Jason R. Gotlib, MD

The Clinical Investigator Pathway in the Hematology Division at Stanford University Medical Center

The Hematology Fellowship Training Program at Stanford University Medical Center has traditionally consisted of at least a three-year training program in which fellows undergo 14 months of clinical training in both malignant and non-malignant hematology, followed by two years of basic research training under the guidance of a faculty member. The Hematology Division has recognized the requirement for more rigorous training in clinical research and is encouraging more fellows to choose clinical research as a career path. In 1998, the program was split into two research pathways after the period of clinical training. One pathway consists mostly of fellows with substantial research experience who continue to pursue basic research with a principal investigator. The second track, the Clinical Investigator Pathway, allows fellows to obtain formal clinical research training, and to develop and conduct clinical trials under the supervision of faculty.

The Clinical Investigator Pathway: My Story

I joined the Hematology Division as a fellow in July 1998. I was undecided as to whether I would pursue the basic research or clinical investigator track. I had a fair amount of basic research experience, having worked in a lab which investigated the molecular pathogenesis of Alzheimer’s Disease, and in a genetics lab at Stanford in which I studied the genetic basis of growth-related developmental disorders. Still, I was primarily interested in a career that retained contact with patients. In the beginning of 1999, I decided to pursue the Clinical Investigator Pathway, the first fellow to pursue this course. I chose Dr. Peter Greenberg as my mentor, an internationally recognized expert in the study of Myelodysplastic Syndrome (MDS). Stanford University Medical center has a designated MDS Center of Excellence which provides patients with access to special expertise, clinical evaluation, resources, and treatment of their disease through coordinated clinical and laboratory research.

In 1999, during my first year of fellowship, I began formulating ideas with Dr. Greenberg for a specific clinical research project that would serve as the central component of a research grant proposal. I decided to investigate a novel class of small molecule cancer therapeutics termed farnesyltransferase inhibitors (FTIs), which function to inhibit the signaling protein Ras and other proteins in cancer-driven pathways. I wanted to test the hypothesis that FTIs would be effective in chronic myeloproliferative disorders, diseases in which excessive myeloproliferation, often associated with de-regulated Ras, plays a central role in their development.

In order to develop clinical research experience, I became involved with several active clinical research projects, including a phase II study of Amifostine in patients with MDS, and a phase I/II study of the tumor necrosis factor receptor fusion protein (TNFR:Fc, Enbrel) in MDS patients. These experiences provided a useful introduction to numerous aspects of clinical research, including protocol development, patient enrollment and clinical trial care, and data management.

In October 1999, I submitted a ‘K23 Mentored Patient-Oriented Career Development Award’ grant to the NIH. The broad, long-term objective of the research proposal was to investigate novel therapies in the treatment of MDS and Myeloproliferative Disorders (MPDs), with a focus on FTI biology and treatment of MPDs. Although this initial submission did not receive a high enough priority score for funding, I submitted a revised grant for the June 2000 cycle deadline. In January 2001, I was notified that the NIH would grant a 5-year award supporting my clinical research project and training.

A key element of the K23 grant is formal clinical research training. As part of an ongoing effort to develop a cadre of well-trained clinical investigators, the NIH implemented the K30 program. K30 grants are awarded to institutions to support the development of curriculums that teach the methodologic research skills required for high caliber clinical research. After being awarded a K30 grant, Stanford’s Department of Health Research and Policy inaugurated its Master’s degree program in Clinical Epidemiology in the Fall 2000. The core curriculum consists of classes in statistics, epidemiology, design and conduct of clinical trials, responsible conduct of research, research seminars, and completion of a Master’s thesis. Trainees also have the opportunity to take elective courses suited to their research needs. In addition to Dr. Greenberg serving as my clinical research mentor, I have selected a mentor from the core faculty of the Clinical Epidemiology program to assist me through my course of clinical investigation. I commenced the Master’s program in Clinical Epidemiology in September 2000, and plan to complete the program over two years, mixing class time with patient care / clinical trial responsibilities.

Listed below are active or planned protocols with which I have become involved as part of Stanford’s MDS Center. If you would like more information regarding the Clinical Investigator Pathway, the Stanford MDS Center, or the clinical trials listed below, you can reach me at telephone number (650) 723-5007.

• Phase I/II Study of the Farnesyltransferase Inhibitor R115777 in Patients with Myeloproliferative Disorders
• A Phase I Study of ZARNESTRA™ (Farnesyltransferase Inhibitor R115777) and GLEEVEC™ in Adult Patients with Accelerated or Blast Phase Chronic Myelogenous Leukemia (CML) (with Oregon Health & Science University)
• Phase II Study of the Farnesyltransferase Inhibitor R115777 in Previously Untreated High-Risk Myelodysplastic Syndrome and Acute Myelogenous Leukemia (Central site: University of Maryland Cancer Center)
• Safety and Efficacy Study of Bevacizumab: Anti-VEGF Humanized Monoclonal Antibody Therapy for Myelodysplastic Syndrome (MDS) A Randomized, Double-Blind, Placebo-Controlled Trial Comparing Best Supportive Care and Thalidomide (Thalomid® ) for the Treatment of Anemia in Patients with Myelodysplastic Syndrome Followed by Open-Label Treatment with Thalidomide (Multi-center)
• A Pilot Study of Darbepoietin alpha in Patients with Myelodysplastic Syndrome (MDS) (with Vanderbilt University Medical Center)