A Pilot Study of a Thrombopoietin-Receptor Agonist, Eltrombopag, in Patients With Low to Int-2 Risk Myelodysplastic Syndrome (MDS)

Summary

Background: * Myelodysplastic syndromes (MDS) are bone marrow disorders characterized by anemia, neutropenia, and thrombocytopenia (low red blood cell, white blood cell, and platelet counts). Patients with MDS are at risk for symptomatic anemia, infection, and bleeding, as well as a risk of progression to acute leukemia. Standard treatments for MDS have significant relapse rates. MDS patients with thrombocytopenia who fail standard therapies require regular, expensive, and inconvenient platelet transfusions, and are at risk for further serious bleeding complications. * Eltrombopag is a drug designed to mimic the protein thrombopoietin, which causes the body to make more platelets. Eltrombopag has been able to increase platelet counts in healthy volunteers and in patients with chronic ITP (a disease where patients destroy their own platelets very rapidly and thus develop thrombocytopenia), but researchers do not know if the drug can increase platelet counts in patients with MDS. Objectives: * To find out whether eltrombopag can improve platelet counts in patients with MDS. * To determine whether eltrombopag is safe for patients with MDS. Eligibility: * Patients 18 years of age and older who have consistently low blood platelet counts related to MDS that has not responded to conventional treatment. * Platelet count ≤ 30,000/μL or platelet-transfusion-dependence (requiring at least 4 platelet transfusions in the 8 weeks prior to study entry); OR hemoglobin less than 9.0 gr/dL or red cell transfusion-dependence (requiring at least 4 units of PRBCs in the eight weeks prior to study entry) OR ANC≤500 Design: * Treatment with eltrombopag tablets once per day for 16-20 weeks. * Participants will be monitored closely throughout the initial treatment, with weekly blood tests and separate evaluations at the National Institutes of Health (NIH) treatment center every 4 weeks. Bone marrow biopsies may be conducted to check for abnormalities in bone marrow. * If patients show signs of improved platelet counts after 90 days, treatment will continue with additional doses of eltrombopag. * Patients who discontinue taking eltrombopag will be evaluated at the NIH treatment center 4 weeks after ending treatment, and again 6 months after ending treatment to check for potential side effects.

Timeline

Start

2011-03-15

Primary completion

2017-08-10

Completion

2021-12-30

Publications

• Background Kantarjian H, Giles F, List A, Lyons R, Sekeres MA, Pierce S, Deuson R, Leveque J. The incidence and impact of thrombocytopenia in myelodysplastic syndromes. Cancer. 2007 May 1;109(9):1705-14. doi: 10.1002/cncr.22602.
• Background Houwerzijl EJ, Blom NR, van der Want JJ, Vellenga E, de Wolf JT. Megakaryocytic dysfunction in myelodysplastic syndromes and idiopathic thrombocytopenic purpura is in part due to different forms of cell death. Leukemia. 2006 Nov;20(11):1937-42. doi: 10.1038/sj.leu.2404385. Epub 2006 Sep 7.
• Background Kalina U, Hofmann WK, Koschmieder S, Wagner S, Kauschat D, Hoelzer D, Ottmann OG. Alteration of c-mpl-mediated signal transduction in CD34(+) cells from patients with myelodysplastic syndromes. Exp Hematol. 2000 Oct;28(10):1158-63. doi: 10.1016/s0301-472x(00)00527-0.
• Giudice V, Feng X, Lin Z, Hu W, Zhang F, Qiao W, Ibanez MDPF, Rios O, Young NS. Deep sequencing and flow cytometric characterization of expanded effector memory CD8+CD57+ T cells frequently reveals T-cell receptor Vbeta oligoclonality and CDR3 homology in acquired aplastic anemia. Haematologica. 2018 May;103(5):759-769. doi: 10.3324/haematol.2017.176701. Epub 2018 Feb 1.
• Hosokawa K, Kajigaya S, Feng X, Desierto MJ, Fernandez Ibanez MD, Rios O, Weinstein B, Scheinberg P, Townsley DM, Young NS. A plasma microRNA signature as a biomarker for acquired aplastic anemia. Haematologica. 2017 Jan;102(1):69-78. doi: 10.3324/haematol.2016.151076. Epub 2016 Sep 22.

Drugs

Indications