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Acute myeloid leukemia

A clinical trial for patients with acute myeloid leukemia or myelodysplastic syndromes not eligible for standard clinical trials

Leukemia volume 31, pages 318–324 (2017)Cite this article

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A Corrigendum to this article was published on 24 March 2017

Abstract

Most clinical trials exclude patients with poor performance or comorbidities. To study whether patients with these characteristics can be treated within a clinical trial, we conducted a study for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) with poor performance, organ dysfunction or comorbidities. Primary endpoint was 60-day survival. Study included stopping rules for survival and response. Treatment consisted on a combination of azacitidine and vorinostat. Thirty patients (16 with MDS, 14 with AML) were enrolled. Median follow-up was 7.4 months (0.3–29). Sixty-day survival was 83%. No stopping rules were met. Main adverse events (AEs) were grades 1 and 2 gastrointestinal toxicities. In view of these results, we expanded the study and treated 79 additional patients: 27 with azacitidine (AZA) and 52 with azacitidine and vorinostat (AZA+V). Median follow-up was 22.7 months (12.6–47.5). Sixty-day survival rate was 79% (AZA=67%, AZA+V=85%, P=0.07). Median overall survival was 7.6 months (4.5–10.7). Median event-free survival was 4.5 months (3.5–5.6). Main AEs included grades 1 and 2 gastrointestinal toxicities. Our results suggest this subset of patients can be safely treated within clinical trials and derive clinical benefit. Relaxation of standard exclusion criteria may increase the pool of patients likely to benefit from therapy.

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Acknowledgements

Merck Sharp and Dohme Corporation supported this clinical trial (NCT00948064). Support for this project was also provided by a number of other sources, including the MD Anderson Cancer Center Support Grant P30 CA016672, the Dr Kenneth B McCredie Chair in Clinical Leukemia Research endowment, the Edward P Evans Foundation, the Fundacion Ramon Areces, the Cancer Prevention & Research Institute of Texas (CPRIT) award RP140500, and by generous philanthropic contributions to MD Anderson’s MDS/AML Moon Shot Program.

Author contributions

G Garcia-Manero, E Estey, C DiNardo, N Pemmaraju, N Daver, Z Estrov, J Cortes, Y Alvarado, S Verstovsek, N Jain, W Wierda, M Konopleva, E Jabbour, G Borthakur, T Kadia, F Ravandi and H Kantarjian designed the study, analyzed data, contributed patients and participated in writing the manuscript. X Huang and C Hsiang-Chun performed the statistical analysis and participated in statistical design. G Montalban-Bravo participated in data collection, analyzing the data and writing the manuscript. M Brant and S Pierce collected and analyzed data. C Bueso-Ramos performed histopathological analysis. H Yang performed correlative studies. C Foudray and T Sneed participated as the research nurses of the study.

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Authors and Affiliations

  1. Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    G Montalban-Bravo, E Jabbour, G Borthakur, C D DiNardo, N Pemmaraju, J Cortes, S Verstovsek, T Kadia, N Daver, W Wierda, Y Alvarado, M Konopleva, F Ravandi, Z Estrov, N Jain, A Alfonso, M Brandt, T Sneed, H Yang, S Pierce, E Estey, Z Bohannan, H M Kantarjian & G Garcia-Manero

  2. Department of Biostatistics, University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    X Huang & H-C Chen

  3. Department of Hematopathology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    C Bueso-Ramos

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  1. G Montalban-Bravo
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Corresponding author

Correspondence to G Garcia-Manero.

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Competing interests

GG-M work has been supported by Celgene, maker of azacitidine, and Merck, maker of vorinostat. Merck supported in part this study. GG-M has served as a consultant and speaker for both Celgene and Merck.

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Montalban-Bravo, G., Huang, X., Jabbour, E. et al. A clinical trial for patients with acute myeloid leukemia or myelodysplastic syndromes not eligible for standard clinical trials. Leukemia 31, 318–324 (2017). https://doi.org/10.1038/leu.2016.303

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