A randomized controlled trial comparing the efficacy of Eltrombopag plus Filgrastim versus Filgrastim alone for peripheral blood stem cell mobilization in patients undergoing autologous stem cell transplant for lymphoma

Background:

Over the past decade, different strategies have been implemented to achieve adequate apheresis yields for successful engraftment during autologous transplant. However poor mobilization is seen in 10% of patients. While chemotherapy induced mobilization and addition of plerixafor has helped in reducing mobilization failure, both options are still very costly. Eltrombopag is an orally bioavailable small molecule thrombopoietin receptor (TPO-R) agonist approved by the FDA for treatment of chronic immune thrombocytopenic purpura (ITP), Aplastic Anemia and Chronic Hepatitis C. In vitro studies have demonstrated that Eltrombopag promotes megakaryocyte proliferation and differentiation of CD34+ bone marrow progenitor cells, suggesting that Eltrombopag might be a surrogate for rhTPO for stem cell mobilization. In this trial, we plan to evaluate the combination of Eltrombopag plus standard G-CSF for stem cell mobilization in patients with Lymphoma, for which ASCT is indicated.

Methodology: This is aphase II, open-label, randomized control trial, comparing the efficacy of combining Eltrompbopag with G-CSF for peripheral blood stem cell mobilization in patients with Lymphoma undergoing Autologous transplant. Patients will be randomized to receive either G-CSF alone [5 ug/kg BD] for 4 days or G-CSF [5 ug/kg BD for 4 days] in combination with Eltrombopag 150 mg OD for 7 days. The primary objective will be to determine the number of patients who achieve a cell dose of 5 x 106/kg CD34+ cells on the first apheresis day. Inclusion criteria will be patients with Lymphoma in remission or with stable disease after salvage chemotherapy with indication for stem cell mobilization and ASCT. A total of 100 patients will be enrolled - 50 in each arm. If patients do not achieve the target cell dose on the first day, physicians will be free to use plerixafor for the second mobilization. Inj. Plerixafor at 0.25mg/kg can be administered 12 hours prior to the second day harvest. All patients will be monitored for adverse events (AEs) and they will be graded by NCI-CTCAE v4.

Results: The primary efficacy endpoint will be the proportion of patients obtaining > 5 x 106/kg CD34+ cells on the first apheresis day.The secondary endpoints will include the median days required for neutrophil and platelet engraftment, the need for plerixafor use and a second harvest, the total packed red cell and platelet transfusion required during the peri-transplant period, from the initiation of mobilization till the time of engraftment.

Conclusions: We hope to show that addition of Eltrombopag to G-CSF will achieve adequate apheresis yields for successful stem cell mobilization in these patients.