Phase I-II study of bendamustine in patients with acute leukemia and high risk myelodysplastic syndrome

Christelle Chacar, Elias Jabbour, Farhad Ravandi, Gautam Borthakur, Tapan Kadia, Zeev Estrov, Mary Beth Rios, Jorge Cortes, Hagop Kantarjian

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: Alkylating agents have shown activity in leukemia. Bendamustine, an active alkylating agent in lymphoma and chronic lymphocytic leukemia, was given in a fractionated twice daily schedule for 4 days to patients with acute leukemia and myelodysplastic syndrome (MDS) to define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD). Patients and Methods: Adults with refractory acute leukemia or high-risk MDS were treated with bendamustine at a starting dose of 50 mg/m2 IV over 1-2 hours twice daily for 4 days. Dose escalations were by 25 mg/m2 in the 1st 3 levels. The study used the 3 + 3 design. Results: A total of 25 patients were treated. Their median age was 57 years; the median salvage number was 3. Grade 2 creatinine elevations were observed in 1 of 6 patients at the 50 mg/m 2 dose, in 2 of 13 patients at the 75 mg/m2 dose, and in 3 of 6 patients at the 100 mg/m2 dose. This was considered significant, even though DLT was not reached. One patient achieved marrow complete remission. Significant reductions of marrow blasts (50% or more) were observed in 6 of 25 patients (24%). Conclusion: Bendamustine fractionated dose level of 100 mg/m2 IV twice daily for 4 days (800 mg/m2 per course) was associated with Grade 2 renal toxicity. The proposed phase II schedule is 75 mg/m2 IV twice daily for 4 days. Future studies should evaluate this schedule in less heavily treated patients.

Original languageEnglish (US)
Pages (from-to)197-200
Number of pages4
JournalClinical Lymphoma, Myeloma and Leukemia
Volume12
Issue number3
DOIs
Publication statusPublished - Jun 1 2012
Externally publishedYes

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Keywords

  • Fractionated dose schedule

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Chacar, C., Jabbour, E., Ravandi, F., Borthakur, G., Kadia, T., Estrov, Z., ... Kantarjian, H. (2012). Phase I-II study of bendamustine in patients with acute leukemia and high risk myelodysplastic syndrome. Clinical Lymphoma, Myeloma and Leukemia, 12(3), 197-200. https://doi.org/10.1016/j.clml.2012.03.004