A randomized phase II study of BB-10010:: a variant of human macrophage inflammatory protein-1α for patients receiving high-dose etoposide and cyclophosphamide for malignant lymphoma and breast cancer

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is a chemokine that can inhibit the cell cycle progression of both primitive haemopoietic and epidermal progenitor cells. This property could potentially be exploited to attenuate both the myelosuppressive effects of chemotherapy as well as mucositis. We evaluated both the biological and clinical effects of BE-10010, a genetically engineered variant of MTP-1 alpha, in patients with malignant lymphoma or breast cancer receiving high-dose etoposide (VP 3.6 g/m(2)) and cyclophosphamide (Cy 200 mg/kg). 52 patients were randomized to one of three cohorts. Cohort A received no BE-10010; cohorts B and C received 10 mu g/kg and 100 mu g/kg of BB-10010, respectively. All patients received post-chemotherapy G-CSF. BB-10010 was well tolerated. There were no significant differences between groups in recovery to an ANC > 0.5 x 10(9)/l, 1 x 10(9)/l or 1.5 x 10(9)/l, the number of days with an ANC < 0.5 x 10(9)/l, days to a platelet count > 50 x 10(9)/l or 100 x 10(9)/l, or the incidence and severity of mucositis. There was no evidence of any effect of BB-10010 on colony-forming cell (CFC) or long-term culture-initiating cell (LTC-IC) mobilization, cycling activity in the marrow or on chemotherapy-induced changes in CFC or LTC-IC number both of which were in the normal range by 22 d after completion of the chemotherapy. To our knowledge this is the first report of a myelointensive regimen having no apparent long-term effect on the LTC-IC compartment. In summary, BE-10010 is safe when used in patients receiving high-dose therapy but has no effect on reducing the toxicity of such therapy.