Recruiting
    • Pascale Schneider, M.D. · Principal investigator
  • CHU De La Réunion - Site Nord (Hôpital Félix GUYON)
    Saint-Denis, 97400, France
    Recruiting
    • Yves Reguerre, M.D. · Principal investigator
  • CHU Saint Etienne Hôpital Nord
    Saint-Etienne, 42055, France
    Recruiting
    • Sandrine Thouvenin-Doulet, M.D. · Principal investigator
  • CHU Strasbourg -Hôpital de Hautepierre
    Strasbourg, 67098, France
    Recruiting
    • Catherine Paillard, M.D. · Principal investigator
  • CHU Toulouse
    Toulouse, 31059, France
    Recruiting
    • Marlène Pasquet, M.D. · Principal investigator
  • CHRU Tours- Hôpital Clocheville
    Tours, 37000, France
    Recruiting
    • Julien Lejeune, M.D. · Principal investigator
  • CHU de Nancy - Hôpital de Brabois Enfant
    Vandœuvre-lès-Nancy, 54511, France
    Recruiting
    • Cécile Pochon, M.D. · Principal investigator
  • Evangelisches Klinikum Bethel
    Bielefeld, 33617, Germany
    Recruiting
    • Norbert Jorch, M.D. · Principal investigator
  • Universitätsklinikum Bonn
    Bonn, 53113, Germany
    Recruiting
    • Ina Hainmann · Principal investigator
  • Klinikum Bremen Mitte
    Bremen, 28177, Germany
    Recruiting
    • Arnulf Pekrun, M.D. · Principal investigator
  • Universitätsklinikum Hamburg-Eppendorf
    Hamburg, 20246, Germany
    Recruiting
    • Gabriele Escherich, M.D. · Principal investigator
  • HELIOS Klinikum Krefeld
    Krefeld, 47805, Germany
    Recruiting
    • Thomas Imschweiler, M.D. · Principal investigator
  • Universitätsmedizin Mainz
    Mainz, 55131, Germany
    Recruiting
    • Jörg Faber, M.D. · Principal investigator
  • Landspitali University Hospital, Children's Hospital
    Reykjavik, 101, Iceland
    Recruiting
    • Gauti Rafn Vilbergsson, M.D. · Principal investigator
  • Our Lady's Children's Hospital
    Dublin, Ireland
    Recruiting
    • Owen Smith, M.D. · Principal investigator
  • Children's Hospital, Affiliate of Vilnius University Hospital Santaros Klinikos
    Vilnius, 08661, Lithuania
    Recruiting
    • Goda Vaitkeviciene, M.D. · Principal investigator
  • Princess Máxima Center for Pediatric Oncology
    Utrecht, 3584, Netherlands
    Recruiting
    • Inge van der Sluis, M.D. · Principal investigator
  • University Medical Center Utrecht
    Utrecht, Netherlands
    Recruiting
    • Lotte van der Wagen, M.D. · Principal investigator
  • Haukeland University Hospital, Dept of Haematology
    Bergen, 5021, Norway
    Recruiting
    • Nessar Ahmad Azrakhsh, M.D. · Principal investigator
  • Haukeland University Hospital, Dept of Paediatrics
    Bergen, 5021, Norway
    Recruiting
    • Anita Andrejeva, M.D. · Principal investigator
  • Oslo University Hospital, Dept of Haematology
    Oslo, 0372, Norway
    Recruiting
    • Hilde Skuterud Wik, M.D. · Principal investigator
  • Oslo University Hospital, Dept of paediatric haemato- and oncology
    Oslo, 0424, Norway
    Recruiting
    • Inga Maria Johannsdottir, M.D. · Principal investigator
  • Stavanger University Hospital, Dept of Haematology
    Stavanger, 4011, Norway
    Recruiting
    • Waleed Majeed Mohammed, M.D. · Principal investigator
  • University Hospital North Norway, Dept of Haematology
    Tromsø, 9019, Norway
    Recruiting
    • Lars Horvei, M.D. · Principal investigator
  • University Hospital of North Norway, Dept of Paediatrics
    Tromsø, 9038, Norway
    Recruiting
    • Simon Kranz, M.D. · Principal investigator
  • St. Olavs University Hospital, Dept of Paediatrics
    Trondheim, 7006, Norway
    Recruiting
    • Bendik Lund, M.D. · Principal investigator
  • St. Olavs University Hospital, Dept of Haematology
    Trondheim, 7030, Norway
    Recruiting
    • Petter Quist-Paulsen, M.D. · Principal investigator
  • Centro Hospitalar e Universitário de Coimbra, EPE - Hospital Pediátrico de Coimbra
    Coimbra, 3000-602, Portugal
    Not yet recruiting
    • Manuel Brito, M.D. · Principal investigator
  • Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE
    Lisbon, 1099-023, Portugal
    Recruiting
    • Joaquin Duarte, M.D. · Principal investigator
  • Instituto Português de Oncologia do Porto Francisco Gentil, EPE
    Porto, 4200-072, Portugal
    Recruiting
    • Vitor Costa, M.D. · Principal investigator
  • Hospital Universitario De Cruces
    Barakaldo, Spain
    Not yet recruiting
    • Rosa Maria Adán, M.D. · Principal investigator
  • Hospital Universitari Vall D Hebron
    Barcelona, Spain
    Recruiting
    • Thais Murciano, M.D. · Principal investigator
  • Hospital Sant Joan De Deu Barcelona
    Esplugues de Llobregat, Spain
    Recruiting
    • Jose Luis Dapena, M.D. · Principal investigator
  • Hospital Infantil Universitario Nino Jesus
    Madrid, Spain
    Not yet recruiting
    • Blanca Herrero, M.D. · Principal investigator
  • Hospital Universitario La Paz
    Madrid, Spain
    Not yet recruiting
    • Berta González, M.D. · Principal investigator
  • University Hospital Son Espases
    Palma de Mallorca, Spain
    Not yet recruiting
    • Elena García, M.D. · Principal investigator
  • University Hospital Virgen Del Rocio S.L.
    Seville, Spain
    Not yet recruiting
    • Águeda Molinos, M.D. · Principal investigator
  • Hospital Universitario Y Politecnico La Fe
    Valencia, Spain
    Not yet recruiting
    • Carolina Fuentes, M.D. · Principal investigator
  • Hospital Universitario Miguel Servet
    Zaragoza, Spain
    Not yet recruiting
    • Carmen Rodríguez-Vigil, M.D. · Principal investigator
  • Sahlgrenska University Hospital, Section for Haematology and coagulation
    Gothenburg, 41345, Sweden
    Recruiting
    • Stella Wei, M.D. · Principal investigator
  • Sahlgrenska University Hospital, Dept of Paediatric Haematology and Oncology
    Gothenburg, 41685, Sweden
    Recruiting
    • Jonatan Källström, M.D. · Principal investigator
  • Linköping University Hospital, Dept of Haematology
    Linköping, 58185, Sweden
    Recruiting
    • Thomas Erger, M.D. · Principal investigator
  • Linköping University Hospital, Dept of Paediatrics
    Linköping, 58185, Sweden
    Recruiting
    • Hartmut Vogt, M.D. · Principal investigator
  • Skåne University Hospital, Dept of Haematology
    Lund, 22185, Sweden
    Recruiting
    • Beata Tomaszewska-Toporska, M.D. · Principal investigator
  • Skåne University Hospital, Dept of Paediatrics
    Lund, 22185, Sweden
    Recruiting
    • Anders Castor, M.D. · Principal investigator
  • Örebro University Hospital, Section for Haematology
    Örebro, 70185, Sweden
    Recruiting
    • Erik Ahlstrand, M.D. · Principal investigator
  • Karolinska University Hospital, Dept of Paediatric Oncology and Haematology
    Stockholm, 17176, Sweden
    Recruiting
    • Johan Malmros, M.D. · Principal investigator
  • Karolinska University Hospital, Patient area Haematology
    Stockholm, 17176, Sweden
    Recruiting
    • Joel Joelsson, M.D. · Principal investigator
  • Norrland University Hospital, Dept of Haematology
    Umeå, 90185, Sweden
    Recruiting
    • Antonio Izarra, M.D. · Principal investigator
  • Norrland University Hospital, Dept of Paediatrics
    Umeå, 90185, Sweden
    Recruiting
    • Ulrika Norén Nyström, M.D. · Principal investigator
  • Uppsala University Hospital, Dept of Haematology
    Uppsala, 75185, Sweden
    Recruiting
    • Helene Hallböök, M.D. · Principal investigator
  • Uppsala University Hospital, Dept of Paediatric Haematology and Oncology
    Uppsala, 75185, Sweden
    Recruiting
    • Arja Harila-Saari, M.D. · Principal investigator

Showing the first 100 of 137 sites across 15 countries. Choose a country and city above to see the rest.

08

References and documents

Publications

  • Toft N, Birgens H, Abrahamsson J, Griskevicius L, Hallbook H, Heyman M, Klausen TW, Jonsson OG, Palk K, Pruunsild K, Quist-Paulsen P, Vaitkeviciene G, Vettenranta K, Asberg A, Frandsen TL, Marquart HV, Madsen HO, Noren-Nystrom U, Schmiegelow K. Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia. Leukemia. 2018 Mar;32(3):606-615. doi: 10.1038/leu.2017.265. Epub 2017 Aug 18. PubMed 28819280 ↗
  • Schramm F, Zimmermann M, Jorch N, Pekrun A, Borkhardt A, Imschweiler T, Christiansen H, Faber J, Feuchtinger T, Schmid I, Beron G, Horstmann MA, Escherich G. Daunorubicin during delayed intensification decreases the incidence of infectious complications - a randomized comparison in trial CoALL 08-09. Leuk Lymphoma. 2019 Jan;60(1):60-68. doi: 10.1080/10428194.2018.1473575. Epub 2018 Jul 3. PubMed 29966458 ↗
  • Mondelaers V, Suciu S, De Moerloose B, Ferster A, Mazingue F, Plat G, Yakouben K, Uyttebroeck A, Lutz P, Costa V, Sirvent N, Plouvier E, Munzer M, Poiree M, Minckes O, Millot F, Plantaz D, Maes P, Hoyoux C, Cave H, Rohrlich P, Bertrand Y, Benoit Y; Children-s Leukemia Group (CLG) of the European Organization for Research and Treatment of Cancer (EORTC). Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951. Haematologica. 2017 Oct;102(10):1727-1738. doi: 10.3324/haematol.2017.165845. Epub 2017 Jul 27. PubMed 28751566 ↗
  • Vora A, Goulden N, Wade R, Mitchell C, Hancock J, Hough R, Rowntree C, Richards S. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013 Mar;14(3):199-209. doi: 10.1016/S1470-2045(12)70600-9. Epub 2013 Feb 7. PubMed 23395119 ↗
  • Pieters R, de Groot-Kruseman H, Van der Velden V, Fiocco M, van den Berg H, de Bont E, Egeler RM, Hoogerbrugge P, Kaspers G, Van der Schoot E, De Haas V, Van Dongen J. Successful Therapy Reduction and Intensification for Childhood Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring: Study ALL10 From the Dutch Childhood Oncology Group. J Clin Oncol. 2016 Aug 1;34(22):2591-601. doi: 10.1200/JCO.2015.64.6364. Epub 2016 Jun 6. PubMed 27269950 ↗
  • Toksvang LN, Als-Nielsen B, Bacon C, Bertasiute R, Duarte X, Escherich G, Helgadottir EA, Johannsdottir IR, Jonsson OG, Kozlowski P, Langenskjold C, Lepik K, Niinimaki R, Overgaard UM, Punab M, Raty R, Segers H, van der Sluis I, Smith OP, Strullu M, Vaitkeviciene G, Wik HS, Heyman M, Schmiegelow K. Thiopurine Enhanced ALL Maintenance (TEAM): study protocol for a randomized study to evaluate the improvement in disease-free survival by adding very low dose 6-thioguanine to 6-mercaptopurine/methotrexate-based maintenance therapy in pediatric and adult patients (0-45 years) with newly diagnosed B-cell precursor or T-cell acute lymphoblastic leukemia treated according to the intermediate risk-high group of the ALLTogether1 protocol. BMC Cancer. 2022 May 2;22(1):483. doi: 10.1186/s12885-022-09522-3. PubMed 35501736 ↗

Individual participant data

Plan to share: Yes — ALLTogether Data Sharing Policy FINAL VERSION 1.0 DATED 12APRIL2022 applies (full details available from Trial Central Office): Policy The ALLTogether Consortium aims to maximise the availability of research data to the academic community for academic non-commercial research purposes with as few restrictions as possible. All research papers should be open access whenever possible. Clinical data: The ALLTogether Consortium will consider requests for individual participant data (IPD) that underlie published results after deidentification. Requests for access for unpublished data will also be considered on a case-by-case basis. ALLTogether scientific data underpinning basic science/translational research papers should be made available to other researchers in the ALLTogether consortium and requests from academic researchers outside the consortium for access to scientific datasets should be addressed to the lead investigator of the ALLTogether study.

Supporting information: Study protocol, Statistical analysis plan

Time frame: The ALLTogether Consortium will consider requests for individual participant data (IPD) that underlie published results after deidentification. Requests for access for unpublished data will also be considered on a case-by-case basis.

Access criteria: Data access requests will be reviewed by The ALLTogether Board and, when applicable the ALLTogether Scientific committee. IPD will only be released if all personalised identifiers can be removed and for the sole use of the approved request (tertiary dissemination will not be permitted). Requestors will be required to sign a Data Access Agreement.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Jul 2020 (actual). Primary completion is estimated for Jun 2033, 155 months after the start.

Of 43 non-industry phase 3 interventional studies under Precursor Cell Lymphoblastic Leukemia-Lymphoma, half reached primary completion within 95 months of starting (the median), counting those still running; a quarter within 65 and three quarters within 109. This study's planned 155 months is above that.

Counting every sponsor, half of 59 studies reached it within 86 months; a quarter within 46 and three quarters within 104.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 5, 2020
First posted
Mar 13, 2020
StartActual
Jul 13, 2020
Primary completionEst.
Jun 2033
CompletionEst.
Jun 2033
Last update
Aug 12, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Aug 12, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04307576
Lead sponsor
Mats Heyman
Collaborators
The Swedish Research Council, The Swedish Childhood Cancer Foundation, Pfizer, Servier, NordForsk, Aamu Pediatric Cancer Foundation, German Society for Pediatric Oncology and Hematology GPOH gGmbH, Clinical Trial Center North (CTC North GmbH & Co. KG), Belgium Health Care Knowledge Centre, Karolinska Institutet, Cancer Research UK, Fundação Rui Osório de Castro, Acreditar - Associação de Pais e Amigos das Crianças com Cancro, Grupo Português De Leucemias Pediátricas, Amgen, Nova Laboratories Limited, Danish Child Cancer Foundation, Danish Cancer Society, The Novo Nordic Foundation, Assistance Publique - Hôpitaux de Paris, Direction Générale de l'Offre de Soins, Swedish Cancer Society
Responsible party
Mats Heyman (MD, Associate Professor, Karolinska University Hospital) — Sponsor-investigator
First posted
Mar 13, 2020
Start date
Jul 13, 2020
Primary completion
Jun 2033 (estimated)
Completion
Jun 2033 (estimated)
Last update
Aug 12, 2026

Study contacts

Global Clinical Trial Manager ALLTogether1
Contact
alltogether.karolinska@regionstockholm.se
+46 8 123 700 00
Mats Heyman, MD, PhD
study chair · Karolinska University Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Imatinib · Blinatumomab

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