Research

Division of Hematology & Oncology
RESEARCH

Division faculty conduct basic, translational and clinical research in partnership with colleagues in the UVA Cancer Center as well as many basic science and clinical departments, which provides access to a remarkable breadth of resources and depth of multidisciplinary expertise.

Areas of clinical investigation include:

Solid tumor oncology
Hematopoietic stem cell transplant
Malignant hematology
Phase I and Phase II clinical trials to advance new treatment approaches, including monoclonal antibodies, vaccines and novel targeted therapies

With the recruitment of a number of outstanding clinical investigators over the past two years, the portfolio of clinical trials is expanding rapidly. These trials bring important new therapeutics to patients, including targeted oral anticancer drugs and immunotherapeutics that offer hope for those with disease poorly responsive to traditional therapies. The division’s clinical research also supports the UVA Health System’s institutional priority on enhancing the regional and national reputation of its cancer programs.

Thomas P. Loughran Jr., MD, director of the UVA Cancer Center, is leading a research program in acute myeloid leukemia supported by a P01 grant that includes nanotechnology-delivered therapeutics. He has additional NCI R01 support in large granular lymphocyte leukemia (a disease entity he discovered more than 20 years ago). As UVA Cancer Center director, he is responsible for the competing renewal of UVA’s NCI Clinical Cancer Center support grant in 2016, and the subsequent goal of achieving NCI Comprehensive Cancer Center status within five years.

ORIEN Initiative

UVA is among the first U.S. cancer centers invited to join the Oncology Research Information Exchange Network (ORIEN), a national network linking patient tumor samples with clinical outcomes data that aims to develop “personalized” treatments targeting specific mutation profiles for individual patients. This is a major new effort in precision medicine, and positions UVA Cancer Center and the division at the cutting edge of important new technology and innovation. More.

See the Publications page for a broader view of division research productivity during the past year.

PI: Craig Portell, MD

Multi-institution Phase I/Ib study of ibrutinib with ABT-199 in relapsed/refractory mantle cell lymphoma
(Supported in part by two-year grant from the Lymphoma Research Foundation’s Clinical Research Mentoring Program.)

Mantle cell lymphoma is not cured by immune-chemotherapy alone, although recent advances have increased the time to progression and overall survival. Ibrutinib, an FDA-approved BTK inhibitor has an overall response rate of 68 percent, but only 21 percent have a complete response and some patients develop very rapidly progressive disease at relapse. Combination regimens that incorporate ibrutinib may improve this outcome.

Preclinical and translational work at UVA found that the combination of ibrutinib with ABT-199 (venetoclax, a selective BCL-2 inhibitor) are synergistic (see publications list). This Phase I/Ib clinical study will evaluate the combination of ibrutinib and ABT-199 in relapsed or refractory mantle cell lymphoma with 6 total dosing cohorts via a continual re-assessment model. Patients will be enrolled in two phases. First, subsequent patients will be enrolled on each dosing cohort. Second, patients will be allocated to the cohort that the model predicts is safe and effective (using response rate at two months on study) based on previously treated patients.

The primary objectives of this study are dose-finding and safety. Secondary outcomes are response rate and survival. Exploratory analyses will identify molecular profiles of patients who progress and molecular attributes, which would predict for success with the combination.

PI: Osama Rahma, MD

Randomized, multicenter phase Ib/II study to assess the safety and the immunological effect of neoadjuvant chemoradiation therapy (CRT) in combination with pembrolizumab (anti-PD-1) compared to CRT alone in patients with resectable or borderline resectable pancreatic cancer

This is a prospective randomized trial that will accrue subjects with pancreatic cancer to assess the safety and immunological effect of the combination of neoadjuvant treatment with pembrolizumab and concurrent chemoradiation (CRT) compared to CRT treatment alone.

Primary objectives: (1) To determine the safety of neoadjuvant CRT in combination with MK-3475 for the treatment of resectable or borderline resectable pancreatic cancer. (2) To estimate the difference in the number of tumor infiltrating lymphocytes (TILs) in resectable or borderline resectable pancreatic cancer subjects receiving neoadjuvant CRT in combination with MK-3475 to the number of TILs in resectable or borderline resectable pancreatic cancer subjects receiving neoadjuvant CRT alone.

PI: Patrick Dillon, MD

Focused ultrasound therapy to augment antigen presentation and immune-specificity of checkpoint inhibitor therapy with indoximod for metastatic breast cancer

The project builds upon preclinical work from UVA suggesting that focused ultrasound may induce controlled apoptotic cell death and antigen presentation and therefore act like an autologous vaccine. Since vaccines alone have been marginally effective at eliciting immune responses, the team seeks to combine focused ultrasound therapy with a safe and tolerable immune adjuvant. Building upon their existing experience with Indoximod — a tryptophan mimetic that augments T cell activation and survival, while inhibiting the development of FOXP3+ T regulatory cells — the team developed a combined therapy approach that will carefully assess clinical and immunologic activity of this novel combination therapy.

The primary endpoints for the ultrasound plus Indoximod clinical trial include the assessment of the safety of the combination in patients with advanced breast cancer and an assessment of the local immune response to the combination by measuring lymphocyte and MDSC infiltrates in advanced breast tumors. Their secondary and exploratory endpoints include assessments of responses at distant sites, assessments of circulating immune responses, local ablation site immune responses, biomarker assessments, and T cell specificity studies.