title: Initial experience with CMC-544 (inotuzumab ozogamicin) in pediatric patients with relapsed B-cell acute lymphoblastic leukemia.
abstract: Survival is poor in pediatric patients with relapsed or refractory acute B-cell lymphoblastic leukemia (ALL) and therapeutic options are limited. CMC-544 (inotuzumab ozogamicin) has shown significant activity in adult patients with relapsed and refractory ALL. We evaluated CMC-544 in pediatric patients with multiply relapsed ALL. Five children 4-15 years old with relapsed, CD 22 positive B-cell ALL were enrolled on a phase II non-randomized trial of CMC-544. CMC-544 was initially administered at 1.3 mg/m(2) every 3 weeks. The dose then increased to 1.8 mg/m(2) every 3 weeks. Subsequently, a weekly schedule of CMC-544 given as 0.8 mg/m(2) on day 1 followed by 0.5 mg/m(2) on days 8 and 15 was administered. All five patients had refractory relapsed B-cell ALL. Lymphoblasts for all patients highly expressed CD22. Four patients had two or more relapses before starting the study drug. One patient achieved a complete remission in the bone marrow and normal peripheral counts, and two patients achieved bone marrow morphologic remission with absolute neutrophils >1,000/µl but platelets <100,000/µl. Two patients had no response to the drug. Toxicities consisted of fever, sepsis, and liver enzyme elevation. Single agent CMC-544 given at the single dose of 1.8 mg/m(2) every 3 weeks or given as a split, weekly dose was generally well tolerated considering the inherent risks in this population of patients and showed promising activity in pediatric patients with relapsed and refractory ALL.
authors.affiliation: Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Texas; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Texas.
authors.forename: Michael
authors.initials: M
authors.lastname: Rytting
authors.forename: Lisa
authors.initials: L
authors.lastname: Triche
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000080045:Inotuzumab Ozogamicin; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000080045:Inotuzumab Ozogamicin
keywords: CD 22; CMC-544; acute lymphoblastic leukemia; relapse