title: A phase I study of a combination of anti-CD19 and anti-CD22 immunotoxins (Combotox) in adult patients with refractory B-lineage acute lymphoblastic leukaemia.
abstract: 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-dgRTA) and CD19 (HD37-dgRTA). Pre-clinical data demonstrated that Combotox was effective in killing both pre-B-ALL cell lines and cells from patients with pre-B 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-escalation trial using Combotox in adults with refractory or relapsed B-lineage-ALL. A cycle consisted of three doses, with one dose given every other day. Dose levels were 3, 5, 6, 7 and 8 mg/m(2) per dose. Seventeen patients, aged 19-72 years, were enrolled in this multi-institution study. The maximum tolerated dose was 7 mg/m(2) /dose (21 mg/m(2) /cycle) and vascular leak syndrome was the dose-limiting 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.
authors: Cancer Immunobiology Center, University of Texas, Southwestern Medical Center, Dallas, TX 75390-8576, USA. john.schindler@utsouthwestern.edu
authors: John
authors: J
authors: Schindler
authors: Srikanth
authors: S
authors: Gajavelli
authors: Farhad
authors: F
authors: Ravandi
authors: Yumin
authors: Y
authors: Shen
authors: Samir
authors: S
authors: Parekh
authors: Ira
authors: I
authors: Braunchweig
authors: Stefan
authors: S
authors: Barta
authors: Victor
authors: V
authors: Ghetie
authors: Ellen
authors: E
authors: Vitetta
authors: Amit
authors: A
authors: Verma
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018941:Antigens, CD19 / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012008:Recurrence; D012276:Ricin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D000970:Antineoplastic Agents; C497867:CD22 protein, human; D000922:Immunotoxins; D051918:Sialic Acid Binding Ig-like Lectin 2; D012276:Ricin