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

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.

• Authors: Robert J Kreitman, Maryalice Stetler-Stevenson, Inger Margulies, Pierre Noel, David J P Fitzgerald, Wyndham H Wilson, Ira Pastan
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 18 Pg. 2983-90 (Jun 20 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19414673 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Intramural)

Chemical References

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

Topics

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