Primary Appointment

My research interests largely relate to the development of novel transplant regimens, with particular focus on autologous transplantation.

1) With my background training in transplantation and in pharmacology, I have designed, conducted and published phase I trials that have added new promising drugs with an adequate profile to the transplant armamentarium. Examples include dose-escalation trials of docetaxel and gemcitabine. I am presently the PI of clinical trial 2006-0803, which combines infusional gemcitabine with busulfan/melphalan for patients with lymphoid malignancies. This new regimen is showing high activity in patients with refractory lymphomas, most notably Hodgkin's disease. Once its phase II dose is fully defined we intend to test it at a broader level in a multicenter setting, ultimately comparing it to BEAM, which has been the standard HDC regimen over the past two decades with relatively unsatisfactory results for patients with refractory tumors.

I am actively collaborating with Dr Roy Jones in an NCI-sponsored project that will combine the new PARP inhibitor ABT-888 with alkylator-based HDC. We have established collaborations with Drs William Plunkett and Robert Orlowski at MD Anderson, as well as James Doroshow at the NCI for the pharmacodynamic and pharmacokinetic correlative studies that this trial will require. I will pursue funding for this trial  from the NCI through an R21 application, as well as from other sources.

2) In prior NCI- and ACS-funded research projects at the University of Colorado my collaborators and I studied relevant new targets in the setting of autologous transplantion for solid tumors. Examples included the identification of overexpression of HER2 or EGFR, or the presence of high tumor microvessel density as independent adverse predictors of outcome among patients receiving HDC. These observations prompted a novel transplant strategy pursuing selective sensitization of tumor cells to HDC using the appropriate targeted agents. In a joint study at the Universities of Colorado and Duke we first showed the feasibility and high activity of the concurrent combination of trastuzumab with HDC. In further development of this concept I have initiated at MDACC trials combining bevacizumab with a HDC regimen of gemcitabine/docetaxel/melphalan/carboplatin, which was specifically designed for solid tumors. In collaboration with Drs Gershenson, Coleman and other collaborators from Gynecology Oncology, we are actively enrolling patients with relapsed ovarian cancer in trial 2007-0368. A similar trial, 2008-0378, has just been activated for patients with poor-prognosis relapsed germ-cell tumors, with the collaboration of Drs Pagliaro and colleagues from Genitourinary Medical Oncology. This trial will also accrue at the Fred Hutchinson in Seattle, with the participation of Drs Margolin and Holmberg.

3) As a continuation of my long-standing collaboration with Dr Shpall, I am in the process of initiating a trial (2007-0886) testing a novel ex-vivo sequential purging strategy of apheresis products of patients with myeloma who are autologous transplant candidates. This strategy targets both the mature and the undifferentiated ("stem-cell") myeloma populations. It has been approved by the IRB and we are currently working on an IND application to the FDA.

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Last updated: 9/7/2011