NDLI: 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

Content Provider	Springer Nature : BioMed Central
Author	Toksvang, Linea Natalie Als-Nielsen, Bodil Bacon, Christopher Bertasiute, Ruta Duarte, Ximo Escherich, Gabriele Helgadottir, Elín Anna Johannsdottir, Inga Rinvoll Jónsson, Ólafur G. Kozlowski, Piotr Langenskjöld, Cecilia Lepik, Kristi Niinimäki, Riitta Overgaard, Ulrik Malthe Punab, Mari Räty, Riikka Segers, Heidi van der Sluis, Inge Smith, Owen Patrick Strullu, Marion Vaitkevičienė, Goda Wik, Hilde Skuterud Heyman, Mats Schmiegelow, Kjeld
Abstract	Background A critical challenge in current acute lymphoblastic leukemia (ALL) therapy is treatment intensification in order to reduce the relapse rate in the subset of patients at the highest risk of relapse. The year-long maintenance phase is essential in relapse prevention. The Thiopurine Enhanced ALL Maintenance (TEAM) trial investigates a novel strategy for ALL maintenance. Methods TEAM is a randomized phase 3 sub-protocol to the ALLTogether1 trial, which includes patients 0–45 years of age with newly diagnosed B-cell precursor or T-cell ALL, and stratified to the intermediate risk-high (IR-high) group, in 13 European countries. In the TEAM trial, the traditional methotrexate (MTX)/6-mercaptopurine (6MP) maintenance backbone (control arm) is supplemented with low dose (2.5–12.5 mg/m2/day) oral 6-thioguanine (6TG) (experimental arm), while the starting dose of 6MP is reduced from 75 to 50 mg/m2/day. A total of 778 patients will be included in TEAM during ~ 5 years. The study will close when the last included patient has been followed for 5 years from the end of induction therapy. The primary objective of the study is to significantly improve the disease-free survival (DFS) of IR-high ALL patients by adding 6TG to 6MP/MTX-based maintenance therapy. TEAM has 80% power to detect a 7% increase in 5-year DFS through a 50% reduction in relapse rate. DFS will be evaluated by intention-to-treat analysis. In addition to reducing relapse, TEAM may also reduce hepatotoxicity and hypoglycemia caused by high levels of methylated 6MP metabolites. Methotrexate/6MP metabolites will be monitored and low levels will be reported back to clinicians to identify potentially non-adherent patients. Discussion TEAM provides a novel strategy for maintenance therapy in ALL with the potential of improving DFS through reducing relapse rate. Potential risk factors that have been considered include hepatic sinusoidal obstruction syndrome/nodular regenerative hyperplasia, second cancer, infection, and osteonecrosis. Metabolite monitoring can potentially increase treatment adherence in both treatment arms. Trial registration EudraCT, 2018–001795-38. Registered 2020-05-15, Clinicaltrials.gov , NCT04307576 . Registered 2020-03-13, https://clinicaltrials.gov/ct2/show/NCT04307576
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-022-09522-3.pdf
Ending Page	19
Page Count	19
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-022-09522-3
Journal	BMC Cancer
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2022-05-02
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Acute lymphoblastic leukemia Maintenance Thiopurines 6-mercaptopurine Methotrexate 6-thioguanine DNA-TG Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Assessment of Thiopurine-based drugs according to Thiopurine S-methyltransferase genotype in patients with Acute Lymphoblastic Leukemia.

Assessment of Thiopurine-based drugs according to Thiopurine S-methyltransferase genotype in patients with Acute Lymphoblastic Leukemia.

Thiopurines for the Treatment of Acute Lymphoblastic Leukemia in Children: What’s Old Is New

Genetic Polymorphism of Thiopurine S-methyltransferase in Children with Acute Lymphoblastic Leukemia in Jordan

The impact of high-dose methotrexate on intracellular 6-mercaptopurine disposition during interval therapy of childhood acute lymphoblastic leukemia

Systemic Exposure to Thiopurines and Risk of Relapse in Children With Acute Lymphoblastic Leukemia: A Children’s Oncology Group Study

A Simplistic Individualization Method for 6-Mercaptopurine in Acute Lymphoblastic Leukemia Children

Optimal predictor for 6-mercaptopurine intolerance in Chinese children with acute lymphoblastic leukemia: NUDT15, TPMT, or ITPA genetic variants?

Myelotoxicity, Pharmacokinetics, and Relapse Rate with Methotrexate/6-Mercaptopurine Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia

Similar Documents

Assessment of Thiopurine-based drugs according to Thiopurine S-methyltransferase genotype in patients with Acute Lymphoblastic Leukemia.

Assessment of Thiopurine-based drugs according to Thiopurine S-methyltransferase genotype in patients with Acute Lymphoblastic Leukemia.

Thiopurines for the Treatment of Acute Lymphoblastic Leukemia in Children: What’s Old Is New

Genetic Polymorphism of Thiopurine S-methyltransferase in Children with Acute Lymphoblastic Leukemia in Jordan

The impact of high-dose methotrexate on intracellular 6-mercaptopurine disposition during interval therapy of childhood acute lymphoblastic leukemia

Systemic Exposure to Thiopurines and Risk of Relapse in Children With Acute Lymphoblastic Leukemia: A Children’s Oncology Group Study

A Simplistic Individualization Method for 6-Mercaptopurine in Acute Lymphoblastic Leukemia Children

Optimal predictor for 6-mercaptopurine intolerance in Chinese children with acute lymphoblastic leukemia: NUDT15, TPMT, or ITPA genetic variants?

Myelotoxicity, Pharmacokinetics, and Relapse Rate with Methotrexate/6-Mercaptopurine Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia