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Thiopurine Enhanced ALL Maintenance (TEAM)

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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. / 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.

In: BMC CANCER, Vol. 22, No. 1, 483, 02.05.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Toksvang, LN, Als-Nielsen, B, Bacon, C, Bertasiute, R, Duarte, X, Escherich, G, Helgadottir, EA, Johannsdottir, IR, Jónsson, ÓG, Kozlowski, P, Langenskjöld, C, Lepik, K, Niinimäki, R, Overgaard, UM, Punab, M, Räty, R, Segers, H, van der Sluis, I, Smith, OP, Strullu, M, Vaitkevičienė, G, Wik, HS, Heyman, M & Schmiegelow, K 2022, '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', BMC CANCER, vol. 22, no. 1, 483. https://doi.org/10.1186/s12885-022-09522-3

APA

Toksvang, L. N., Als-Nielsen, B., Bacon, C., Bertasiute, R., Duarte, X., Escherich, G., Helgadottir, E. A., Johannsdottir, I. R., Jónsson, Ó. G., Kozlowski, P., Langenskjöld, C., Lepik, K., Niinimäki, R., Overgaard, U. M., Punab, M., Räty, R., Segers, H., van der Sluis, I., Smith, O. P., ... Schmiegelow, K. (2022). 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. BMC CANCER, 22(1), [483]. https://doi.org/10.1186/s12885-022-09522-3

Vancouver

Toksvang LN, Als-Nielsen B, Bacon C, Bertasiute R, Duarte X, Escherich G et al. 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. BMC CANCER. 2022 May 2;22(1). 483. https://doi.org/10.1186/s12885-022-09522-3

Bibtex

@article{cb67aceba61f45cda1a3761805f86d2a,
title = "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",
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.",
keywords = "Adolescent, Adult, Child, Child, Preschool, Disease-Free Survival, Humans, Infant, Infant, Newborn, Mercaptopurine, Methotrexate, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy, Randomized Controlled Trials as Topic, Recurrence, Risk Factors, T-Lymphocytes, Thioguanine/therapeutic use, Young Adult",
author = "Toksvang, {Linea Natalie} and Bodil Als-Nielsen and Christopher Bacon and Ruta Bertasiute and Ximo Duarte and Gabriele Escherich and Helgadottir, {El{\'i}n Anna} and Johannsdottir, {Inga Rinvoll} and J{\'o}nsson, {{\'O}lafur G} and Piotr Kozlowski and Cecilia Langenskj{\"o}ld and Kristi Lepik and Riitta Niinim{\"a}ki and Overgaard, {Ulrik Malthe} and Mari Punab and Riikka R{\"a}ty and Heidi Segers and {van der Sluis}, Inge and Smith, {Owen Patrick} and Marion Strullu and Goda Vaitkevi{\v c}ienė and Wik, {Hilde Skuterud} and Mats Heyman and Kjeld Schmiegelow",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
month = may,
day = "2",
doi = "10.1186/s12885-022-09522-3",
language = "English",
volume = "22",
journal = "BMC CANCER",
issn = "1471-2407",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Thiopurine Enhanced ALL Maintenance (TEAM)

T2 - 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

AU - Toksvang, Linea Natalie

AU - Als-Nielsen, Bodil

AU - Bacon, Christopher

AU - Bertasiute, Ruta

AU - Duarte, Ximo

AU - Escherich, Gabriele

AU - Helgadottir, Elín Anna

AU - Johannsdottir, Inga Rinvoll

AU - Jónsson, Ólafur G

AU - Kozlowski, Piotr

AU - Langenskjöld, Cecilia

AU - Lepik, Kristi

AU - Niinimäki, Riitta

AU - Overgaard, Ulrik Malthe

AU - Punab, Mari

AU - Räty, Riikka

AU - Segers, Heidi

AU - van der Sluis, Inge

AU - Smith, Owen Patrick

AU - Strullu, Marion

AU - Vaitkevičienė, Goda

AU - Wik, Hilde Skuterud

AU - Heyman, Mats

AU - Schmiegelow, Kjeld

N1 - © 2022. The Author(s).

PY - 2022/5/2

Y1 - 2022/5/2

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Child

KW - Child, Preschool

KW - Disease-Free Survival

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Mercaptopurine

KW - Methotrexate

KW - Middle Aged

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy

KW - Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy

KW - Randomized Controlled Trials as Topic

KW - Recurrence

KW - Risk Factors

KW - T-Lymphocytes

KW - Thioguanine/therapeutic use

KW - Young Adult

U2 - 10.1186/s12885-022-09522-3

DO - 10.1186/s12885-022-09522-3

M3 - SCORING: Journal article

C2 - 35501736

VL - 22

JO - BMC CANCER

JF - BMC CANCER

SN - 1471-2407

IS - 1

M1 - 483

ER -