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Results from an international phase 2 study of the anti‐CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B‐lineage acute lymphoblastic leukemia
Author(s) -
Shah Nirali N.,
Bhojwani Deepa,
August Keith,
Baruchel André,
Bertrand Yves,
Boklan Jessica,
DallaPozza Luciano,
Dennis Robyn,
Hijiya Nobuko,
Locatelli Franco,
Martin Paul L.,
Mechinaud Françoise,
Moppett John,
Rheingold Susan R.,
Schmitt Claudine,
Trippett Tanya M.,
Liang Meina,
Balic Kemal,
Li Xia,
Vainshtein Inna,
Yao Nai Shun,
Pastan Ira,
Wayne Alan S.
Publication year - 2020
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.28112
Subject(s) - medicine , refractory (planetary science) , phases of clinical research , interim analysis , tumor lysis syndrome , gastroenterology , adverse effect , clinical trial , oncology , chemotherapy , physics , astrobiology
Background In a multicenter phase 1 study of children with relapsed/refractory acute lymphoblastic leukemia (ALL), moxetumomab pasudotox, an anti‐CD22 immunotoxin, demonstrated a manageable safety profile and preliminary evidence of clinical activity. A phase 2 study further evaluated efficacy. Procedure This international, multicenter, phase 2 study enrolled children with relapsed/refractory B‐cell precursor ALL who received moxetumomab pasudotox 40 µg/kg intravenously every other day, for six doses per 21‐day cycle. The primary objective was to evaluate the complete response (CR) rate. Secondary objectives included safety, pharmacokinetics, and immunogenicity evaluations. Results Thirty‐two patients (median age, 10 years) were enrolled at 16 sites; 30 received study drug and were evaluable for safety; 28 were evaluable for response. The objective response rate was 28.6%, with three patients (10.7%) achieving morphologic CR, and five patients (17.9%) achieving partial response. Disease progression occurred in 11 patients (39.3%). Ten patients (33.3%) experienced at least one treatment‐related serious adverse event, including capillary leak syndrome (CLS; n = 6), hemolytic uremic syndrome (HUS; n = 4), and treatment‐related death ( n = 1) from pulmonary edema. No differences were observed in inflammatory markers in patients who did or did not develop CLS or HUS. Conclusions Despite a signal for clinical activity, this phase 2 study was terminated at interim analysis for a CR rate that did not reach the stage 1 target. Preclinical data suggest enhanced efficacy of moxetumomab pasudotox via continuous infusion or in combination regimens; thus, further studies designed to optimize the efficacy and safety of moxetumomab pasudotox in pediatric ALL may be warranted.