Hematology and Oncology Research
Building a robust clinical and laboratory research program is a primary mission of the Division of Hematology and Oncology. Under the leadership of Dr. Parameswaran Hari, Division Chief, Drs. Ehab Atallah, James Thomas, and Joshua Field, Section Heads of Hematologic Malignancies, Solid Tumor Oncology, and Benign Hematology, respectively and Dr. Mehdi Hamadani, Director of Blood and Marrow Transplant (BMT) and Cellular Therapy Program, the Division has been successful in creating a climate conducive to clinical research and to developing high-quality, nationally recognized research programs. The CIBMTR (Center for International Blood and Marrow Transplant Research) led by Dr. Bronwen Shaw, Chief Scientific Director, pioneers hematopoietic cell transplantation and cellular therapies. Our basic science laboratory program has made significant contributions to our understanding of graft vs. host disease, immune oncology, multiple myeloma and other cancers.
Professor; Section Chief Benign Hematology; Medical Director Adult Sickle Cell Program
Professor of Internal Medicine
Professor; Scientific Director CIBMTR
Clinical Research Programs
The Medical College of Wisconsin is a leading program advancing novel forms of cell therapy and chimeric antigen receptor (CAR) modified T-cells through innovative clinical trials. Embracing cutting edge technologies, MCW has invested in the Prodigy CliniMACS® which is a completely closed processing system allowing point of care manufacturing of CAR T-cells within our dedicated cell therapy suite. Using this technology, Dr. Nirav Shah (Associate Professor of Medicine) and Dr. Parameswaran Hari (Professor of Medicine & Division Chief of Hematology/Oncology) in 2017 launched a first-in-human single-center bispecific anti-CD20, anti-CD19 CAR T-cell (CAR20.19) trial for non-Hodgkin Lymphoma (NHL). Exciting results from this initial study published in Nature Medicine have led to the rapid development of multiple targeted studies using this same product for different indications. These include a CAR20.19 pediatric ALL study in collaboration with Dr. Julie Talano of the Children’s Hospital of Wisconsin and a rapid manufacturing CAR20.19 trial in NHL led by Dr. Nirav Shah. Most recently, Dr. Shah and colleagues from across the United States have recently launched a multicenter Phase II clinical trial to determine the efficacy of CAR20.19 cells for relapsed Diffuse Large B-cell Lymphoma (DLBCL).
In addition to the innovative development of dual targeted CARs, MCW is a collaborator with multiple pharmaceutical companies bringing innovative cellular therapies to patients in southeastern Wisconsin. Our BMT and cell therapy program has established several trials utilizing allogeneic CAR T-cell products, novel manufacturing platforms, and combinatorial oral agent with CAR products that are already available to patients joining clinical trials. While the majority of cell therapy programs are limited to hematological malignancies, MCW has recently participated in several trials using T-cell Receptor (TCR) technologies for difficult to treat solid malignancies. Together, MCW aims to continue is nationwide leadership in the development to cell therapy for the treatment of malignancies.
The Medical College of Wisconsin is also one of the leading centers worldwide for research into cellular therapy and blood and marrow transplantation. MCW is home to the Center for International Blood and Marrow Transplant Research (CIBMTR). The CIBMTR maintains a large outcomes database, collecting patient, disease, and transplant data including longitudinal outcomes on allogeneic and autologous transplants and cellular therapies worldwide.
The CIBMTR was formed in 2004 and brought together two major organizations in the field of blood and marrow transplant research: the National Marrow Donor Program® and the Medical College of Wisconsin's International Bone Marrow Transplant Registry (IBMTR; established in 1972) and Autologous Blood and Marrow Transplant Registry (ABMTR). Dr. Bronwen Shaw is the Chief Scientific Director of CIBMTR, MCW and a practicing transplant physician within the MCW BMT program.
MCW faculty serve as leaders within CIBMTR and as the PIs for several large grants or contracts which support and promote the work of the CIBMTR as a premier research organization and a resource to the community.
Dr. Mary M. Horowitz, leads the Data Coordinating Center for the NIH-funded Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Established in October 2001 BMT CTN conducts multi-institutional phase II and phase III clinical trials in the field of hematopoietic cell transplantation. These trials address cutting edge issues in hematopoietic stem cell transplantation (HCT) and cellular therapy, increasing the understanding of treatment approaches as well as developing novel ideas in the field. Dr. Horowitz holds the Robert A. Uihlein Jr Chair in Hematologic Research, is the Chief Scientific Director, Emeritus, CIBMTR and is a practicing transplant physician within the MCW BMT program.
Dr. J. Douglas Rizzo, a practicing transplant physician within the Froedtert and MCW BMT program and the Froedtert & the Medical College of Wisconsin Cancer Service Line Director, leads the Stem Cell Therapeutic Outcomes Database (SCTOD) for the C.W. Bill Young Cell Transplantation Program (administered by the United States Health Resources and Services Administration (HRSA).
Dr. Mary Eapen is a practicing transplant physician within the MCW BMT program and leads (with Dr. Horowitz) a Clinical Trials Infrastructure program for phase I and phase II gene therapy and gene editing trials for sickle cell disease. This is funded by the National Heart Lung and Blood Institute’s Cure Sickle Cell Initiative.
Dr Marcelo Pasquini is the PI for the Cellular Immunotherapy Data Resource. This grant was awarded under the moonshot initiative, part of IOTN, and supports collection of cell therapy data to fulfill the FDA requirement of 15 years of follow up for many of the patients receiving CAR-T cells and other cellular therapies. Dr. Marcelo Pasquini is a practicing transplant physician within the MCW BMT program.
Dr Kathryn Flynn is the senior scientific director for Patient-Reported Outcomes and has been instrumental in adding this important aspect of data to the CIBMTR registry. She is the PI or multiple PI on a number of cross-departmental patient-centered research studies at MCW that use patient-reported outcome measures and/or qualitative methods.
In the hematological malignancy and cellular therapy group we strive to not only provide the best patient care but also advance and improve the treatment for patients with hematological malignancies. Many of our faculty are leading or involved in cutting edge research to improve the outcome of our patients. Several of our faculty are leading studies in the NCI funded myeloMATCH initiative. The goal of the Myeloid Malignancies Molecular Analysis for Therapy Choice (myeloMATCH) initiative is to optimize therapeutic strategies for adult and young adult and adolescent patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). An initiative of the National Cancer Institute (NCI) and the NCI-supported National Clinical Trials Network (NCTN) Groups, myeloMATCH programmatically links the AML/MDS trials of the NCTN Network Groups, with the aim of more precisely targeting disease as a patient proceeds through successive clinical trials. The Medical College of Wisconsin is the administrative core site for the H Jean Khoury Cure CML consortium (HJKC3). The HJKC3 is a group of researchers from 19 world-class academic medical centers throughout North America committed to curing chronic myeloid leukemia (CML) through innovative research. With feedback from advocates and patients, the HJKC3 strives to meet the needs of the CML community. Our team has also been involved in several large research studies evaluating the role of newer therapies in patients with acute lymphoblastic leukemia and are studying new immunotherapies to improve the outcomes of those patients with CAR-T cell therapy or bispecific antibodies. Finally in chronic lymphocytic leukemia, we have participated in several large studies which have led to FDA approval of multiple drugs and led to a marked improvement of patient outcomes.
The MCW Myeloma Clinical program is built on the foundation of providing superlative patient care. Our hematologist/oncologists are experts in this disease and lead multiple research initiatives to improve outcomes of patients. By focusing our efforts on cutting-edge science using novel therapy, clinical trials especially on immunotherapies in multiple myeloma, as well as correlative science, we provide access to patients to new and innovative advances in our field. The long-term goal of the clinical program is to collaborate with MCW William G. Schuett, Jr., Multiple Myeloma Research Laboratory and establish a successful bench-to-bedside-and-back strategy to translate laboratory advances toward curing multiple myeloma.
Leveraging our strength in blood and marrow transplantation and cellular therapies, we have pioneered several clinical trials in myeloma involving transplantation and post-transplant therapies. Most notably, the MCW myeloma program led clinical trials in myeloma through the BMT CTN (Blood and Marrow Transplantation Clinical Trials Network) that entrenched the role of post-transplant maintenance and explored tumor-vaccination approaches in myeloma. Currently, we have a large portfolio of novel immunotherapeutic clinical trials including a portfolio of bispecific antibodies and CAR-T cells in relapsed myeloma. Our in-house CAR-T manufacturing capability, one of just a handful in the country, is evaluating a variety of dual targeted and armored CAR approaches in translational efforts to overcome the problem of relapse after currently available CAR-T therapies. Investigators in the program are working on an ongoing clinical trial investigating adoptive T cell transfer of autologous rapamycin- and apoptosis-resistant T cells that can mediate more potent immune reactivity against myeloma. Our unique strength in allogeneic transplantation for high-risk myeloma and plasma cell leukemia has led to other trials involving post allotransplant maintenance and NK cell transfer after haploidentical transplantation. We are currently exploring novel ways to monitor myeloma response using peripheral blood for minimal residual disease measurement.
Our clinical light chain (AL) amyloidosis program is the largest in the state of Wisconsin providing access to clinical trials for patients with newly diagnosed and relapsed AL amyloidosis. Current research initiatives include fibril degradation strategies, novel imaging studies, and quality of life measurement. Myeloma clinical researchers at MCW collaborate with colleagues in other areas and aim to study and improve areas of the patient experience that are rarely studied including stress, anxiety and sleep disturbances. By working with and contributing to various national and international collaboratives (CIBMTR, IMWG and cooperative groups) we aim to advance care for patients worldwide.
The Medical College of Wisconsin (MCW) Pancreatic Cancer Program was first established in 2009 and was recently endowed as the Mary Ann & Charles LaBahn Pancreatic Cancer Program (MCW-LPCP) in 2020. The program is under the direction and leadership of Susan Tsai, MD, MHS, Professor of Surgery. Comprised of over 50 members, the program includes an integrated multidisciplinary team including surgeons, medical oncologists, pathologists, radiation oncologists, diagnostic radiologists, advanced gastroenterologists, palliative care physicians, and basic scientists.
Designated as a National Pancreas Center of Excellence, the MCW-LPCP is the highest volume referral center for pancreatic cancer in Wisconsin and is among the highest volume pancreatic surgery centers in the nation. On average, clinicians see over 100 patients with operable pancreatic cancer each year and perform 80-100 pancreatectomies annually. The program has less than a 1% mortality rate after surgery and is consistently rated as a top performing program nationally. Moreover, approximately 200-350 metastatic pancreatic cancer patients are seen per year. The mission of the program is to deliver comprehensive and compassionate, research driven, patient care rooted in pioneering research discoveries and innovative clinical trials. As a leading institution in early detection, the MCW-LPCP includes a comprehensive high-risk screening clinic (Greater Midwest Pancreatic Cancer Screening Clinic) for patients that are at an increased risk for developing pancreatic cancer. The goal is to identify cancer at the earliest possible stage and have the best chance for positive outcomes.
The MCW-LPCP is part of the larger MCW Cancer Center; shared resources consist of a Scientific Review Committee, Data Safety Monitor Committee, Phase I Clinical Trials Program, Adult Translational Research Unit, and a Clinical Trials Office (CTO) that provides regulatory oversight, funding administration and disease-based research support staff. Within the CTO, there is a dedicated gastrointestinal unit with its own pancreatic cancer clinical trial coordinator. Weekly clinical trial meetings are held to oversee current trial operations and review active trial patients with localized pancreatic cancer. With this robust organization, the MCW-LPCP has led the way in investigator-initiated clinical trials, using precision medicine and biomarker-driven adaptive trial design. Over 60% of patients with operable pancreatic cancer are enrolled in clinical trials.
The MCW-LPCP has a pioneered in integrative research infrastructure for translational science, which includes a longitudinal, clinically annotated biorepository established in 2010 and consists of tissue and blood specimens. To date, the tissue bank staff consented 3,000 patients and collected over 10,000 tissue specimens and 8,000 blood samples. A unique contributor to the biorepository is the Rapid Autopsy Program for Pancreatic Cancer, which supplies tumors and adjacent normal tissue from recently deceased patients. The corresponding clinical database centralizes storage of patient data and has variables such as demographics, lab results, treatment regime, and outcomes. The biorepository is a key feature of the program and drives research initiatives from early detection biomarkers and drug optimization to disease progression studies. Derivatives from surgical specimens are created including cell lines, xenografts, and organoids.