drugset / Trial / NCT05681260
Capizzi Escalating Methotrexate Versus High Dose Methotrexate in Children With Newly Diagnosed T-cell Lymphoblastic Lymphoma (T-LBL)
Phase 3
Recruiting
200 enrolled
Children's Cancer Group, China
Beijing Children's Hospital · collabCancer Hospital of Henan Province · collabCancer hospital of Shandong Province · collabChildren's Hospital of Hebei Province · collabChildren's Hospital of Scow University · collabNanjing Children's Hospital · collabQilu Children's Hospital · collabQilu Hospital of Shandong University · collabRuijin Hospital · collabShanghai Children's Hospital · collabShanghai Children's Medical Center · collabShenzhen Children's Hospital · collabSun Yat-Sen Memorial Hospital of Sun Yat-Sen University · collabThe Children's Hospital of Zhejiang University School of Medicine · collabThe First Affiliated Hospital of Zhengzhou University · collabThe Second Hospital of Anhui Medical University · collabTianjin Medical University Cancer Institute and Hospital · collabTongji Hospital · collabWest China Second University Hospital · collabWuhan Children's Hospital · collabXiangya Hospital of Central South University · collab
RandomizedParallel-groupOpen-labelTreatment
Summary
T-cell lymphoblastic lymphoma (T-LBL) is the second most common subtype of non-Hodgkin lymphoma (NHL) in children and adolescents. With current treatment, event-free survival (EFS) rates vary between 75%\~85%. Two different MTX intensification strategies are used commonly: HD-MTX with leucovorin rescue, and Capizzi-style MTX without leucovorin rescue plus PEG-ASP (C-MTX). Although superior outcome of patients with T-ALL receiving C-MTX compared with HD-MTX on the AALL0434 trial, the 2 approaches had not been compared directly in patients with T-LBL. There remains controversy on PET/CT interpretation in children with NHL. Large prospective studies in pediatric patients with T-LBL regarding PET/CT value for this is scarce. Around 1% pediatric patients with T-LBL will not achieve remission at the end of Induction (induction failure). The optimal treatment for this small subgroup is largely unclear. The BFM HR Blocks usually are applied to these patients even though the efficacy is unknown. Novel targeted therapies are needed for use. Dasatinib is identified as a targeted therapy for T-cell ALL in preclinical drug screening.
Timeline
- Start
- 2023-02-06
- Primary completion
- 2026-12-31
- Completion
- 2029-12-31
Publications
- Results Burkhardt B, Reiter A, Landmann E, Lang P, Lassay L, Dickerhoff R, Lakomek M, Henze G, von Stackelberg A. Poor outcome for children and adolescents with progressive disease or relapse of lymphoblastic lymphoma: a report from the berlin-frankfurt-muenster group. J Clin Oncol. 2009 Jul 10;27(20):3363-9. doi: 10.1200/JCO.2008.19.3367. Epub 2009 May 11.
- Results Burkhardt B, Woessmann W, Zimmermann M, Kontny U, Vormoor J, Doerffel W, Mann G, Henze G, Niggli F, Ludwig WD, Janssen D, Riehm H, Schrappe M, Reiter A. Impact of cranial radiotherapy on central nervous system prophylaxis in children and adolescents with central nervous system-negative stage III or IV lymphoblastic lymphoma. J Clin Oncol. 2006 Jan 20;24(3):491-9. doi: 10.1200/JCO.2005.02.2707.
- Results Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved Survival for Children and Young Adults With T-Lineage Acute Lymphoblastic Leukemia: Results From the Children's Oncology Group AALL0434 Methotrexate Randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. doi: 10.1200/JCO.2018.77.7250. Epub 2018 Aug 23.
- Results Asselin BL, Devidas M, Wang C, Pullen J, Borowitz MJ, Hutchison R, Lipshultz SE, Camitta BM. Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: a randomized study by the Children's Oncology Group (POG 9404). Blood. 2011 Jul 28;118(4):874-83. doi: 10.1182/blood-2010-06-292615. Epub 2011 Apr 7.
- Results Termuhlen AM, Smith LM, Perkins SL, Lones M, Finlay JL, Weinstein H, Gross TG, Abromowitch M. Disseminated lymphoblastic lymphoma in children and adolescents: results of the COG A5971 trial: a report from the Children's Oncology Group. Br J Haematol. 2013 Sep;162(6):792-801. doi: 10.1111/bjh.12460. Epub 2013 Jul 24.
- Results Coustan-Smith E, Sandlund JT, Perkins SL, Chen H, Chang M, Abromowitch M, Campana D. Minimal disseminated disease in childhood T-cell lymphoblastic lymphoma: a report from the children's oncology group. J Clin Oncol. 2009 Jul 20;27(21):3533-9. doi: 10.1200/JCO.2008.21.1318. Epub 2009 Jun 22.
- Results Hayashi RJ, Winter SS, Dunsmore KP, Devidas M, Chen Z, Wood BL, Hermiston ML, Teachey DT, Perkins SL, Miles RR, Raetz EA, Loh ML, Winick NJ, Carroll WL, Hunger SP, Lim MS, Gross TG, Bollard CM. Successful Outcomes of Newly Diagnosed T Lymphoblastic Lymphoma: Results From Children's Oncology Group AALL0434. J Clin Oncol. 2020 Sep 10;38(26):3062-3070. doi: 10.1200/JCO.20.00531. Epub 2020 Jun 17.
- Results Horton TM, Whitlock JA, Lu X, O'Brien MM, Borowitz MJ, Devidas M, Raetz EA, Brown PA, Carroll WL, Hunger SP. Bortezomib reinduction chemotherapy in high-risk ALL in first relapse: a report from the Children's Oncology Group. Br J Haematol. 2019 Jul;186(2):274-285. doi: 10.1111/bjh.15919. Epub 2019 Apr 7.
- Results Teachey DT, Devidas M, Wood BL, Chen Z, Hayashi RJ, Hermiston ML, Annett RD, Archer JH, Asselin BL, August KJ, Cho SY, Dunsmore KP, Fisher BT, Freedman JL, Galardy PJ, Harker-Murray P, Horton TM, Jaju AI, Lam A, Messinger YH, Miles RR, Okada M, Patel SI, Schafer ES, Schechter T, Singh N, Steele AC, Sulis ML, Vargas SL, Winter SS, Wood C, Zweidler-McKay P, Bollard CM, Loh ML, Hunger SP, Raetz EA. Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma. J Clin Oncol. 2022 Jul 1;40(19):2106-2118. doi: 10.1200/JCO.21.02678. Epub 2022 Mar 10.
- Results Rosolen A, Perkins SL, Pinkerton CR, Guillerman RP, Sandlund JT, Patte C, Reiter A, Cairo MS. Revised International Pediatric Non-Hodgkin Lymphoma Staging System. J Clin Oncol. 2015 Jun 20;33(18):2112-8. doi: 10.1200/JCO.2014.59.7203. Epub 2015 May 4.
- Results Sandlund JT, Guillerman RP, Perkins SL, Pinkerton CR, Rosolen A, Patte C, Reiter A, Cairo MS. International Pediatric Non-Hodgkin Lymphoma Response Criteria. J Clin Oncol. 2015 Jun 20;33(18):2106-11. doi: 10.1200/JCO.2014.59.0745. Epub 2015 May 4.
- Results Bhojwani D, McCarville MB, Choi JK, Sawyer J, Metzger ML, Inaba H, Davidoff AM, Gold R, Shulkin BL, Sandlund JT. The role of FDG-PET/CT in the evaluation of residual disease in paediatric non-Hodgkin lymphoma. Br J Haematol. 2015 Mar;168(6):845-53. doi: 10.1111/bjh.13219. Epub 2014 Nov 10.
- Results Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
- Results Teachey DT, O'Connor D. How I treat newly diagnosed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma in children. Blood. 2020 Jan 16;135(3):159-166. doi: 10.1182/blood.2019001557.
- Results Khanam T, Sandmann S, Seggewiss J, Ruether C, Zimmermann M, Norvil AB, Bartenhagen C, Randau G, Mueller S, Herbrueggen H, Hoffmann P, Herms S, Wei L, Woeste M, Wuensch C, Gowher H, Oschlies I, Klapper W, Woessmann W, Dugas M, Burkhardt B. Integrative genomic analysis of pediatric T-cell lymphoblastic lymphoma reveals candidates of clinical significance. Blood. 2021 Apr 29;137(17):2347-2359. doi: 10.1182/blood.2020005381.
- Results Laukkanen S, Gronroos T, Polonen P, Kuusanmaki H, Mehtonen J, Cloos J, Ossenkoppele G, Gjertsen B, Oystein B, Heckman C, Heinaniemi M, Kontro M, Lohi O. In silico and preclinical drug screening identifies dasatinib as a targeted therapy for T-ALL. Blood Cancer J. 2017 Sep 8;7(9):e604. doi: 10.1038/bcj.2017.87. No abstract available.
- Results Steinherz PG. CNS leukemia: problem of diagnosis, treatment, and outcome. J Clin Oncol. 1995 Feb;13(2):310-3. doi: 10.1200/JCO.1995.13.2.310. No abstract available.
- Results Salzburg J, Burkhardt B, Zimmermann M, Wachowski O, Woessmann W, Oschlies I, Klapper W, Wacker HH, Ludwig WD, Niggli F, Mann G, Gadner H, Riehm H, Schrappe M, Reiter A. Prevalence, clinical pattern, and outcome of CNS involvement in childhood and adolescent non-Hodgkin's lymphoma differ by non-Hodgkin's lymphoma subtype: a Berlin-Frankfurt-Munster Group Report. J Clin Oncol. 2007 Sep 1;25(25):3915-22. doi: 10.1200/JCO.2007.11.0700.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Methotrexate | Small molecule | — | — |
| Background | Bortezomib | Small molecule | — | — |
| Background | Cyclophosphamide | Other / unclassified | — | — |
| Background | Cytarabine | Small molecule | — | — |
| Background | Daunorubicin | Small molecule | — | — |
| Background | Dexamethasone | Small molecule | — | — |
| Background | Doxorubicin | Other / unclassified | — | — |
| Background | Etoposide | Small molecule | — | — |
| Background | Ifosfamide | Small molecule | — | — |
| Background | MERCAPTOPURINE ANHYDROUS | Small molecule | — | — |
| Background | Pegylated asparaginase | Unknown | — | — |
| Background | Prednisone | Other / unclassified | — | — |
| Background | Vincristine | Small molecule | — | — |
| Background | Vindesine | Small molecule | — | — |