A new Phase I-II clinical trial sponsored by Kite Pharma, Inc. hopes to show an effective way to treat refractory aggressive non-Hodgkin lymphoma from within. The study utilizes investigational CAR (chimeric antigen receptor) T-cells, which have been genetically modified to recognize cancer and mount an immune response.
“Over the last few years, CAR T-cell therapy has emerged as a novel approach, designed to more effectively target blood cancer at the cellular level,” said Ian Flinn, MD, PhD, medical director of the Sarah Cannon Center for Blood Cancer at TriStar Centennial.
Currently recruiting patients, the multi-center clinical trial is being conducted at both Sarah Cannon Center for Blood Cancer at TriStar Centennial and at Vanderbilt-Ingram Cancer Center. The two Nashville investigational sites are among the handful of prestigious centers nationwide – including MD Anderson, Cleveland Clinic, Dana-Farber Cancer Institute, and Moffitt Cancer Center – participating in this trial to determine the safety and efficacy of the immunotherapy in a larger population of patients.
“This trial is the first in a series that we’re opening with this type of therapy. This particular trial is for patients with refractory diffuse large B-cell lymphoma (DLBCL),” said Flinn, who serves as principal investigator for the trial at Sarah Cannon. He added the therapy would also be applied to other hematologic cancers going forward.
This initial trial is open to DLBCL patients who have already undergone standard therapy and either failed to get the desired response through cytotoxic chemotherapy or who have now relapsed. This immunotherapy trial evaluates the efficacy of KTE-C19 to harness the body’s own immune system in fighting the disease.
Flinn explained researchers will harvest a patient’s lymphocytes that will then be genetically modified to insert a CD19 receptor targeting the lymphoma. Once the patient’s own T-cells are modified, the engineered cells will be infused into the patient’s blood stream.
“Part of the cell modification is the activation of the T-cells,” he continued. “It acts like a light switch for the T-cells … turning them on and saying, ‘Go fight the foreign object, which in this case, is the lymphoma.”
The modified lymphocytes specifically look for anything that expresses CD19, which is a biomarker for B cells. “Lymphoma is a cancer of the immune system,” Flinn said, adding that most lymphomas are B cell malignancies that express CD19 on their surface, making them ideal targets for the engineered cells.
“There are also normal cells that express CD19 so a concern is that if this is 100 percent effective, it might disrupt the production of normal B cells, as well,” he continued.
However, Flinn said he isn’t overly concerned about this particular unintended consequence because antibodies targeting the similar CD20 in B cells have been in use for years. “There were many concerns when we started treating people with Rituxan® in the late 90s that it would make people profoundly immunodeficient, but thankfully, that has only been seen in a very small percentage of the population.” He added patients who do become severely immunosuppressed would be treated with immunoglobin to combat the immunosupression and the research team is trained to closely monitoring for that specific situation.
The hope, as with any clinical trial, is that the benefits will far outweigh any negative side effects. Although not easy, the process is generally no more cumbersome for patients than a stem cell transplant that is often used as a second line of defense for many hematologic malignancies, and there is no maintenance protocol with this new therapy.
After the cells are harvested by apheresis and genetically modified, the activated cells are returned to the trial center and stored while patients are given chemotherapy on an outpatient basis. The patients are then admitted, infused with the CAR T-cells, and remain hospitalized for seven days for observation. If there are no appreciable side effects, patients will be discharged home, returning to the clinic for periodic evaluation.
At the American Society of Hematology meeting in December 2015, data from the University of Pennsylvania was presented on a related therapy that showed a portion of patients who were not responding to any other treatments went into a durable, long remission from this type of approach, with some from that group continuing to remain in remission.
“As oncologists, we always search for answers for those who have failed conventional therapies,” said Flinn. “The hope is that this therapy will ultimately not only serve patients in a relapse setting but can be used as an earlier therapy for patients who are at high risk of relapse. I think the immediate goal of this trial is to get people into remission and have long-lasting remissions.”
The great news, he concluded, is there have been a tremendous number of new therapies emerging for hematologic cancers. “There’s been a wave of very targeted treatments,” he noted, adding this exciting approach has the potential to significantly add to the armamentarium.
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