International Study for Treatment of Childhood Relapsed Precursor B-Cell ALL 2020 (IntReALL BCP 2020)

Summary

The IntReALL BCP 2020 study aims to review recent developments and findings regarding chemoimmunotherapy with inotuzumab and immunotherapy with blinatumomab and to increase the use of promising new immunotherapeutic drugs as replacements for toxic SOC chemotherapy elements. The IntReALL BCP 2020 study has the potential to improve CR and EFS rates for all SR and HR groups, as well as for patients with IEM recurrence, by replacing toxic chemotherapy with targeted, less toxic immunotherapy strategies, and could establish these new approaches as SOC for children with relapsed BCP ALL in the future.

Timeline

Start

2026-04-01

Primary completion

2033-03-31

Completion

2033-03-31

Publications

• Background Eckert C, Parker C, Moorman AV, Irving JA, Kirschner-Schwabe R, Groeneveld-Krentz S, Revesz T, Hoogerbrugge P, Hancock J, Sutton R, Henze G, Chen-Santel C, Attarbaschi A, Bourquin JP, Sramkova L, Zimmermann M, Krishnan S, von Stackelberg A, Saha V. Risk factors and outcomes in children with high-risk B-cell precursor and T-cell relapsed acute lymphoblastic leukaemia: combined analysis of ALLR3 and ALL-REZ BFM 2002 clinical trials. Eur J Cancer. 2021 Jul;151:175-189. doi: 10.1016/j.ejca.2021.03.034. Epub 2021 May 16.
• Background Hagedorn N, Acquaviva C, Fronkova E, von Stackelberg A, Barth A, zur Stadt U, Schrauder A, Trka J, Gaspar N, Seeger K, Henze G, Cave H, Eckert C; Resistant Disease Committee of the International BFM study group. Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia: a more precise definition of "isolated" and its possible clinical implications, a collaborative study of the Resistant Disease Committee of the International BFM study group. Blood. 2007 Dec 1;110(12):4022-9. doi: 10.1182/blood-2007-04-082040. Epub 2007 Aug 24.
• Background Eckert C, Henze G, Seeger K, Hagedorn N, Mann G, Panzer-Grumayer R, Peters C, Klingebiel T, Borkhardt A, Schrappe M, Schrauder A, Escherich G, Sramkova L, Niggli F, Hitzler J, von Stackelberg A. Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group. J Clin Oncol. 2013 Jul 20;31(21):2736-42. doi: 10.1200/JCO.2012.48.5680. Epub 2013 Jun 17.
• Background Bader P, Kreyenberg H, von Stackelberg A, Eckert C, Salzmann-Manrique E, Meisel R, Poetschger U, Stachel D, Schrappe M, Alten J, Schrauder A, Schulz A, Lang P, Muller I, Albert MH, Willasch AM, Klingebiel TE, Peters C. Monitoring of minimal residual disease after allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia allows for the identification of impending relapse: results of the ALL-BFM-SCT 2003 trial. J Clin Oncol. 2015 Apr 10;33(11):1275-84. doi: 10.1200/JCO.2014.58.4631. Epub 2015 Jan 20.
• Background Lissat A, van Schewick C, Steffen IG, Arakawa A, Bourquin JP, Burkhardt B, Henze G, Mann G, Peters C, Sramkova L, Eckert C, von Stackelberg A, Chen-Santel C. Other (Non-CNS/Testicular) Extramedullary Localizations of Childhood Relapsed Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma-A Report from the ALL-REZ Study Group. J Clin Med. 2021 Nov 14;10(22):5292. doi: 10.3390/jcm10225292.
• Background Buchmann S, Schrappe M, Baruchel A, Biondi A, Borowitz M, Campbell M, Cario G, Cazzaniga G, Escherich G, Harrison CJ, Heyman M, Hunger SP, Kiss C, Liu HC, Locatelli F, Loh ML, Manabe A, Mann G, Pieters R, Pui CH, Rives S, Schmiegelow K, Silverman LB, Stary J, Vora A, Brown P. Remission, treatment failure, and relapse in pediatric ALL: an international consensus of the Ponte-di-Legno Consortium. Blood. 2022 Mar 24;139(12):1785-1793. doi: 10.1182/blood.2021012328.
• Background von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, Bader P, O'Brien MM, Brethon B, Bhojwani D, Schlegel PG, Borkhardt A, Rheingold SR, Cooper TM, Zwaan CM, Barnette P, Messina C, Michel G, DuBois SG, Hu K, Zhu M, Whitlock JA, Gore L. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2016 Dec 20;34(36):4381-4389. doi: 10.1200/JCO.2016.67.3301. Epub 2016 Oct 31.
• Background Brivio E, Locatelli F, Lopez-Yurda M, Malone A, Diaz-de-Heredia C, Bielorai B, Rossig C, van der Velden VHJ, Ammerlaan ACJ, Thano A, van der Sluis IM, den Boer ML, Chen Y, Sleight B, Brethon B, Nysom K, Sramkova L, Ora I, Vinti L, Chen-Santel C, Zwaan CM. A phase 1 study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC-059 study). Blood. 2021 Mar 25;137(12):1582-1590. doi: 10.1182/blood.2020007848.
• Background Wu JH, Pennesi E, Bautista F, Garrett M, Fukuhara K, Brivio E, Ammerlaan ACJ, Locatelli F, van der Sluis IM, Rossig C, Chen-Santel C, Bielorai B, Petit A, Stary J, Diaz-de-Heredia C, Rives S, O'Marcaigh A, Rizzari C, Engstler G, Nysom K, Rubio-San-Simon A, Bruno B, Bertrand Y, Brethon B, Rialland F, Plat G, Dirksen U, Sramkova L, Zwaan CM, Huitema ADR. Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059. Clin Pharmacokinet. 2024 Jul;63(7):981-997. doi: 10.1007/s40262-024-01386-z. Epub 2024 Jun 22.
• Background Stock W, Martinelli G, Stelljes M, DeAngelo DJ, Gokbuget N, Advani AS, O'Brien S, Liedtke M, Merchant AA, Cassaday RD, Wang T, Zhang H, Vandendries E, Jabbour E, Marks DI, Kantarjian HM. Efficacy of inotuzumab ozogamicin in patients with Philadelphia chromosome-positive relapsed/refractory acute lymphoblastic leukemia. Cancer. 2021 Mar 15;127(6):905-913. doi: 10.1002/cncr.33321. Epub 2020 Nov 24.
• Background Pennesi E, Michels N, Brivio E, van der Velden VHJ, Jiang Y, Thano A, Ammerlaan AJC, Boer JM, Beverloo HB, Sleight B, Chen Y, Vormoor-Burger B, Rives S, Bielorai B, Rossig C, Petit A, Rizzari C, Engstler G, Stary J, Bautista Sirvent FJ, Chen-Santel C, Bruno B, Bertrand Y, Rialland F, Plat G, Reinhardt D, Vinti L, Von Stackelberg A, Locatelli F, Zwaan CM. Inotuzumab ozogamicin as single agent in pediatric patients with relapsed and refractory acute lymphoblastic leukemia: results from a phase II trial. Leukemia. 2022 Jun;36(6):1516-1524. doi: 10.1038/s41375-022-01576-3. Epub 2022 Apr 25.
• Background Rabik CA, Wang S, Chadda R, Przepiorka D, Vallejo J, Jiang X, Theoret MR, de Claro RA. FDA Approval Summary: Blinatumomab for the Treatment of B-Cell Precursor Acute Lymphoblastic Leukemia in the Consolidation Phase of Multiphase Chemotherapy. Clin Cancer Res. 2025 Oct 15;31(20):4230-4238. doi: 10.1158/1078-0432.CCR-25-1034.
• Background Mejstrikova E, Klinger M, Markovic A, Zugmaier G, Locatelli F. CD19 expression in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia pre- and post-treatment with blinatumomab. Pediatr Blood Cancer. 2021 Dec;68(12):e29323. doi: 10.1002/pbc.29323. Epub 2021 Sep 14.
• Background Locatelli F, Zugmaier G, Rizzari C, Morris JD, Gruhn B, Klingebiel T, Parasole R, Linderkamp C, Flotho C, Petit A, Micalizzi C, Mergen N, Mohammad A, Kormany WN, Eckert C, Moricke A, Sartor M, Hrusak O, Peters C, Saha V, Vinti L, von Stackelberg A. Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):843-854. doi: 10.1001/jama.2021.0987.
• Background Kantarjian H, Haddad FG, Jain N, Sasaki K, Short NJ, Loghavi S, Kanagal-Shamanna R, Jorgensen J, Khouri I, Kebriaei P, Alvarado Y, Kadia T, Paul S, Garcia-Manero G, Dabaja B, Yilmaz M, Jacob J, Garris R, O'Brien S, Ravandi F, Jabbour E. Results of salvage therapy with mini-hyper-CVD and inotuzumab ozogamicin with or without blinatumomab in pre-B acute lymphoblastic leukemia. J Hematol Oncol. 2023 May 2;16(1):44. doi: 10.1186/s13045-023-01444-2.
• Background Jabbour E, Short NJ, Jain N, Huang X, Montalban-Bravo G, Banerjee P, Rezvani K, Jiang X, Kim KH, Kanagal-Shamanna R, Khoury JD, Patel K, Kadia TM, Daver N, Chien K, Alvarado Y, Garcia-Manero G, Issa GC, Haddad FG, Kwari M, Thankachan J, Delumpa R, Macaron W, Garris R, Konopleva M, Ravandi F, Kantarjian H. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2023 Jan;10(1):e24-e34. doi: 10.1016/S2352-3026(22)00319-2. Epub 2022 Nov 16.
• Background Foa R, Bassan R, Elia L, Piciocchi A, Soddu S, Messina M, Ferrara F, Lunghi M, Mule A, Bonifacio M, Fracchiolla N, Salutari P, Fazi P, Guarini A, Rambaldi A, Chiaretti S. Long-Term Results of the Dasatinib-Blinatumomab Protocol for Adult Philadelphia-Positive ALL. J Clin Oncol. 2024 Mar 10;42(8):881-885. doi: 10.1200/JCO.23.01075. Epub 2023 Dec 21.
• Background Brown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowitz MJ, Raetz EA, Zugmaier G, Sharon E, Bernhardt MB, Terezakis SA, Gore L, Whitlock JA, Pulsipher MA, Hunger SP, Loh ML. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):833-842. doi: 10.1001/jama.2021.0669.

Drugs

Indications