EsPhALL2017/COGAALL1631

Approximately 3-5% of cases of ALL in children and adolescents are characterised by the presence of the Philadelphia chromosome (translocation t(9;22), molecular equivalent: BCR-ABL fusion). While historically the prognosis of affected children treated with conventional chemotherapy, supplemented if possible by allogeneic haematopoietic stem cell transplantation (HSCT), was extremely poor with cure rates of less than 50%, the systematic introduction of the tyrosine kinase inhibitor (TKI) imatinib, which was tested in a large European (EsPhALL) and several U.S. multicentre studies (COG), has led to the fact that more than half of patients can now be cured even without HSCT. However, the chemotherapy chosen in both consortia was highly intensive and accordingly associated with the occurrence of severe therapy toxicity including life-threatening infections; the use of high cumulative doses of anthracyclines and high-dose cytarabine as well as ifosfamide and etoposide also entails a high risk of severe long-term consequences. A reduction in these undesirable side effects while maintaining an acceptably low recurrence rate would represent a relevant advance in the treatment of affected children and adolescents.

{ "short_title": "EsPhALL2017/COGAALL1631", "data_mode": "900", "data_mode_number": "000002453", "official_title": "International phase 3 trial in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) testing imatinib in combination with two different cytotoxic chemotherapy backbones - Internationale Phase-3 Studie f\u00fcr Philadelphia-Chromosom-positive Akute lymphoblastische Leuk\u00e4mie", "accrual_state": "running", "therapeutic_value": "therapeutic", "therapieansatz_value": "kurativ", "therapieintervention_value": null, "therapielinie_value": "first", "ctgov_number": null, "eudract_number": "2017-000705-20", "general_contact_email": "Kik-dokuteam-hs65@ukdd.de", "general_contact_phone": "+49 351-4585035", "hauptpruefer_dd_name": "Tobias D\u00e4britz", "description_laie_de": "Ca. 3-5 % der F\u00e4lle mit ALL im Kindes- und Jugendalter sind durch das Vorhandensein des Philadelphia-Chromosoms (Translokation t(9;22), molekulares \u00c4quivalent: BCR-ABL-Fusion) charakterisiert. W\u00e4hrend historisch die Prognose der betroffenen Kinder bei Behandlung mit konventioneller Chemotherapie, erg\u00e4nzt wenn m\u00f6glich durch allogene h\u00e4matopoetische Stammzelltransplantation (HSZT) mit Heilungsraten von unter 50% ausgesprochen schlecht war, f\u00fchrte die systematische Einf\u00fchrung des Tyrosinkinase-Inhibitors (TKI) Imatinib, die im Rahmen einer gro\u00dfen europ\u00e4ischen (EsPhALL) und mehreren U.S. amerikanischen multizentrischen Studien (COG) gepr\u00fcft wurde, dazu, dass mittlerweile mehr als die H\u00e4lfte der Patienten selbst ohne HSZT geheilt werden kann. Die in beiden Konsortien gew\u00e4hlte Chemotherapie war jedoch hochintensiv und entsprechend mit den Auftreten von schwerer Therapietoxizit\u00e4t einschlie\u00dflich lebensbedrohlichen Infektionen verbunden; der Einsatz von hohen kumulativen Dosen von Anthrazyklinen und Hochdosis-Cytarabin sowie von Ifosfamid und Etoposid bringt zudem ein hohes Risiko schwerer Langzeitfolgen mit sich. Eine Reduktion dieser unerw\u00fcnschten Nebenwirkungen bei gleichzeitigem Erhalt einer akzeptabel niedrigen Rezidivrate w\u00fcrde einen relevanten Fortschritt in der Behandlung der betroffenen Kinder und Jugendlichen bedeuten.", "description_laie_en": null, "description_expert_de": null, "description_expert_en": "Approximately 3-5% of cases of ALL in children and adolescents are characterised by the presence of the Philadelphia chromosome (translocation t(9;22), molecular equivalent: BCR-ABL fusion). While historically the prognosis of affected children treated with conventional chemotherapy, supplemented if possible by allogeneic haematopoietic stem cell transplantation (HSCT), was extremely poor with cure rates of less than 50%, the systematic introduction of the tyrosine kinase inhibitor (TKI) imatinib, which was tested in a large European (EsPhALL) and several U.S. multicentre studies (COG), has led to the fact that more than half of patients can now be cured even without HSCT. However, the chemotherapy chosen in both consortia was highly intensive and accordingly associated with the occurrence of severe therapy toxicity including life-threatening infections; the use of high cumulative doses of anthracyclines and high-dose cytarabine as well as ifosfamide and etoposide also entails a high risk of severe long-term consequences. A reduction in these undesirable side effects while maintaining an acceptably low recurrence rate would represent a relevant advance in the treatment of affected children and adolescents.", "rechtsgrundlage_value": "AMG", "phase_amg_value": null, "main_cat_id": 14, "sub_cat_id": 66 }

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