OSUCCC-James Oncologists Share Ongoing Research Efforts in Hematologic Malignancies

At the 2019 OncLive^® State of the Science Summit™ on Hematologic Malignancies, experts from The Ohio State University Comprehensive Cancer Center (OSUCCC)—James highlighted exciting research being conducted at their institution.

Narendranath Epperla, MD, MS

Narendranath Epperla, MD, MS

Hematologist at The OSUCCC—James

“We do have a lot of Hodgkin lymphoma trials, both in the frontline and relapsed/refractory settings. We have a SWOG study that is utilizing the nivolumab (Opdivo) combinations in the relapsed/refractory setting. We have nivolumab with lenalidomide (Revlimid), nivolumab with ibrutinib (Imbruvica), and brentuximab vedotin (Adcetris) with ibrutinib. A new trial will be opening up that is [examining] gemcitabine, bendamustine, and nivolumab. There are definitely a lot of options in the relapsed/refractory setting, and even in the frontline setting with combinations of novel agents.

In the follicular lymphoma realm, we also have a phase I study that was presented at the 2019 ASH Annual Meeting, [which examined] the combination of obinutuzumab (Gazyva), lenalidomide, and venetoclax (Venclexta) in relapsed/refractory non-Hodgkin lymphoma that showed very good safety data and is currently on hold for data analysis. However, it will eventually open for an expansion cohort. In mantle cell lymphoma, we have a slew of clinical trials both in the frontline and relapsed/refractory settings.”

Jonathan Brammer, MD

Jonathan Brammer, MD

Assistant Professor and Hematologist at The OSUCCC—James

“Currently, one of my clinical trials is specifically designed for patients with T-cell malignancies, including T-cell acute lymphoblastic leukemia (ALL), and other T-cell leukemias—more rare diseases, such as T-cell prolymphocytic leukemia or peripheral T-cell lymphoma.

One trial is using some other drugs in combination with standard conditioning chemotherapy, followed by a maintenance therapy in an effort to eradicate the disease. We know that patients with T-cell ALL are at very high risk of relapse, even after they have received stem cell transplant. This clinical trial is currently the only one in the United States, and probably worldwide, that is specifically looking at evaluating T-cell malignancies and T-cell leukemias using allogeneic stem cell transplant.

We also have another clinical trial for patients with T-cell [malignancies] who have relapsed. This trial combines a novel drug called BL-8040, which targets a specific protein on the cancer cells, with standard chemotherapy at the relapse of T-cell ALL. This combination is available for patients who have relapsed after their initial treatment for ALL.”

Maria Chaudhry, MBBS

Maria Chaudhry, MBBS

Hematologist at The OSUCCC—James

“We participate in clinical trials because as a researcher, I’m interested in development. Therefore, we have a few early-phase clinical trials that are open. [There is an] immunotherapy drug, which is an IgG4 monoclonal antibody that targets CD38. This is still in phase I, early stages of development, but we have seen promising results.”

Jennifer Woyach, MD

Jennifer Woyach, MD

Associate Professor in the Department of Internal Medicine at The OSUCCC—James

“We have many clinical trials being done in chronic lymphocytic leukemia (CLL), as well as some really interesting laboratory work. In terms of clinical trials, we do have the successor [US] Cooperative Group studies open: EA9161 (NCT03701282) and A041702 (NCT03737981).

Both of these studies are for frontline CLL—again dividing patients up by age—and are comparing ibrutinib/obinutuzumab with ibrutinib/venetoclax/obinutuzumab. There are plans for discontinuation of treatment in patients who go on to receive triplet therapy. Those trials are really exciting and are open at many different places.

We also have studies in the frontline setting of ibrutinib in combination with daratumumab (Darzalex), which is a CD38-directed antibody. The idea there is that we are impacting the CLL tumor microenvironment, which by and large expresses CD38, as well as the CLL cells with ibrutinib. We are hoping that by doing this, we are hitting the disease from 2 different areas, like the microenvironment and the cells themselves.

In the relapsed/refractory setting, there are some combinations that we’re examining—a few in industry settings and some with other institutions, such as the umbralisib/ublituximab/venetoclax study that TG Therapeutics, Inc., is running. We also have clinical trials examining ARQ 531 and the LOXO-305, which are 2 reversible BTK inhibitors.

We just opened a couple of new studies that are really interesting. One is a study with a new bispecific antibody by Xencor; this is a CD3- and CD20-targeting bispecific antibody. The second just opened; it’s a study looking at tumor-infiltrating lymphocytes. In this trial, we are taking peripheral blood T cells and expanding them in the laboratory—there is no modification done to them, they’re just expanded—with the idea that among all T cells in a patient with CLL, some will actually have potential to react against the CLL itself.

Patients are then given lymphodepleting chemotherapy and [we put] those T cells put back into them, in combination with interleukin-2, to further activate those tumor-specific T cells. I believe that’s a really exciting approach; it’s just a little bit different than CAR T cells and it would not preclude someone from getting CAR T cells in the future. However, [this approach] may be an interesting way to move forward in CLL—something that [is already] being done in solid tumors.”