{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:53:23Z","timestamp":1781643203665,"version":"3.54.5"},"reference-count":11,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,7,7]],"date-time":"2011-07-07T00:00:00Z","timestamp":1309996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Novel agents are needed for patients with refractory and relapsed acute lymphoblastic leukaemia (ALL). Combotox is a 1:1 mixture of two immunotoxins (ITs), prepared by coupling deglycosylated ricin A chain (dgRTA) to monoclonal antibodies directed against CD22 (RFB4\u2010dgRTA) and CD19 (HD37\u2010dgRTA). Pre\u2010clinical data demonstrated that Combotox was effective in killing both pre\u2010B\u2010ALL cell lines and cells from patients with pre\u2010B ALL. A clinical study of paediatric patients in which 3 of 17 patients with ALL experienced complete remission, supported the preclinical work and motivated this study. This study was a Phase I, dose\u2010escalation trial using Combotox in adults with refractory or relapsed B\u2010lineage\u2010ALL. A cycle consisted of three doses, with one dose given every other day. Dose levels were 3, 5, 6, 7 and 8\u2003mg\/m<jats:sup>2<\/jats:sup> per dose. Seventeen patients, aged 19\u201372\u2003years, were enrolled in this multi\u2010institution study. The maximum tolerated dose was 7\u2003mg\/m<jats:sup>2<\/jats:sup>\/dose (21\u2003mg\/m<jats:sup>2<\/jats:sup>\/cycle) and vascular leak syndrome was the dose\u2010limiting toxicity. Two patients developed reversible grade 3 elevations in liver function tests. One patient achieved partial remission and proceeded to allogeneic stem cell transplantation. All patients with peripheral blasts experienced decreased blast counts following the administration of Combotox. Thus, Combotox can be safely administered to adults with refractory leukaemia.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2011.08762.x","type":"journal-article","created":{"date-parts":[[2011,7,7]],"date-time":"2011-07-07T08:15:26Z","timestamp":1310026526000},"page":"471-476","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["A phase I study of a combination of anti\u2010CD19 and anti\u2010CD22 immunotoxins (Combotox) in adult patients with refractory B\u2010lineage acute lymphoblastic leukaemia"],"prefix":"10.1111","volume":"154","author":[{"given":"John","family":"Schindler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srikanth","family":"Gajavelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Ravandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YuMin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Parekh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Braunchweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Barta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Ghetie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Vitetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,7,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.9.2624.2624"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.4049\/jimmunol.134.3.1524","article-title":"Human B cell development. 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