Remission re‐induction chemotherapy with clofarabine, topotecan, thiotepa, and vinorelbine for patients with relapsed or refractory leukemia
- 4 March 2010
- journal article
- research article
- Published by Wiley in Pediatric Blood & Cancer
- Vol. 54 (5) , 687-693
Abstract
Background We determined the maximum tolerated dose (MTD) of clofarabine when administered with topotecan, vinorelbine, thiotepa, and dexamethasone (TVTC) for children with relapsed or refractory acute leukemia, and observed the efficacy and toxicities of this therapy. Procedure Twelve patients with acute lymphoblastic or myeloblastic leukemia were given a 14-day remission induction therapy. Clofarabine was administered at a dose of 30 or 40 mg/m2/day over 2 hr for five consecutive days in six patients each. Patients who achieved a remission proceeded to a stem cell transplant (HSCT). A second cycle could be administered prior to HSCT. Results Of the six patients at the 30 mg/m2 clofarabine dose, two achieved a complete response (CR) and one a PR and proceeded to BMT. Three patients had progressive disease. Five of the six patients at the 40 mg/m2 achieved a CR. Four proceeded to HSCT, and one relapsed prior to HSCT. One patient died on day 45 with marrow hypoplasia without evidence of leukemia. Hematologic and infectious adverse events were universal. The one dose limiting non-infectious toxicity observed was prolonged marrow hypoplasia. Conclusion TVTC has significant anti-leukemic activity in both acute lymphoblastic and myeloblastic leukemia. The MTD of clofarabine is 40 mg/m2/day in this combination. This is the recommended dose for the phase II study in patients with refractory or relapsed leukemia, a population which has limited therapeutic options. Pediatr Blood Cancer 2010;54:687–693.Keywords
This publication has 25 references indexed in Scilit:
- Phase II Study of Clofarabine in Pediatric Patients With Refractory or Relapsed Acute Myeloid LeukemiaJournal of Clinical Oncology, 2009
- A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemiaLeukemia, 2009
- Clofarabine Induced Durable Complete Remission in Heavily Pretreated Adolescents With Relapsed and Refractory LeukemiaJournal of Pediatric Hematology/Oncology, 2007
- Phase II Study of Clofarabine in Pediatric Patients With Refractory or Relapsed Acute Lymphoblastic LeukemiaJournal of Clinical Oncology, 2006
- Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemiaBlood, 2004
- Phase I Study of Gemcitabine (Difluorodeoxycytidine) in Children with Relapsed or Refractory Leukemia (CCG-0955): A Report from the Children's Cancer GroupLeukemia & Lymphoma, 2002
- Pediatric Phase II Cancer Chemotherapy TrialsJournal of Pediatric Hematology/Oncology, 1997
- Cytosine arabinoside and mitoxantrone treatment of relapsed or refractory childhood leukemia: Initial response and relationship to multidrug resistance gene 1Medical and Pediatric Oncology, 1994
- Treatment of relapsed or refractory acute leukemia in childhood with bisantrene combined with high dose aracytineMedical and Pediatric Oncology, 1994
- Typhlitis in Children with Cancer: A 30-Year ExperienceClinical Infectious Diseases, 1993