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

ConditionLeukemia, Acute Lymphoblastic

Trial statusRecruiting

Trial phasePhase 3

Trial typeInterventional

Biological sexAll

Age0-45

SponsorMats Heyman

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

Omitted Doxorubicin
Drug
Omission of IV Doxorubicin
Omitted Vincristine+Dexamethasone pulses
Drug
Omission of Vincristine+Dexamethasone pulses
Inotuzumab Ozogamicin+Standard Maintenance Therapy
Drug
Addition of IV Inotuzumab ozogamicin before Maintenance Therapy
Imatinib
Drug
p.o. Imatinib
6-tioguanine+Standard Maintenance Therapy
Drug
Addition of p.o. 6-tioguanine to Standard Maintenance Therapy
Blinatumomab
Drug
IV Blinatumomab

Treatment groups

6,430 Participants

are divided into 10 treatment groups

Treatment groups

See each treatment group below.

Group A: R1 - SR standard armNo intervention 0 interventions

Group B: R1 - SR experimental armExperimental treatment 1 intervention

Group C: R2 - IR-low standard armNo intervention 0 interventions

Group D: R2 - IR-low experimental arm AExperimental treatment 1 intervention

Group E: R3 - IR-high standard armNo intervention 0 interventions

Group F: R3-InO - IR-high experimental armExperimental treatment 1 intervention

Group G: ABL-class fusions interventionExperimental treatment 1 intervention

Group H: R3-TEAM - IR-high experimental armExperimental treatment 1 intervention

Group I: ALLTogether1 DS Blinatumomab interventionExperimental treatment 1 intervention

Group J: R2 - IR-low experimental arm BExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

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.

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).

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.

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

Secondary outcomes

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.

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.

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

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

Other outcomes

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)

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)

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mats Heyman

Lead sponsor

Karolinska University Hospital

Sponsor institution

The Swedish Research Council

Collaborator

The Swedish Childhood Cancer Foundation

Collaborator

Pfizer

Collaborator

Servier

Collaborator

NordForsk

Collaborator

Aamu Pediatric Cancer Foundation

Collaborator

German Society for Pediatric Oncology and Hematology GPOH gGmbH

Collaborator

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

Collaborator

Belgium Health Care Knowledge Centre

Collaborator

Karolinska Institutet

Collaborator

Cancer Research UK

Collaborator

Fundação Rui Osório de Castro

Collaborator

Acreditar - Associação de Pais e Amigos das Crianças com Cancro

Collaborator

Grupo Português De Leucemias Pediátricas

Collaborator

Amgen

Collaborator

Nova Laboratories Limited

Collaborator

Danish Child Cancer Foundation

Collaborator

Danish Cancer Society

Collaborator

The Novo Nordic Foundation

Collaborator

Assistance Publique - Hôpitaux de Paris

Collaborator

Direction Générale de l'Offre de Soins

Collaborator

Swedish Cancer Society

Collaborator

Source ClinicalTrials.gov

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