A Treatment Protocol for Participants 0-45 Years With Acute Lymphoblastic Leukaemia
- Conditions
- Leukemia, Acute Lymphoblastic
- Interventions
- Other: Observational
- Registration Number
- NCT03911128
- Lead Sponsor
- Mats Heyman
- 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.
- Detailed Description
The aims of the ALLTogether study are to improve survival and quality of survival for children and young adults with ALL. ALL in young people has excellent outcome with \>90% survival in children and about 75% in young adults. However, patients still die of disease - after relapse as a result of under-treatment.
Furthermore, a considerable fraction of younger patients are over-treated: All patients risk treatment-related death and some suffer long-term side-effects or secondary cancer. The rates of death from disease and death from therapy are almost the same for children. To show improvement with such good survival, large populations are needed.
Study groups from the five Nordic countries, Estonia and Lithuania (NOPHO), the UK (UKALL), the Netherlands (DCOG), Germany (COALL), Belgium (BSPHO), Ireland (PHOAI), Portugal (SHOP) and France (SFCE) have designed a common treatment protocol as new standard of care for children and young adults with ALL. The risk-stratification is based on a novel, personalised algorithm using clinical characteristics, genetic changes in the leukaemia and response to therapy.
The protocol will, based on a personalised risk-approach, define a platform for diagnosis and treatment onto which randomized as well as non-randomised interventions and translational studies can be added. This platform can also be used by countries joining the collaboration at a later date to prepare for full participation.
High-risk B-lineage patients may be stratified to Chimeric Antigen Receptor T-cell (CAR-T) therapy as an alternative to high-risk blocks and stem-cell transplant to reduce the side-effects.
Translational and other therapy-related research will be promoted by the common master protocol.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
- 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.
- Age 0 - < 46 years (one day before 46th birthday) at the time of diagnosis, with the exception of infants with KMT2A-r BCP ALL (see exclusion criteria below).
- 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 (>10mg/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, see section 17.8.
- Female patients, who are breast-feeding.
- Essential data missing from the registration of characteristics at diagnosis (in consultation with the protocol chair).
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Participants with newly diagnosed ALL Observational -
- Primary Outcome Measures
Name Time Method Overall survival (OS) compared to historical controls 5 year Event-free survival (EFS) compared to historical controls 5 year
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (47)
Turku University Hospital, Dept of Paediatrics
🇫🇮Turku, Finland
Aalborg University Hospital, Dept of Paediatrics
🇩🇰Aalborg, Denmark
Landspitali University Hospital, Children's Hospital
🇮🇸Reykjavík, Iceland
Oslo University Hospital, Dept of Haematology
🇳🇴Oslo, Norway
Rigshospitalet, Dept of Paediatrics
🇩🇰Copenhagen, Denmark
Odense University Hospital, Dept of Paediatrics
🇩🇰Odense, Denmark
North Estonia Medical Centre, Dept of Haematology
🇪🇪Tallinn, Estonia
Tartu University Hospital
🇪🇪Tartu, Estonia
Tallinn Children´s Hospital, Dept of Paediatrics
🇪🇪Tallinn, Estonia
Helsinki University Hospital, Dept of Haematology
🇫🇮Helsinki, Finland
Kuopio University Hospital, Dept of Haematology
🇫🇮Kuopio, Finland
Tampere University Hospital, Dept of Paediatrics
🇫🇮Tampere, Finland
Children's Hospital, Affiliate of Vilnius University Hospital
🇱🇹Vilnius, Lithuania
Oslo University Hospital, Dept of paediatric haemato- and oncology
🇳🇴Oslo, Norway
University Hospital North Norway, Dept of Haematology
🇳🇴Tromsø, Norway
University Hospital of North Norway, Dept of Paediatrics
🇳🇴Tromsø, Norway
St. Olavs University Hospital, Dept of Paediatrics
🇳🇴Trondheim, Norway
Hospital Universitario San Joan de Déu
🇪🇸Barcelona, Spain
Aarhus University Hospital, Child and Adolescent Health
🇩🇰Aarhus, Denmark
Helsinki University Hospital, Dept of Paediatrics
🇫🇮Helsinki, Finland
Tampere University Hospital, Dept of Haematology
🇫🇮Tampere, Finland
Rigshospitalet, Dept of Haematology
🇩🇰Copenhagen, Denmark
Aarhus University Hospital
🇩🇰Aarhus, Denmark
Oulu University Hospital, Dept of Haematology, Dept of Medicine
🇫🇮Oulu, Finland
Turku University Hospital, Clinical Haematology and Stem Cell Transplantation Unit
🇫🇮Turku, Finland
Haukeland University Hospital, Dept of Paediatrics
🇳🇴Bergen, Norway
St. Olavs University Hospital, Dept of Haematology
🇳🇴Trondheim, Norway
Linköping University Hospital, Dept of Haematology
🇸🇪Linköping, Sweden
Linköping University Hospital, Dept of Paediatrics
🇸🇪Linköping, Sweden
Karolinska University Hospital, Dept of Paediatric Oncology and Haematology
🇸🇪Stockholm, Sweden
Norrland University Hospital, Dept of Haematology
🇸🇪Umeå, Sweden
Hospital Infantil Universitario Nino Jesus
🇪🇸Madrid, Spain
Kuopio University Hospital, Dept of Paediatrics
🇫🇮Kuopio, Finland
Oulu University Hospital, Dept of Paediatrics
🇫🇮Oulu, Finland
Vilnius University Hospital
🇱🇹Vilnius, Lithuania
Haukeland University Hospital, Dept of Haematology
🇳🇴Bergen, Norway
Skåne University Hospital, Dept of Paediatrics
🇸🇪Lund, Sweden
Norrland University Hospital, Dept of Paediatrics
🇸🇪Umeå, Sweden
Stavanger University Hospital, Dept of Haematology
🇳🇴Stavanger, Norway
Sahlgrenska University Hospital, Dept of Paediatric Haematology and Oncology
🇸🇪Gothenburg, Sweden
Karolinska University Hospital, Patient area Haematology
🇸🇪Stockholm, Sweden
Uppsala University Hospital, Dept of Haematology
🇸🇪Uppsala, Sweden
Örebro University Hospital, Section for Haematology
🇸🇪Örebro, Sweden
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Sahlgrenska University Hospital, Section for Haematology and coagulation
🇸🇪Gothenburg, Sweden
Skåne University Hospital, Dept of Haematology
🇸🇪Lund, Sweden
Uppsala University Hospital, Dept of Paediatric Haematology and Oncology
🇸🇪Uppsala, Sweden