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A phase II study of continuous infusion homoharringtonine and cytarabine in newly diagnosed patients with chronic myeloid leukemia: CALGB study 19804

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Abstract

Background

Both homoharringtonine (HHT), an alkaloid derivative from the Chinese yew tree that inhibits protein synthesis, and low-dose cytarabine have independent activity in CML and have been used in combination after failure of interferon therapy.

Patients and methods

The CALGB performed a phase II trial of HHT (2.5 mg/m2 per day) plus cytarabine (7.5 mg/m2 per day), given together via continuous intravenous infusion for 7 days in previously untreated patients with Ph chromosome positive chronic phase CML. HHT/cytarabine cycles were repeated every 28 days if the blood counts were adequate. The primary endpoint was the major cytogenetic response rate after 9 months.

Results

Forty of the 44 enrolled patients required reduction in the infusion duration during at least one cycle. Myelosuppression was common; 66% developed neutrophil count <500/μl, but grade 3 infections occurred in only 7%. Thirty-six of 44 patients (82%) achieved a complete hematologic remission; the median duration has not been reached. Only 4 of the 23 patients (17%) having adequate cytogenetic response assessment achieved a major response within nine cycles.

Conclusions

Although HHT/cytarabine was generally well tolerated, the cytogenetic response rate did not exceed the level previously seen in patients with interferon-refractory CML and was not nearly as high as associated with imatinib in newly diagnosed patients.

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Acknowledgments

This research was supported in part by grant CA 33601 from the National Cancer Institute. The research for CALGB 19804 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman) and to the CALGB Statistical center (Steven George, PhD, CA33601).

Author information

Authors and Affiliations

  1. Dana-Farber Cancer Institute, Room M1B-17, 44 Binney St, Boston, MA, 02115, USA

    Richard M. Stone & Daniel J. DeAngelo

  2. Cancer and Leukemia Group B (CALGB) Statistical Center, Duke University, Durham, NC, USA

    Kathleen A. Donohue & Vera Hars

  3. University of Chicago, Chicago, IL, USA

    Wendy Stock & Richard A. Larson

  4. University of California at San Francisco, San Francisco, CA, USA

    Charles A. Linker

  5. University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Thomas Shea

  6. The Ohio State University, Columbus, OH, USA

    Guido Marcucci & Clara D. Bloomfield

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  1. Richard M. Stone
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  2. Kathleen A. Donohue
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  3. Wendy Stock
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  4. Vera Hars
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  5. Charles A. Linker
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  7. Daniel J. DeAngelo
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  9. Clara D. Bloomfield
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  10. Richard A. Larson
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for the Cancer and Leukemia Group B

Corresponding author

Correspondence to Richard M. Stone.

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The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.

Appendix

Appendix

The following institutions participated in this study:

  • The CALGB Statistical Center, Duke University Medical Center, Durham, NC-Stephen George, Ph.D., supported by CA33601

  • Christiana Care Health Services, Inc. CCOP, Wilmington, DE-Stephen Grubbs, M.D., supported by CA45418

  • Dana-Farber Cancer Institute, Boston, MA-Eric P Winer, M.D., supported by CA32291

  • Duke University Medical center, Durham, NC-Jeffrey Crawford, M.D., supported by CA47577

  • Medical University of South Carolina, Charleston, SC-Mark Green, M.D. supported by CA03927

  • Roswell Park Cancer Institute, Buffalo, NY-Ellis Levine, M.D., supported by CA02599

  • The Ohio State University Medical Center, Columbus, OH-Clara D Bloomfield, M.D., supported by CA77658

  • University of California at San Diego, San Diego, CA-Joannne Mortimer, M.D., supported by CA11789

  • University of California at San Francisco, San Francisco, CA-Alan P. Venook, M.D., supported by CA60138

  • University of Chicago, Chicago, IL-Gini Fleming, M.D., supported by CA41287

  • University of Illinois MBCCOP, Chicago, IL-Lawrence E. Feldman, M.D., supported by CA74811

  • University of Maryland Greenebaum Cancer Center, Baltimore, MD-Martin Edelman, M.D., supported by CA31983

  • University of North Carolina at Chapel Hill, Chapel Hill, NC-Thomas C. Shea, M.D., supported by CA47559

  • University of Tennessee Memphis, Memphis, TN-Harvey B. Niell, M.D., supported by CA47555

  • Wake Forest University School of Medicine, Winston-Salem, NC-David D Hurd, M.D., supported by CA03927

  • Washington University School of Medicine, St. Louis, MO-Nancy Bartlett, M.D., supported by CA77440.

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Stone, R.M., Donohue, K.A., Stock, W. et al. A phase II study of continuous infusion homoharringtonine and cytarabine in newly diagnosed patients with chronic myeloid leukemia: CALGB study 19804. Cancer Chemother Pharmacol 63, 859–864 (2009). https://doi.org/10.1007/s00280-008-0805-8

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