Phase I/II trial of PIXY321 (granulocyte-macrophage colony stimulating factor/interleukin-3 fusion protein) for treatment of inherited and acquired marrow failure syndromes.

Fourteen paediatric patients with advanced amegakaryocytic thrombocytopenia (AMT) or other bone marrow (BM) failure syndromes were enrolled on one of two phase I/II dose escalation studies of PIXY321. PIXY321 was administered subcutaneously in doses ranging from 250 to 750 mg/m2/d. No dose-limiting toxicity was observed. Peak absolute neutrophil count (ANC) was higher than baseline in all patients. Most transfusion-independent patients demonstrated elevation in haematocrit and/or platelet count. Trilineage haemopoietic responsiveness was evident in the three transfusion-independent patients. In these paediatric populations PIXY321 is well tolerated and merits consideration as a potential therapy.