Results of a phase 1 clinical trial of thalidomide in combination with fludarabine as initial therapy for patients with treatment-requiring chronic lymphocytic leukemia (CLL)

Asher Chanan-Khan, Kena C. Miller, Kenichi Takeshita, Alexandra Koryzna, Kathleen Donohue, Zale P. Bernstein, Alice Mohr, Donald Klippenstein, Paul Wallace, Jerome B. Zeldis, Christine Berger, Myron S. Czuczman

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87 Scopus citations

Abstract

Tumor necrosis factor α (TNF-α) and vascular endothelial growth factor (VEGF) play an important role in the biology of chronic lymphocytic leukemia (CLL) cells. Thalidomide is a first-generation immunomodulating agent that down-regulates TNF-α and VEGF. We initiated a phase 1/2 clinical trial to determine the safety and efficacy of combining thalidomide with fludarabine in patients with treatment-naïve CLL. Patients received 6 months of continuous daily thalidomide with standard monthly doses of fludarabine. Three dose levels of thalidomide (100, 200, and 300 mg) were studied. Results from the phase 1 part of this study are reported here. Thirteen patients were enrolled in the phase 1 component of the study. Dose-limiting toxicity was not reached. The most common toxicities noted were fatigue, constipation, and peripheral sensory neuropathy. Overall response rate was 100% with 55% of patients achieving complete remissions. At a median follow-up of 15+ months none of the patients have had a relapse and the median time to disease progression has not yet been reached. Responses were noted at all dose levels. Thalidomide given up to 300 mg/day concurrently with fludarabine in patients with previously untreated CLL shows encouraging clinical efficacy and acceptable toxicity. An ongoing phase 2 part of this study will help validate the clinical efficacy of this regimen.

Original languageEnglish (US)
Pages (from-to)3348-3352
Number of pages5
JournalBlood
Volume106
Issue number10
DOIs
StatePublished - Nov 15 2005

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Chanan-Khan, A., Miller, K. C., Takeshita, K., Koryzna, A., Donohue, K., Bernstein, Z. P., Mohr, A., Klippenstein, D., Wallace, P., Zeldis, J. B., Berger, C., & Czuczman, M. S. (2005). Results of a phase 1 clinical trial of thalidomide in combination with fludarabine as initial therapy for patients with treatment-requiring chronic lymphocytic leukemia (CLL). Blood, 106(10), 3348-3352. https://doi.org/10.1182/blood-2005-02-0669