Phase I trial and pharmacokinetic study of high-dose clofarabine and busulfan and allogeneic stem cell transplantation in adults with high-risk and refractory acute leukemia

S. S. Farag, L. L. Wood, J. E. Schwartz, S. Srivastava, R. P. Nelson, M. J. Robertson, R. Abonour, A. Secrest, E. Cox, J. Baute, C. Sullivan, K. Kane, D. R. Jones

Research output: Contribution to journalArticle

28 Scopus citations


We conducted a phase I trial to determine the maximum tolerated dose (MTD) of clofarabine with high-dose busulfan followed by allogeneic stem cell transplantation (SCT) in patients with high-risk and refractory acute leukemia. Patients received intravenous busulfan 0.8 mg/kg every 6 h on days -6 to -3 and clofarabine 30-60 mg/m(2) per day on days -6 to -2. Graft-versus-host disease prophylaxis included sirolimus plus tacrolimus (days -2 to +180). A total of 15 patients, median age 48 (30-58) years, with acute leukemia that was relapsed and refractory (n=8), primary refractory (n=6), or in CR2 (n=1), were treated at four clofarabine dose levels: 30 (n=3), 40 (n=3), 50 (n=3) and 60 mg/m(2) per day (n=6) with busulfan. All engrafted, and the MTD was not reached. Grades 3-4 non-hematological toxicities included vomiting (n=3), mucositis (n=9), hand-foot syndrome (n=1), acute renal failure (n=1) and reversible elevation of aspartate aminotransferase/alanine aminotransferase (n=10). The 1-year event-free survival was 53% (95% confidence interval: 33-86%), and the 1-year overall survival was 60% (95% confidence interval: 40-91%). Given the good tolerability and promising results, we recommend clofarabine 60 mg/m(2) per day × 5 days as a phase II dose in combination with busulfan (12.8 mg per kg total dose) for further study as a myeloablative regimen for allogeneic SCT for high-risk acute leukemia.

Original languageEnglish (US)
Pages (from-to)599-605
Number of pages7
Issue number4
StatePublished - Apr 2011



  • Acute leukemia
  • Allogeneic hematopoietic cell transplantation
  • Busulfan
  • Clofarabine

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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