title: A phase 1 study of Combotox in pediatric patients with refractory B-lineage acute lymphoblastic leukemia.
abstract: BACKGROUND
  Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Combotox is a 1:1 mixture of RFB4-dgA and HD37-dgA which are immunotoxins that target the CD22 and CD19 antigens, respectively. Combotox has different toxicities and targets than chemotherapy and is, thus, a new candidate for the treatment of patients with relapsed ALL. Preclinical data have demonstrated which Combotox is effective in killing pre-B-ALL cell lines and cells from patients with pre-B ALL.
  
  
  METHODS
  We designed and conducted a Phase 1 dose-escalation study using Combotox in children with refractory or relapsed B-lineage-ALL. Seventeen patients aged 1 to 16 years were enrolled in this multi-institution study. They were treated at 4-dose levels: 2 mg/m2, 4 mg/m2, 5 mg/m2, and 6 mg/m2.
  
  
  RESULTS
  The maximum tolerated dose was 5 mg/m2 and graft versus host disease defined the maximum tolerated dose. Three patients experienced complete remission. Six additional patients experienced a decrease of >95% in their peripheral blood blast counts, and 1 patient experienced a decrease of 75%.
  
  
  CONCLUSIONS
  Combotox can be safely administered to children with refractory leukemia. It has clinically important anticancer activity as a single agent. The recommended dose for future studies is 5 mg/m2/dose.
authors.affiliation: Temple University, Philadelphia, PA, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Herrera
authors.forename: Bruce
authors.initials: B
authors.lastname: Bostrom
authors.forename: Lisa
authors.initials: L
authors.lastname: Gore
authors.forename: Eric
authors.initials: E
authors.lastname: Sandler
authors.forename: Glen
authors.initials: G
authors.lastname: Lew
authors.forename: Paul G
authors.initials: PG
authors.lastname: Schlegel
authors.forename: Victor
authors.initials: V
authors.lastname: Aquino
authors.forename: Victor
authors.initials: V
authors.lastname: Ghetie
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Vitetta
authors.forename: John
authors.initials: J
authors.lastname: Schindler
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018941:Antigens, CD19 / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D012276:Ricin / Q000627:therapeutic use*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; C497867:CD22 protein, human; D000922:Immunotoxins; D051918:Sialic Acid Binding Ig-like Lectin 2; D012276:Ricin