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

Leukemia, Acute Lymphoblastic Clinical Trial

Official title:

A Treatment Study Protocol of the ALLTogether Consortium for Infants, Children and Young Adults (0-45 Years of Age) With Newly Diagnosed Acute Lymphoblastic Leukaemia (ALL): a Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03911128
• Other study ID #: ALLTogether1 pilot
• Status: Recruiting
• Start date: August 29, 2019
• Est. completion date: August 2030

Study information

• Verified date: March 2024
• Source: Karolinska University Hospital
• Contact: Mats Heyman, M.D. PhD
• Phone: +46 8 517 704 07
• Email: mats.heyman[@]ki.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: August 2030
• Est. primary completion date: August 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 45 Years

Eligibility

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 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.

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). 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).

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Acute Lymphoblastic
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Other:
• Observational
Observational study - no intervention

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital, Dept of Paediatrics	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Aarhus University Hospital, Child and Adolescent Health	Aarhus
Denmark	Rigshospitalet, Dept of Haematology	Copenhagen
Denmark	Rigshospitalet, Dept of Paediatrics	Copenhagen
Denmark	Odense University Hospital, Dept of Paediatrics	Odense
Estonia	North Estonia Medical Centre, Dept of Haematology	Tallinn
Estonia	Tallinn Children´s Hospital, Dept of Paediatrics	Tallinn
Estonia	Tartu University Hospital	Tartu
Finland	Helsinki University Hospital, Dept of Haematology	Helsinki
Finland	Helsinki University Hospital, Dept of Paediatrics	Helsinki
Finland	Kuopio University Hospital, Dept of Haematology	Kuopio
Finland	Kuopio University Hospital, Dept of Paediatrics	Kuopio
Finland	Oulu University Hospital, Dept of Haematology, Dept of Medicine	Oulu
Finland	Oulu University Hospital, Dept of Paediatrics	Oulu
Finland	Tampere University Hospital, Dept of Haematology	Tampere
Finland	Tampere University Hospital, Dept of Paediatrics	Tampere
Finland	Turku University Hospital, Clinical Haematology and Stem Cell Transplantation Unit	Turku
Finland	Turku University Hospital, Dept of Paediatrics	Turku
Iceland	Landspitali University Hospital, Children's Hospital	Reykjavík
Lithuania	Children's Hospital, Affiliate of Vilnius University Hospital	Vilnius
Lithuania	Vilnius University Hospital	Vilnius
Norway	Haukeland University Hospital, Dept of Haematology	Bergen
Norway	Haukeland University Hospital, Dept of Paediatrics	Bergen
Norway	Oslo University Hospital, Dept of Haematology	Oslo
Norway	Oslo University Hospital, Dept of paediatric haemato- and oncology	Oslo
Norway	Stavanger University Hospital, Dept of Haematology	Stavanger
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 Haematology	Trondheim
Norway	St. Olavs University Hospital, Dept of Paediatrics	Trondheim
Spain	Hospital Universitario San Joan de Déu	Barcelona
Spain	Hospital Infantil Universitario Nino Jesus	Madrid
Sweden	Sahlgrenska University Hospital, Dept of Paediatric Haematology and Oncology	Gothenburg
Sweden	Sahlgrenska University Hospital, Section for Haematology and coagulation	Gothenburg
Sweden	Linköping University Hospital, Dept of Haematology	Linköping
Sweden	Linköping University Hospital, Dept of Paediatrics	Linköping
Sweden	Skåne University Hospital, Dept of Haematology	Lund
Sweden	Skåne University Hospital, Dept of Paediatrics	Lund
Sweden	Örebro University Hospital, Section for Haematology	Örebro
Sweden	Karolinska University Hospital, Dept of Paediatric Oncology and Haematology	Stockholm
Sweden	Karolinska University Hospital, Patient area Haematology	Stockholm
Sweden	Norrland University Hospital, Dept of Haematology	Umeå
Sweden	Norrland University Hospital, Dept of Paediatrics	Umeå
Sweden	Uppsala University Hospital, Dept of Haematology	Uppsala
Sweden	Uppsala University Hospital, Dept of Paediatric Haematology and Oncology	Uppsala

Sponsors (4)

Lead Sponsor	Collaborator
Mats Heyman	NordForsk, Nordic Society for Pediatric Hematology and Oncology, The Swedish Childhood Cancer Foundation

Countries where clinical trial is conducted

Denmark,  Estonia,  Finland,  Iceland,  Lithuania,  Norway,  Spain,  Sweden, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival (EFS) compared to historical controls		5 year
Primary	Overall survival (OS) compared to historical controls		5 year