I am interested in the development of new agents and treatment approaches for patients with myelodysplastic syndromes and acute myeloid leukemia.
In conjunction with Drs. John DiPersio and Michael Rettig, we are currently conducting a Phase I/II Study of AMD3100 (plerixafor) in combination with mitoxantrone, etoposide and cytarabine for relapsed or refractory AML. AMD3100 is a CXCR4 antagonist currently under clinical development as a stem cell mobilizing agent for use in hematopoietic transplantation. Preclinical evidence suggests that AMD3100 can disrupt the interaction of leukemic blasts with the bone marrow microenvironment sensitizing these cells to genotoxic stresses such as chemotherapy. This trial is designed as a proof of concept study to determine if AMD3100 "priming" can be safely administered and whether it can improve response rates in AML.
We are also conducting a Phase I/II Study of the histone deacetylase inhibitor LBH589 in combination with decitabine in patients age >60 with high risk MDS or AML. Decitabine is a hypomethylating agent that is approved for the treatment of MDS. A recently completed Phase II study led by Dr. Amanda Cashen established the clinical activity in elderly patients with AML. The addition of LBH589 will allow us to evaluate the hypothesis that two epigenetic modifiers that are believed to work through distinct mechanisms of action may act together to improve the responses of patients treated with decitabine alone, without significant additional toxicity.
Finally, we have established a tissue repository for patients undergoing hematopoietic stem cell transplantation. Bone marrow and peripheral blood specimens as well as comprehensive clinical information are being collected on all patients undergoing transplantation in a prospective fashion. This bank will be an invaluable resource to investigate factors which contribute to disease relapse, immunologic reconstitution and graft versus host disease post transplant.