International Journal of Hematology

DOI: 10.1007/s12185-017-2327-9 Pages: 83-91

Phase I study of panobinostat and 5-azacitidine in Japanese patients with myelodysplastic syndrome or chronic myelomonocytic leukemia

1. National Cancer Center Hospital, Department of Hematology

2. International University of Health and Welfare, Mita Hospital, Department of Hematology

3. Japanese Red Cross Nagoya Daini Hospital, Department of Hematology and Oncology

4. Tokai Central Hospital, Department of Hematology

5. Kyoto Prefectural University of Medicine, Department of Hematology and Oncology, University Hospital

6. Novartis Pharma K.K., Oncology Department

7. Kobe University Hospital, Department of Medical Oncology and Hematology

Correspondence to:
Yukio Kobayashi
Tel: +81-3-3451-8121



The current therapy for high-risk myelodysplastic syndrome (MDS) involves repeated cycles of the DNA demethylating agent 5-azacitidine (5-Aza), but combination treatments have been proposed to improve patient outcomes. We performed a phase Ib study to investigate the safety and tolerability of 5-Aza (75 mg/m2) combined with the histone deacetylase inhibitor panobinostat (PAN) in adult Japanese patients with MDS or chronic myelomonocytic leukemia (CMML). Eleven patients were enrolled; five received 20 mg PAN + 5-Aza and six received 30 mg PAN + 5-Aza. All patients in the 20 mg PAN cohort had MDS, while two in the 30 mg PAN cohort had MDS and three had CMML. All patients experienced ≥1 adverse event (AE) related to the study treatment, and five discontinued the study treatment because of AEs. One patient in each group exhibited dose-limiting toxicities: lung infection (PAN 20 mg + 5-Aza) and cellulitis (PAN 30 mg + 5-Aza). PAN exposure increased with ascending doses, and combination therapy did not affect PAN plasma trough concentrations. In summary, 20 or 30 mg PAN combined with 5-Aza was safe and tolerable in adult Japanese patients with CMML or MDS.

Study registration Identifier: NCT01613976.

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