Phase II trial of clofarabine with topotecan, vinorelbine, and thiotepa in pediatric patients with relapsed or refractory acute leukemia Journal Article


Authors: Shukla, N.; Kobos, R.; Renaud, T.; Steinherz, L. J.; Steinherz, P. G.
Article Title: Phase II trial of clofarabine with topotecan, vinorelbine, and thiotepa in pediatric patients with relapsed or refractory acute leukemia
Abstract: 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 40mg/m2/day IV×5 days, topotecan 1mg/m2/day IV continuous infusion×5 days, vinorelbine 20mg/m2/week IV×3 weeks, thiotepa 15mg/m2/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. © 2013 Wiley Periodicals, Inc.
Keywords: leukemia; pediatric; clofarabine; refractory; relapsed
Journal Title: Pediatric Blood and Cancer
Volume: 61
Issue: 3
ISSN: 1545-5009
Publisher: Wiley Periodicals, Inc  
Date Published: 2014-03-01
Start Page: 431
End Page: 435
Language: English
DOI: 10.1002/pbc.24789
PROVIDER: scopus
PUBMED: 24115731
DOI/URL:
Notes: Export Date: 3 March 2014 -- CODEN: PBCEA -- Source: Scopus
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MSK Authors
  1. Peter G Steinherz
    179 Steinherz
  2. Thomas Merriam Renaud
    17 Renaud
  3. Rachel Kobos
    65 Kobos
  4. Neerav Shukla
    83 Shukla