Originally published as JCO Early Release 10.1200/JCO.2008.20.2630 on May 4 2009

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Phase II Trial of Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) in Patients With Hairy Cell Leukemia

From the Laboratory of Molecular Biology, Laboratory of Clinical Pathology, and Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Corresponding author: Robert J. Kreitman, MD, National Cancer Institute, 9000 Rockville Pk, Bldg 37/5124b, Bethesda, MD 20892; e-mail: kreitmar{at}mail.nih.gov.

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 µg/kg every other day for three doses on cycle 1. Those achieving hematologic remission (HR), defined as neutrophils 1,500/mm³, hemoglobin 11 g/dL, and platelets 100,000/mm³, were observed. Patients without HR were re-treated at 30 µg/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.

Supported by the Intramural Research Program, National Institutes of Health, National Cancer Institute; and MedImmune Inc.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00074048 [ClinicalTrials.gov] .

Published by the American Society of Clinical Oncology

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