title: Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies.
abstract: OBJECTIVE
  To conduct a phase I trial of recombinant immunotoxin BL22, an anti-CD22 Fv fragment fused to truncated Pseudomonas exotoxin.
  
  
  METHODS
  Forty-six pretreated patients with CD22+ non-Hodgkin's lymphoma (NHL; n = 4), chronic lymphocytic leukemia (CLL; n = 11), and hairy cell leukemia (HCL; n = 31) received 265 cycles at 3 to 50 microg/Kg every other day x 3 doses.
  
  
  RESULTS
  BL22 was active in HCL, with 19 complete remissions (CRs; 61%) and six partial responses (PRs; 19%) in 31 patients. Of 19 CRs, 11 were achieved after one cycle and eight after two to 14 cycles. All 25 responders benefited clinically with one cycle. The CR rate was 86% in patients enrolled at > or = 40 microg/Kg every other day x 3, and 41% at lower doses (P = .011). The median duration for CR was 36 months (range, 5 to 66 months), and eight patients remain in CR at 45 months (range, 29 to 66 months). Lower but significant activity occurred in CLL. Neutralizing antibodies occurred in 11 (24%) of 46 patients (all HCL). A reversible hemolytic uremic syndrome requiring plasmapheresis was observed in one patient with NHL during cycle 1 and in four patients with HCL during cycle 2 or 3. The maximum-tolerated dose (MTD) evaluated at cycle 1 was 40 microg/Kg IV. QOD x 3. The most common toxicities at 30 to 50 microg/Kg every other day x 3 included hypoalbuminemia, transaminase elevations, fatigue, and edema.
  
  
  CONCLUSIONS
  BL22 was well tolerated and highly effective in HCL, even after one cycle. Phase II testing is underway to define the efficacy with one cycle and to study safety when additional cycles are needed for optimal response.
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bldg 5124b, 9000 Rockville Pike, Bethesda, MD 20892, USA. kreitmar@mail.nih.gov
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kreitman
authors.forename: David R
authors.initials: DR
authors.lastname: Squires
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: Pierre
authors.initials: P
authors.lastname: Noel
authors.forename: David J P
authors.initials: DJ
authors.lastname: FitzGerald
authors.forename: Wyndham H
authors.initials: WH
authors.lastname: Wilson
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004768:Enterotoxins; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007943:Leukemia, Hairy Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D004768:Enterotoxins; D000922:Immunotoxins; C431326:RFB4(dsFv)-PE38 recombinant immunotoxin