Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia.

Abstract

PURPOSE:

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).

PATIENTS AND 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.

CONCLUSION:

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: Robert J Kreitman, Martin S Tallman, Tadeusz Robak, Steven Coutre, Wyndham H Wilson, Maryalice Stetler-Stevenson, David J Fitzgerald, Robert Lechleider, Ira Pastan
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 30 Issue 15 Pg. 1822-8 (May 20 2012) ISSN: 1527-7755 [Electronic] United States
• PMID: 22355053 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Webcast)

Chemical References

• Bacterial Toxins
• CD22 protein, human
• Exotoxins
• Sialic Acid Binding Ig-like Lectin 2
• immunotoxin HA22

Topics

• Adult
• Aged
• Bacterial Toxins (adverse effects, therapeutic use)
• Disease-Free Survival
• Drug Resistance, Neoplasm
• Exotoxins (adverse effects, therapeutic use)
• Female
• Humans
• Immunotherapy (adverse effects, methods)
• Leukemia, Hairy Cell (immunology, pathology, therapy)
• Male
• Middle Aged
• Sialic Acid Binding Ig-like Lectin 2 (immunology)
• Time Factors
• Treatment Outcome