Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemia

J Clin Oncol. 2009 Jun 20;27(18):2983-90. doi: 10.1200/JCO.2008.20.2630. Epub 2009 May 4.

Abstract

Purpose: To conduct a phase II trial in chemoresistant hairy cell leukemia (HCL) with BL22, a recombinant anti-CD22 immunotoxin which showed phase I activity in HCL.

Patients and methods: Eligible patients had relapsed/refractory HCL and needed treatment based on blood counts. Patients were stratified into three groups: response to cladribine less than 1 year, those with a response lasting 1 to 4 years, or no response and uncontrolled infection. Patients received BL22 40 microg/kg every other day for three doses on cycle 1. Those achieving hematologic remission (HR), defined as neutrophils > or = 1,500/mm(3), hemoglobin > or = 11 g/dL, and platelets > or = 100,000/mm(3), were observed. Patients without HR were re-treated at 30 microg/kg every other day for three doses every 4 weeks beginning at least 8 weeks after cycle 1.

Results: Thirty-six patients were enrolled including 26, nine, and one in groups 1 to 3. The response after one cycle (CR, 25%; PR, 25%) improved when 56% were re-treated (CR, 47%; PR, 25%). CR rate was similar in groups 1 and 2 (P = .7). Twenty-two with baseline spleen height lower than 200 mm had higher CR (64% v 21%; P = .019) and OR rates (95% v 36%; P = .0002) compared to 14 with spleens either absent or higher than 200 mm. The only serious toxicity was reversible grade 3 hemolytic uremic syndrome, not requiring plasmapheresis, in two patients (6%). High neutralizing antibodies were observed in four patients (11%) and prevented re-treatment.

Conclusion: BL22 activity in HCL is confirmed. Best responses to BL22 after cladribine failure are achieved before the patients develop massive splenomegaly or undergo splenectomy.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Antibodies / administration & dosage
  • Antibodies / therapeutic use*
  • Antibodies / toxicity
  • Antineoplastic Agents / therapeutic use
  • Cladribine / therapeutic use
  • Drug Resistance
  • Enterotoxins / administration & dosage
  • Enterotoxins / pharmacokinetics
  • Enterotoxins / therapeutic use*
  • Enterotoxins / toxicity
  • Female
  • Humans
  • Leukemia, Hairy Cell / drug therapy*
  • Male
  • Middle Aged
  • Prospective Studies
  • Spleen
  • Treatment Outcome

Substances

  • Antibodies
  • Antineoplastic Agents
  • Enterotoxins
  • RFB4(dsFv)-PE38 recombinant immunotoxin
  • Cladribine