title: Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia.
abstract: OBJECTIVE
  To conduct a phase I dose-escalation trial assessing safety and response of recombinant immunotoxin moxetumomab pasudotox (CAT-8015, HA22) in chemotherapy-resistant hairy cell leukemia (HCL).
  
  
  METHODS
  Eligible patients had relapsed/refractory HCL after ≥ two prior therapies and required treatment because of abnormal blood counts. Patients received moxetumomab pasudotox 5 to 50 μg/kg every other day for three doses (QOD ×3), with up to 16 cycles repeating at ≥ 4-week intervals if patients did not experience disease progression or develop neutralizing antibodies.
  
  
  RESULTS
  Twenty-eight patients were enrolled, including three patients each at 5, 10, 20, and 30 μg/kg, four patients at 40 μg/kg, and 12 patients at 50 μg/kg QOD ×3 for one to 16 cycles each (median, four cycles). Dose-limiting toxicity was not observed. Two patients had transient laboratory abnormalities consistent with grade 2 hemolytic uremic syndrome with peak creatinine of 1.53 to 1.66 mg/dL and platelet nadir of 106,000 to 120,000/μL. Drug-related toxicities in 25% to 64% of the 28 patients included (in decreasing frequency) grade 1 to 2 hypoalbuminemia, aminotransferase elevations, edema, headache, hypotension, nausea, and fatigue. Of 26 patients evaluable for immunogenicity, 10 patients (38%) made antibodies neutralizing more than 75% of the cytotoxicity of 1,000 ng/mL of immunotoxin, but this immunogenicity was rare (5%) after cycle 1. The overall response rate was 86%, with responses observed at all dose levels, and 13 patients (46%) achieved complete remission (CR). Only 1 CR lasted less than 1 year, with the median disease-free survival time not yet reached at 26 months.
  
  
  CONCLUSIONS
  Moxetumomab pasudotox at doses up to 50 μg/kg QOD ×3 has activity in relapsed/refractory HCL and has a safety profile that supports further clinical development for treatment of this disease.
authors.affiliation: National Cancer Institute, National Institutesof Health, Bethesda, USA. kreitmar@mail.nih.gov
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kreitman
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Steven
authors.initials: S
authors.lastname: Coutre
authors.forename: Wyndham H
authors.initials: WH
authors.lastname: Wilson
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: David J
authors.initials: DJ
authors.lastname: Fitzgerald
authors.forename: Robert
authors.initials: R
authors.lastname: Lechleider
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
mesh_terms: D000328:Adult; D000368:Aged; D001427:Bacterial Toxins / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005098:Exotoxins / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D007943:Leukemia, Hairy Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001427:Bacterial Toxins; C497867:CD22 protein, human; D005098:Exotoxins; D051918:Sialic Acid Binding Ig-like Lectin 2; C541974:immunotoxin HA22