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Phase II trial of clofarabine with topotecan, vinorelbine, and thiotepa in pediatric patients with relapsed or refractory acute leukemia
Author(s) -
Shukla Neerav,
Kobos Rachel,
Renaud Thomas,
Steinherz Laurel J.,
Steinherz Peter G.
Publication year - 2014
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.24789
Subject(s) - medicine , clofarabine , neutropenia , leukemia , gastroenterology , regimen , acute leukemia , phases of clinical research , refractory (planetary science) , hematopoietic stem cell transplantation , cytarabine , transplantation , topotecan , vinorelbine , febrile neutropenia , surgery , oncology , chemotherapy , physics , astrobiology , cisplatin
Background Outcomes for children with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) are dismal. In an effort to improve outcomes, we performed a phase I/II study of a novel clofarabine based combination regimen called TVTC. Herein, we report the response rates of patients in the phase II portion of the study. Procedure Seventeen patients with R/R ALL, AML, or biphenotypic leukemia were enrolled. Sixteen patients were evaluable for response. Patients were treated at the maximum tolerated dose (MTD) from the phase I portion of the study (clofarabine 40 mg/m 2 /day IV × 5 days, topotecan 1 mg/m 2 /day IV continuous infusion × 5 days, vinorelbine 20 mg/m 2 /week IV × 3 weeks, thiotepa 15 mg/m 2 /day IV × 1 day). The primary endpoint was overall response rate (ORR), defined as CR or CR without platelet recovery (CRp). Results The ORR was 69% (10 CR, 1 CRp). Among the 11 responders, 9 (82%) proceeded to hematopoietic stem cell transplantation. The most common grade 3+ non‐hematologic toxicities were febrile neutropenia (82%) and transient transaminase elevation (47%). Conclusions TVTC demonstrates significant activity in patients with R/R acute leukemia. The activity in R/R AML patients was very encouraging, with 8 of 12 (67%) patients achieving a CR/CRp. Patients with high risk de novo AML may benefit from incorporation of TVTC therapy into frontline treatment regimens. This regimen warrants further exploration in a larger cohort of patients with R/R leukemia. Pediatr Blood Cancer 2014;61:431–435. © 2013 Wiley Periodicals, Inc.