Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy

Blood. 2010 Oct 28;116(17):3163-70. doi: 10.1182/blood-2010-03-274753. Epub 2010 Jul 14.

Abstract

We evaluated the efficacy and safety of romiplostim, a thrombopoietin mimetic, in patients with low- or intermediate-risk myelodysplastic syndromes (MDS) receiving azacitidine therapy. Forty patients with low- or intermediate-risk MDS were stratified by baseline platelet counts (< 50 vs ≥ 50 × 10(9)/L) and randomized to romiplostim 500 μg or 750 μg or placebo subcutaneously once weekly during 4 cycles of azacitidine. The primary endpoint was the incidence of clinically significant thrombocytopenic events, defined by grade 3 or 4 thrombocytopenia starting on day 15 of the first cycle or platelet transfusion at any time during the 4-cycle treatment period. No formal hypothesis testing was planned. The incidence of clinically significant thrombocytopenic events in patients receiving romiplostim 500 μg, romiplostim 750 μg, or placebo was 62%, 71%, and 85%, respectively. The incidence of platelet transfusions was 46%, 36%, and 69%, respectively. These differences were not statistically significant with the small numbers in each group. Romiplostim 750 μg significantly raised median platelet counts during cycle 3 on day 1 (P = .0373) and at the nadir (P = .0035) compared with placebo. Grade 3 rash and arthralgia each were reported in 1 romiplostim-treated patient (4%). This study suggests romiplostim may provide clinical benefits in MDS patients during azacitidine therapy.

Trial registration: ClinicalTrials.gov NCT00321711.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Azacitidine / therapeutic use*
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / complications*
  • Myelodysplastic Syndromes / drug therapy*
  • Receptors, Fc / therapeutic use*
  • Receptors, Thrombopoietin / agonists*
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use*
  • Thrombocytopenia / complications
  • Thrombocytopenia / epidemiology
  • Thrombocytopenia / prevention & control*
  • Thrombopoietin / adverse effects
  • Thrombopoietin / therapeutic use*

Substances

  • Antimetabolites, Antineoplastic
  • Receptors, Fc
  • Receptors, Thrombopoietin
  • Recombinant Fusion Proteins
  • Thrombopoietin
  • romiplostim
  • Azacitidine

Associated data

  • ClinicalTrials.gov/NCT00321711