Joshua Zeidner

MD, Assistant Professor, UNC-Chapel Hill, Clinical Research

Assistant Professor
UNC-Chapel Hill
Clinical Research

Area of interest

My research interests include improving outcomes, drug discovery and development, and designing clinical trials in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs). My research predominantly encompasses drug development in two distinct pathways in AML: 1) cell cycle kinase inhibitors, and 2) innovative immunotherapeutic strategies.

Cell Cycle Kinase Inhibitors:

During my fellowship at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, under the mentorship of Drs. Judy Karp and B. Douglas Smith, I developed a lead role on a multicenter randomized phase 2 study evaluating a novel induction regimen known as FLAM (flavopiridol- a pan cyclin-dependent kinase inhibitor, followed by cytarabine and mitoxantrone) versus 7+3 (cytarabine as a continuous infusion days 1-7, daunorubicin days 1-3) in newly diagnosed AML. 7+3 has been used as a standard induction therapy for newly diagnosed AML patients for the past 4 decades despite suboptimal outcomes. This study enrolled 165 patients from 10 different institutions in 2 years. Ultimately, FLAM was shown to lead to superior remission rates compared to 7+3. This study was presented at the 2012 ASH meeting, the 2013 CTEP Early Drug Development Meeting, and the 2014 ASCO meeting, where I was awarded the 2014 Bradley Stuart Beller Merit Award for the highest ranked abstract submitted by a fellow. The results of this study were published in Haematologica. Given the promising results of this study, I am involved in the further design and implementation of alvocidib (flavopiridol) investigation in AML, where a phase 2 biomarker study is being evaluated to better determine predictors of response to FLAM.

Innovative Immunotherapy Approaches:

More recently, my research has focused on developing innovative immunotherapeutic strategies for AML. The immune system plays a vital role in the pathogenesis and treatment of cancer. Moreover, the immune system is dysfunctional in AML patients before and after commencing chemotherapy. Thus, modulating and targeting the immune system in AML represents a unique therapeutic opportunity to augment anti-leukemic immunity. My immunotherapy interests parcel the targeting of two distinct pathways:

1) T cell populations, such as regulatory T cells (Tregs). In collaboration with Dr. Ivana Gojo at Johns Hopkins, we are evaluating the role of pomalidomide, an immunomodulatory agent (IMiD), after induction chemotherapy in AML patients, as a means to modulate Tregs (the suppressive component of the immune system) and stimulate the immune system. This is a phase 1 dose escalation trial with extensive correlates aimed to assess biologic correlates of response and in vivo immune activity of pomalidomide, marking the first time this agent is investigated in AML. We hypothesize that the inhibition of Tregs by pomalidomide will augment a potent anti-leukemic immune response and lead to a higher remission rate.

2) Co-inhibitory molecules, such as CTLA-4, PD-1, and LAG-3. We are currently evaluating the safety and efficacy of Ipilimumab, a monoclonal antibody targeting CTLA-4, in MDS and AML patients in collaboration with Dr. Doug Smith at Johns Hopkins. We have also shown that PD-1 is a significant immune escape mechanism for leukemic cells, and have thus been interested in exploring anti-PD-1 strategies in AML. I have designed a phase II clinical trial evaluating the safety and activity of pembrolizumab (anti-PD-1) in relapsed/refractory AML patients after high dose cytarabine salvage chemotherapy. With collaboration amongst our Immunotherapy and Bioinformatics groups, we aim to identify potential predictive immune biomarkers of response to pembrolizumab in AML.

With a primary interest of early-phase drug development, I am also the Principal Investigator of multiple clinical trials evaluating novel agents in MDS and AML.

Awards and Honors

2000 Dean’s Scholarship
2002 Golden Key International Honor Society
2004 Magna Cum Laude
2006 American Society for Clinical Pathology Award
2007 Alpha Omega Alpha Medical Honor Society
2007 Selected Participant for Ninth Annual American College of Physicians Board Review
2008 Department of Medicine Academic Award
2012 Samuel Smith Leukemia Fellowship Award
2012 Selected Participant in AACR/ASCO Methods in Clinical Cancer Research Workshop, Vail, CO
2012 American Society of Hematology (ASH) Abstract Achievement Award for 2012 ASH Conference, Atlanta, GA
2013 ASCO Conquer Cancer Foundation Young Investigator Award, In memory of John R. Durant, MD
2013 Recipient of National Institute of Health (NIH) Loan Repayment Program
2014 Bradley Stuart Beller Merit Award- awarded top abstract submitted by fellow to 2014 ASCO Conference
2014 Leukemia and Lymphoma Society Special Fellow in Clinical Research
2016 Junior Faculty Development Award

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