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

NCT03911128 | Recruiting

• 1 other identifier: ALLTogether1 pilot
• Study Type: observational
• Target: 500
• Locations: 7 countries
• Sites: 50

Brief Summary

The pilot study 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 platform 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 trials included in the study-design. The pilot study is implemented as a master protocol without study specific interventions, thus as an observational study. The pilot study is for countries/study-groups who intend to join ALLTogether1 (including experimental interventions). For these countries the pilot study is crucial to optimise diagnostics, registration systems, collaborations with vendors, logistics and data-checks before starting the main study. The study only includes "standard of care" treatment included in the master protocol.

Conditions

Leukemia, Acute Lymphoblastic

Keywords

Leukemia; Acute Lymphoblastic; ALL; ALLTogether; Leukaemia

Outcome Measures

Primary Outcomes (2)

• Event-free survival (EFS) compared to historical controls

  5 year

• Overall survival (OS) compared to historical controls

  5 year

Study Arms (1)

Participants with newly diagnosed ALL

Other: Observational

Interventions

Observational OTHER

Observational study - no intervention

Participants with newly diagnosed ALL

Eligibility Criteria

• Age: 0 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Participants 0-45 years with newly diagnosed acute lymphoblastic leukaemia. The protocol has no gender-bias. The total estimated recruitment in the pilot study is 500 participants.

You may qualify if:

• Patients newly diagnosed with T-lymphoblastic (T-cell) or B-lymphoblastic precursor (BCP) leukaemia (ALL) according to the WHO-classification of Tumours of Haematopoietic 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.

You may not qualify if:

• 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 and patients who intend to stay at least for the duration of the treatment 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.
• Age \< 365 days and KMT2A-rearranged (KMT2A-r) BCP-ALL (documented presence of a KMT2A-split by FISH and/or a KMT2A fusion transcript). These patients will be transferred to an appropriate trial for infant KMT2A-r BCP-ALL, if available.
• 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::ABL1 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).

Sponsors & Collaborators

• Mats Heyman: lead
• Nordic Society for Pediatric Hematology and Oncology: collaborator
• The Swedish Childhood Cancer Foundation: collaborator
• NordForsk: collaborator

Study Sites (53)

Aalborg University Hospital, Dept of Paediatrics

Aalborg, 9000, Denmark

ACTIVE NOT RECRUITING

Aarhus University Hospital

Aarhus, 8000, Denmark

ACTIVE NOT RECRUITING

Aarhus University Hospital, Child and Adolescent Health

Aarhus, 8200, Denmark

ACTIVE NOT RECRUITING

Rigshospitalet, Dept of Haematology

Copenhagen, 2100, Denmark

ACTIVE NOT RECRUITING

Rigshospitalet, Dept of Paediatrics

Copenhagen, 2100, Denmark

ACTIVE NOT RECRUITING

Odense University Hospital, Dept of Paediatrics

Odense, 5000, Denmark

ACTIVE NOT RECRUITING

North Estonia Medical Centre, Dept of Haematology

Tallinn, 13419, Estonia

NOT YET RECRUITING

Tallinn Children´s Hospital, Dept of Paediatrics

Tallinn, 13419, Estonia

NOT YET RECRUITING

Tartu University Hospital

Tartu, 50406, Estonia

NOT YET RECRUITING

Helsinki University Hospital, Dept of Haematology

Helsinki, 00029, Finland

ACTIVE NOT RECRUITING

Helsinki University Hospital, Dept of Paediatrics

Helsinki, 00029, Finland

ACTIVE NOT RECRUITING

Kuopio University Hospital, Dept of Haematology

Kuopio, 70029, Finland

ACTIVE NOT RECRUITING

Kuopio University Hospital, Dept of Paediatrics

Kuopio, 70029, Finland

ACTIVE NOT RECRUITING

Oulu University Hospital, Dept of Haematology, Dept of Medicine

Oulu, 90029, Finland

NOT YET RECRUITING

Oulu University Hospital, Dept of Paediatrics

Oulu, 90029, Finland

ACTIVE NOT RECRUITING

Tampere University Hospital, Dept of Haematology

Tampere, 33521, Finland

NOT YET RECRUITING

Tampere University Hospital, Dept of Paediatrics

Tampere, 33521, Finland

ACTIVE NOT RECRUITING

Turku University Hospital, Clinical Haematology and Stem Cell Transplantation Unit

Turku, 20520, Finland

NOT YET RECRUITING

Turku University Hospital, Dept of Paediatrics

Turku, 20520, Finland

ACTIVE NOT RECRUITING

Landspitali University Hospital, Children's Hospital

Reykjavik, 101, Iceland

ACTIVE NOT RECRUITING

Children's Hospital, Affiliate of Vilnius University Hospital

Vilnius, 08406, Lithuania

ACTIVE NOT RECRUITING

Vilnius University Hospital

Vilnius, 08661, Lithuania

ACTIVE NOT RECRUITING

Haukeland University Hospital, Dept of Haematology

Bergen, 5021, Norway

ACTIVE NOT RECRUITING

Haukeland University Hospital, Dept of Paediatrics

Bergen, 5021, Norway

ACTIVE NOT RECRUITING

Oslo University Hospital, Dept of Haematology

Oslo, 0372, Norway

ACTIVE NOT RECRUITING

Oslo University Hospital, Dept of paediatric haemato- and oncology

Oslo, 0424, Norway

ACTIVE NOT RECRUITING

Stavanger University Hospital, Dept of Haematology

Stavanger, 4011, Norway

ACTIVE NOT RECRUITING

University Hospital North Norway, Dept of Haematology

Tromsø, 9019, Norway

ACTIVE NOT RECRUITING

University Hospital of North Norway, Dept of Paediatrics

Tromsø, 9038, Norway

ACTIVE NOT RECRUITING

St. Olavs University Hospital, Dept of Paediatrics

Trondheim, 7006, Norway

ACTIVE NOT RECRUITING

St. Olavs University Hospital, Dept of Haematology

Trondheim, 7030, Norway

ACTIVE NOT RECRUITING

Hospital Universitario de Cruces

Barakaldo, Spain

RECRUITING

Hospital Universitario San Joan de Déu

Barcelona, Spain

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, Spain

RECRUITING

Hospital Universitario La Paz

Fuencarral-El Pardo, Spain

RECRUITING

Hospital Infantil Universitario Nino Jesus

Madrid, Spain

RECRUITING

Hospital Universitario Son Espases

Palma de Mallorca, Spain

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, Spain

RECRUITING

Hospital Universitario Politécnico La Fe

Valencia, Spain

RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, Spain

RECRUITING

Sahlgrenska University Hospital, Section for Haematology and coagulation

Gothenburg, 41345, Sweden

ACTIVE NOT RECRUITING

Sahlgrenska University Hospital, Dept of Paediatric Haematology and Oncology

Gothenburg, 41685, Sweden

ACTIVE NOT RECRUITING

Linköping University Hospital, Dept of Haematology

Linköping, 58185, Sweden

ACTIVE NOT RECRUITING

Linköping University Hospital, Dept of Paediatrics

Linköping, 58185, Sweden

ACTIVE NOT RECRUITING

Skåne University Hospital, Dept of Haematology

Lund, 22185, Sweden

ACTIVE NOT RECRUITING

Skåne University Hospital, Dept of Paediatrics

Lund, 22185, Sweden

ACTIVE NOT RECRUITING

Örebro University Hospital, Section for Haematology

Örebro, 70185, Sweden

ACTIVE NOT RECRUITING

Karolinska University Hospital, Dept of Paediatric Oncology and Haematology

Stockholm, 17176, Sweden

ACTIVE NOT RECRUITING

Karolinska University Hospital, Patient area Haematology

Stockholm, 17176, Sweden

ACTIVE NOT RECRUITING

Norrland University Hospital, Dept of Haematology

Umeå, 90185, Sweden

ACTIVE NOT RECRUITING

Norrland University Hospital, Dept of Paediatrics

Umeå, 90185, Sweden

ACTIVE NOT RECRUITING

Uppsala University Hospital, Dept of Haematology

Uppsala, 75185, Sweden

ACTIVE NOT RECRUITING

Uppsala University Hospital, Dept of Paediatric Haematology and Oncology

Uppsala, 75185, Sweden

ACTIVE NOT RECRUITING

Related Publications (6)

• 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.

  PMID: 28819280 BACKGROUND

• 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.

  PMID: 29966458 BACKGROUND

• 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.

  PMID: 28751566 BACKGROUND

• 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.

  PMID: 23395119 BACKGROUND

• 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.

  PMID: 27269950 BACKGROUND

• Fermer J, van Bunningen H, Zhou O, Abrahamsson J, Borssen M, Donner I, Heyman M, Holmqvist AS, Valind A, Vogt H, Ranta S, Harila A. Early Toxicity in Childhood Acute Lymphoblastic Leukemia: A Comparison of NOPHO ALL2008 and ALLTogether Protocols in Sweden. Pediatr Blood Cancer. 2025 Nov 20:e32168. doi: 10.1002/pbc.32168. Online ahead of print.

  PMID: 41262029 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

* Blood/blood plasma * Cerebrospinal fluid * Bone marrow

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Mats Heyman, M.D. PhD

  Karolinska University Hospital

  STUDY CHAIR

Central Study Contacts

Trial Central Office

CONTACT

+46812370000; alltogether.karolinska@regionstockholm.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Associate Professor

Study Record Dates

• First Submitted: March 26, 2019
• First Posted: April 10, 2019
• Study Start: August 29, 2019
• Primary Completion (Estimated): June 1, 2033
• Study Completion (Estimated): June 1, 2033
• Last Updated: September 2, 2025

Record last verified: 2025-08

Locations

ES (9); IC (1); LI (2); FI (10); DK (6); SE (13); NO (9)