Phase I trial of recombinant fusion protein PIXY321 for mobilization of peripheral-blood cells

Purpose: Mobilization of peripheral-blood cells (PBC) with cytokines alone results in rapid hematopoietic recovery and avoids the potential morbidity associated with mobilization by chemotherapy. PIXY321, a fusion protein that consists of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), has enhanced hematopoietic colony-forming activity as compared with individual or equimolar combinations of the two cytokines. A phase I trial of PIXY321 for mobilization of PBC in patients with malignant lymphoma was performed. Patients and Methods: Thirteen patients with malignant lymphoma who were eligible for high-dose therapy (HDT) were enrolled onto the trial. All patients were ineligible for autologous bone marrow transplantation due to overt metastotic disease in the marrow or to severe marrow hypocellularity. PIXY321 was administered at three dose levels of 250, 500, and 750 μg/m²/d by continuous infusion until completion of PBC collections. Collections were initiated when the WBC count was greater than 10 x 10⁹/L or 4 days after the initiation of PIXY321, whichever came first. Collections were continued until a minimum of 6.5 x 10⁸ mononuclear cells (MNC)/kg patient weight were obtained. Results: PIXY321 was generally well tolerated. Side effects associated with PIXY321 administration did not exceed grade 2 and included fever (85%), chills/sweats (54%), myalgias (38%), fatigue (31%), nausea/vomiting (31%), headache (31%), edema (23%), and rhinorrhea (23%). The median numbers of colony-forming units-granulocyte/macrophage (CPU-GM) in the graft products for the three dose levels were 0.31, 2.94, and 2.88 x 10⁴/kg, respectively; the median numbers of burst-forming units-erythroid (BFU-e) were 0.20, 6.94, and 12.78 x 10⁴/kg, and the median numbers of CD34⁺ cells were 2.30, 0.74, and 0.39 x 10⁶/kg. Following transplantation, the median times to an absolute neutrophil count (ANC) > 0.5 x 10⁹/L were 12, 15, and 12 days, respectively, and the median times to platelet transfusion independence were 30, 19, and 15 days. Conclusion: PIXY321 can be safely administered and effectively mobilizes PBC in patients with bone marrow defects. PlXY321-mobilized PBC autotransplants result in rapid and sustained hematopoietic recovery.