Phase I Trial of Anti-CD22 Recombinant Immunotoxin Moxetumomab Pasudotox (CAT-8015 or HA22) in Patients With Hairy Cell Leukemia
- 20 May 2012
- journal article
- webcast
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 30 (15), 1822-1828
- https://doi.org/10.1200/jco.2011.38.1756
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.Keywords
This publication has 29 references indexed in Scilit:
- Thrombotic Microangiopathy with Targeted Cancer AgentsClinical Cancer Research, 2011
- Phase I Trial of Continuous Infusion Anti-Mesothelin Recombinant Immunotoxin SS1PClinical Cancer Research, 2009
- Phase II Trial of Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) in Patients With Hairy Cell LeukemiaJournal of Clinical Oncology, 2009
- Long‐term follow‐up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosisBritish Journal of Haematology, 2009
- A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicityBlood, 2009
- CAT-8015: A Second-GenerationPseudomonasExotoxin A–Based Immunotherapy Targeting CD22-Expressing Hematologic MalignanciesClinical Cancer Research, 2009
- Phase I Study of SS1P, a Recombinant Anti-Mesothelin Immunotoxin Given as a Bolus I.V. Infusion to Patients with Mesothelin-Expressing Mesothelioma, Ovarian, and Pancreatic CancersClinical Cancer Research, 2007
- Phase I Trial of Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) in Patients With B-Cell MalignanciesJournal of Clinical Oncology, 2005
- Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemiaBlood, 2003
- Response duration and recovery of CD4+ lymphocytes following deoxycoformycin in interferon-α-resistant hairy cell leukemia: 7-year follow-upLeukemia, 1997