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

NCT ID: NCT04307576

Last Updated: 2025-08-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 6430 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-13
• Study Completion Date: 2033-06-30

Brief 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.

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.

Conditions

Leukemia, Acute Lymphoblastic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

R1 - SR standard arm

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

R1 - SR experimental arm

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

Group Type: EXPERIMENTAL

Omitted Doxorubicin

Intervention Type: DRUG

Omission of IV Doxorubicin

R2 - IR-low standard arm

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

R2 - IR-low experimental arm A

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

Group Type: EXPERIMENTAL

Omitted Doxorubicin

Intervention Type: DRUG

Omission of IV Doxorubicin

R3 - IR-high standard arm

Intermediate risk high arm receiving Standard Maintenance Therapy.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

Inotuzumab Ozogamicin+Standard Maintenance Therapy

Intervention Type: DRUG

Addition of IV Inotuzumab ozogamicin before Maintenance Therapy

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.

Group Type: EXPERIMENTAL

Imatinib

Intervention Type: DRUG

p.o. Imatinib

R3-TEAM - IR-high experimental arm

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

Group Type: EXPERIMENTAL

6-tioguanine+Standard Maintenance Therapy

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Blinatumomab

Intervention Type: DRUG

IV Blinatumomab

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.

Group Type: EXPERIMENTAL

Omitted Vincristine+Dexamethasone pulses

Intervention Type: DRUG

Omission of Vincristine+Dexamethasone pulses

Interventions

Omitted Doxorubicin

Omission of IV Doxorubicin

Intervention Type: DRUG

Omitted Vincristine+Dexamethasone pulses

Omission of Vincristine+Dexamethasone pulses

Intervention Type: DRUG

Inotuzumab Ozogamicin+Standard Maintenance Therapy

Addition of IV Inotuzumab ozogamicin before Maintenance Therapy

Intervention Type: DRUG

Imatinib

p.o. Imatinib

Intervention Type: DRUG

6-tioguanine+Standard Maintenance Therapy

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

Intervention Type: DRUG

Blinatumomab

IV Blinatumomab

Intervention Type: DRUG

Other Intervention Names

Besponsa+Maintenance Therapy; Blincyto

Eligibility Criteria

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.
• Informed consent 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 childbearing potential (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

• 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 corticosteroids 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 contraindications 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 childbearing potential 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 contraception 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.

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Swedish Research Council

OTHER_GOV

Sponsor Role: collaborator

The Swedish Childhood Cancer Foundation

UNKNOWN

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: collaborator

Servier

INDUSTRY

Sponsor Role: collaborator

NordForsk

UNKNOWN

Sponsor Role: collaborator

Aamu Pediatric Cancer Foundation

UNKNOWN

Sponsor Role: collaborator

German Society for Pediatric Oncology and Hematology GPOH gGmbH

OTHER

Sponsor Role: collaborator

Clinical Trial Center North (CTC North GmbH & Co. KG)

OTHER

Sponsor Role: collaborator

Belgium Health Care Knowledge Centre

OTHER_GOV

Sponsor Role: collaborator

Karolinska Institutet

OTHER

Sponsor Role: collaborator

Cancer Research UK

OTHER

Sponsor Role: collaborator

Fundação Rui Osório de Castro

UNKNOWN

Sponsor Role: collaborator

Acreditar - Associação de Pais e Amigos das Crianças com Cancro

UNKNOWN

Sponsor Role: collaborator

Grupo Português De Leucemias Pediátricas

UNKNOWN

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: collaborator

Nova Laboratories Limited

INDUSTRY

Sponsor Role: collaborator

Danish Child Cancer Foundation

OTHER

Sponsor Role: collaborator

Danish Cancer Society

OTHER

Sponsor Role: collaborator

The Novo Nordic Foundation

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: collaborator

Direction Générale de l'Offre de Soins

OTHER_GOV

Sponsor Role: collaborator

Swedish Cancer Society

OTHER

Sponsor Role: collaborator

Mats Heyman

OTHER

Sponsor Role: lead

Responsible Party

Mats Heyman

MD, Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mats Heyman, MD, PhD

Role: STUDY_CHAIR

Karolinska University Hospital

Locations

L'hôpital Universitaire des enfants Reine Fabiola (Huderf)

Brussels, , Belgium

Site Status: RECRUITING

Cliniques Universitaires Saint-Luc (UCL)

Brussels, , Belgium

Site Status: RECRUITING

University Hospital Antwerp

Edegem, , Belgium

Site Status: RECRUITING

University Hospital Ghent

Ghent, , Belgium

Site Status: RECRUITING

University Hospital Leuven, Dept of Paediatrics

Leuven, , Belgium

Site Status: RECRUITING

CHC MontLégia, Boulevard Patience et Beaujonc 2

Liège, , Belgium

Site Status: RECRUITING

CHR de la Citadelle

Liège, , Belgium

Site Status: RECRUITING

Aalborg University Hospital, Dept of Paediatrics

Aalborg, , Denmark

Site Status: RECRUITING

Aarhus University Hospital

Aarhus, , Denmark

Site Status: RECRUITING

Aarhus University Hospital, Child and Adolescent Health

Aarhus, , Denmark

Site Status: RECRUITING

Rigshospitalet, Dept of Haematology

Copenhagen, , Denmark

Site Status: RECRUITING

Rigshospitalet, Dept of Paediatrics

Copenhagen, , Denmark

Site Status: RECRUITING

Odense University Hospital, Dept of Paediatrics

Odense, , Denmark

Site Status: RECRUITING

North Estonia Medical Centre, Dept of Haematology

Tallinn, , Estonia

Site Status: RECRUITING

Tallinn Children´s Hospital, Dept of Paediatrics

Tallinn, , Estonia

Site Status: RECRUITING

Tartu University Hospital

Tartu, , Estonia

Site Status: RECRUITING

Helsinki University Hospital, Dept of Haematology

Helsinki, , Finland

Site Status: RECRUITING

Helsinki University Hospital, Dept of Paediatrics

Helsinki, , Finland

Site Status: RECRUITING

Kuopio University Hospital, Dept of Haematology

Kuopio, , Finland

Site Status: RECRUITING

Kuopio University Hospital, Dept of Paediatrics

Kuopio, , Finland

Site Status: RECRUITING

Oulu University Hospital, Dept of Haematology, Dept of Medicine

Oulu, , Finland

Site Status: RECRUITING

Oulu University Hospital, Dept of Paediatrics

Oulu, , Finland

Site Status: RECRUITING

Tampere University Hospital, Dept of Haematology

Tampere, , Finland

Site Status: RECRUITING

Tampere University Hospital, Dept of Paediatrics

Tampere, , Finland

Site Status: RECRUITING

Turku University Hospital, Clinical Haematology and Stem Cell Transplantation Unit

Turku, , Finland

Site Status: RECRUITING

Turku University Hospital, Dept of Paediatrics

Turku, , Finland

Site Status: RECRUITING

CHU Amiens Groupe Hospitalier Sud

Amiens, , France

Site Status: RECRUITING

CHU Angers

Angers, , France

Site Status: RECRUITING

CHRU Besançon

Besançon, , France

Site Status: RECRUITING

CHU Bordeaux - Groupe Hospitalier Pellegrin

Bordeaux, , France

Site Status: RECRUITING

CHRU Brest - Morvan

Brest, , France

Site Status: RECRUITING

Centre Hospitalier Universitaire Caen

Caen, , France

Site Status: RECRUITING

CHU Clermont-Ferrand

Clermont-Ferrand, , France

Site Status: RECRUITING

CHU Dijon Hôpital François Mitterrand

Dijon, , France

Site Status: RECRUITING

CHU de Grenoble site Nord - Hôpital Albert Michallon

Grenoble, , France

Site Status: RECRUITING

CHRU de Lille - Hôpital Jeanne de Flandre

Lille, , France

Site Status: RECRUITING

Hôpital de la mère et de l'enfant

Limoges, , France

Site Status: RECRUITING

CHU de Lyon HCL - GH Est-Institut d'hématologie et d'oncologie pédiatrique IHOP

Lyon, , France

Site Status: RECRUITING

CHU de Marseille - Hôpital de la Timone

Marseille, , France

Site Status: RECRUITING

CHU de Montpellier - Hôpital Arnaud de Villeneuve

Montpellier, , France

Site Status: RECRUITING

CHU Nantes-Hôpital enfant-adolescent

Nantes, , France

Site Status: RECRUITING

CHU Nice - Hôpital l'Archet 2

Nice, , France

Site Status: RECRUITING

CHU Paris Saint Louis

Paris, , France

Site Status: RECRUITING

CHU Paris Armand Trousseau

Paris, , France

Site Status: RECRUITING

CHU Paris - Hôpital Robert Debré

Paris, , France

Site Status: RECRUITING

CHU Poitiers

Poitiers, , France

Site Status: RECRUITING

CHU Reims-American Hospital

Reims, , France

Site Status: RECRUITING

CHU Rennes - Hôpital sud

Rennes, , France

Site Status: RECRUITING

CHU Rouen

Rouen, , France

Site Status: RECRUITING

CHU De La Réunion - Site Nord (Hôpital Félix GUYON)

Saint-Denis, , France

Site Status: RECRUITING

CHU Saint Etienne Hôpital Nord

Saint-Etienne, , France

Site Status: RECRUITING

CHU Strasbourg -Hôpital de Hautepierre

Strasbourg, , France

Site Status: RECRUITING

CHU Toulouse

Toulouse, , France

Site Status: RECRUITING

CHRU Tours- Hôpital Clocheville

Tours, , France

Site Status: RECRUITING

CHU de Nancy - Hôpital de Brabois Enfant

Vandœuvre-lès-Nancy, , France

Site Status: RECRUITING

Evangelisches Klinikum Bethel

Bielefeld, , Germany

Site Status: RECRUITING

Universitätsklinikum Bonn

Bonn, , Germany

Site Status: RECRUITING

Klinikum Bremen Mitte

Bremen, , Germany

Site Status: RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status: RECRUITING

HELIOS Klinikum Krefeld

Krefeld, , Germany

Site Status: RECRUITING

Universitätsmedizin Mainz

Mainz, , Germany

Site Status: RECRUITING

Landspitali University Hospital, Children's Hospital

Reykjavik, , Iceland

Site Status: RECRUITING

Our Lady's Children's Hospital

Dublin, , Ireland

Site Status: RECRUITING

Children's Hospital, Affiliate of Vilnius University Hospital Santaros Klinikos

Vilnius, , Lithuania

Site Status: RECRUITING

Vilnius University Hospital Santaros Klinikos

Vilnius, , Lithuania

Site Status: NOT_YET_RECRUITING

Princess Máxima Center for Pediatric Oncology

Utrecht, , Netherlands

Site Status: RECRUITING

University Medical Center Utrecht

Utrecht, , Netherlands

Site Status: RECRUITING

Haukeland University Hospital, Dept of Haematology

Bergen, , Norway

Site Status: RECRUITING

Haukeland University Hospital, Dept of Paediatrics

Bergen, , Norway

Site Status: RECRUITING

Oslo University Hospital, Dept of Haematology

Oslo, , Norway

Site Status: RECRUITING

Oslo University Hospital, Dept of paediatric haemato- and oncology

Oslo, , Norway

Site Status: RECRUITING

Stavanger University Hospital, Dept of Haematology

Stavanger, , Norway

Site Status: RECRUITING

University Hospital North Norway, Dept of Haematology

Tromsø, , Norway

Site Status: RECRUITING

University Hospital of North Norway, Dept of Paediatrics

Tromsø, , Norway

Site Status: RECRUITING

St. Olavs University Hospital, Dept of Paediatrics

Trondheim, , Norway

Site Status: RECRUITING

St. Olavs University Hospital, Dept of Haematology

Trondheim, , Norway

Site Status: RECRUITING

Centro Hospitalar e Universitário de Coimbra, EPE - Hospital Pediátrico de Coimbra

Coimbra, , Portugal

Site Status: NOT_YET_RECRUITING

Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE

Lisbon, , Portugal

Site Status: RECRUITING

Instituto Português de Oncologia do Porto Francisco Gentil, EPE

Porto, , Portugal

Site Status: RECRUITING

Sahlgrenska University Hospital, Section for Haematology and coagulation

Gothenburg, , Sweden

Site Status: RECRUITING

Sahlgrenska University Hospital, Dept of Paediatric Haematology and Oncology

Gothenburg, , Sweden

Site Status: RECRUITING

Linköping University Hospital, Dept of Haematology

Linköping, , Sweden

Site Status: RECRUITING

Linköping University Hospital, Dept of Paediatrics

Linköping, , Sweden

Site Status: RECRUITING

Skåne University Hospital, Dept of Haematology

Lund, , Sweden

Site Status: RECRUITING

Skåne University Hospital, Dept of Paediatrics

Lund, , Sweden

Site Status: RECRUITING

Örebro University Hospital, Section for Haematology

Örebro, , Sweden

Site Status: RECRUITING

Karolinska University Hospital, Dept of Paediatric Oncology and Haematology

Stockholm, , Sweden

Site Status: RECRUITING

Karolinska University Hospital, Patient area Haematology

Stockholm, , Sweden

Site Status: RECRUITING

Norrland University Hospital, Dept of Haematology

Umeå, , Sweden

Site Status: RECRUITING

Norrland University Hospital, Dept of Paediatrics

Umeå, , Sweden

Site Status: RECRUITING

Uppsala University Hospital, Dept of Haematology

Uppsala, , Sweden

Site Status: RECRUITING

Uppsala University Hospital, Dept of Paediatric Haematology and Oncology

Uppsala, , Sweden

Site Status: RECRUITING

Aberdeen Royal Infirmary, Aberdeen

Aberdeen, , United Kingdom

Site Status: NOT_YET_RECRUITING

Royal Aberdeen Children's Hospital, Aberdeen

Aberdeen, , United Kingdom

Site Status: RECRUITING

Royal Belfast Hospital for Sick Children, Belfast

Belfast, , United Kingdom

Site Status: NOT_YET_RECRUITING

Belfast City Hospital, Belfast

Belfast, , United Kingdom

Site Status: NOT_YET_RECRUITING

The Queen Elizabeth Hospital, Birmingham

Birmingham, , United Kingdom

Site Status: RECRUITING

Birmingham Children's Hospital, Birmingham

Birmingham, , United Kingdom

Site Status: RECRUITING

Bristol Royal Hospital for Children / Bristol Haematology and Oncology Centre

Bristol, , United Kingdom

Site Status: RECRUITING

Addenbrooke's Hospital, Cambridge

Cambridge, , United Kingdom

Site Status: RECRUITING

Noah's Ark Children's Hospital for Wales, Cardiff

Cardiff, , United Kingdom

Site Status: NOT_YET_RECRUITING

University Hospital of Wales, Cardiff

Cardiff, , United Kingdom

Site Status: NOT_YET_RECRUITING

Ninewells Hospital, Dundee

Dundee, , United Kingdom

Site Status: NOT_YET_RECRUITING

Western General Hospital, Edinburgh

Edinburgh, , United Kingdom

Site Status: NOT_YET_RECRUITING

Royal Hospital for Children and Young People, Edinburgh

Edinburgh, , United Kingdom

Site Status: RECRUITING

Beatson West of Scotland Cancer Centre, Glasgow

Glasgow, , United Kingdom

Site Status: NOT_YET_RECRUITING

Royal Hospital for Children, Glasgow

Glasgow, , United Kingdom

Site Status: RECRUITING

Leeds General Infirmary, Leeds

Leeds, , United Kingdom

Site Status: RECRUITING

Leeds St James University Hospital

Leeds, , United Kingdom

Site Status: RECRUITING

Leicester Royal Infirmary, Leicester

Leicester, , United Kingdom

Site Status: RECRUITING

Alder Hey Children's Hospital, Liverpool

Liverpool, , United Kingdom

Site Status: RECRUITING

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, , United Kingdom

Site Status: RECRUITING

University College London Hospital, London

London, , United Kingdom

Site Status: RECRUITING

Great Ormond Street Hospital for Children, London

London, , United Kingdom

Site Status: RECRUITING

King's College Hospital

London, , United Kingdom

Site Status: RECRUITING

St. Bartholomews Hospital

London, , United Kingdom

Site Status: RECRUITING

Royal Manchester Children's Hospital, Manchester

Manchester, , United Kingdom

Site Status: RECRUITING

The Christie NHS Foundation Trust (PTC)

Manchester, , United Kingdom

Site Status: RECRUITING

Freeman Hospital, Newcastle

Newcastle, , United Kingdom

Site Status: NOT_YET_RECRUITING

Royal Victoria Infirmary, Newcastle

Newcastle upon Tyne, , United Kingdom

Site Status: RECRUITING

Nottingham City Hospital

Nottingham, , United Kingdom

Site Status: NOT_YET_RECRUITING

Nottingham Queen's Medical Centre

Nottingham, , United Kingdom

Site Status: RECRUITING

Churchill Hospital, Oxford

Oxford, , United Kingdom

Site Status: NOT_YET_RECRUITING

John Radcliffe Hospital, Oxford

Oxford, , United Kingdom

Site Status: RECRUITING

Derriford Hospital

Plymouth, , United Kingdom

Site Status: RECRUITING

Royal Hallamshire Hospital, Sheffield

Sheffield, , United Kingdom

Site Status: RECRUITING

Sheffield Children's Hospital, Sheffield

Sheffield, , United Kingdom

Site Status: RECRUITING

Southampton General Hospital, Southampton

Southampton, , United Kingdom

Site Status: RECRUITING

Royal Stoke University Hospital, Stoke

Stoke, , United Kingdom

Site Status: NOT_YET_RECRUITING

Royal Marsden Hospital, Sutton

Sutton, , United Kingdom

Site Status: RECRUITING

Countries

Belgium; Denmark; Estonia; Finland; France; Germany; Iceland; Ireland; Lithuania; Netherlands; Norway; Portugal; Sweden; United Kingdom

Central Contacts

Global Clinical Trial Manager ALLTogether1

Role: CONTACT

alltogether.karolinska@regionstockholm.se

+46 8 123 700 00

References

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.

Reference Type: BACKGROUND

PMID: 28819280 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29966458 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28751566 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23395119 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27269950 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35501736 (View on PubMed)

Other Identifiers

ALLTogether1

Identifier Type: -

Identifier Source: org_study_id