SEATTLE – July 27, 2017 – After seeing promising results in phase 1 of the Pediatric Leukemia Adoptive Therapy (PLAT-02) trial with 93 percent of patients with relapsed or refractory acute lymphoblastic leukemia (ALL) achieving complete initial remission, researchers at Seattle Children's are continuing their quest to improve the experimental therapy and reduce the rate of relapse, which is about 50 percent. Researchers have now opened a phase 1 clinical trial, PLAT-04, for children and young adults with relapsed or refractory CD22-positive ALL. They will examine the safety and feasibility of administering cancer-fighting chimeric antigen receptor (CAR) T cells that have been reprogrammed to target the CD22 protein expressed by some leukemia cells.
"We're at a pivotal point where we're building upon what we've learned in the PLAT-02 trial and opening new trials, like PLAT-04, with the goal of improving this therapy to the point that it becomes a long-term cure for all of our leukemia patients," said Dr. Corinne Summers, an oncologist at Seattle Children's and the lead investigator of the PLAT-04 trial.
Summers and the research team, led by Dr. Mike Jensen at the Ben Towne Center for Childhood Cancer Research at Seattle Children's Research Institute, are opening PLAT-04 after discovering that of the patients who relapsed in the PLAT-02 trial, approximately 40 percent of them relapsed with a leukemia that evolved to circumvent the CAR T cells that were reprogrammed to detect and destroy cancer.
In PLAT-02, the CAR T cells are reprogrammed to recognize and target the CD19 protein that is expressed by most precursor B acute lymphoblastic leukemia cells. However, in some patients, the leukemia recurred without the CD19 target and expressed a protein that the CAR T cells were unable to recognize — CD22. With the PLAT-04 trial, researchers will now be able to reprogram CAR T cells to detect and destroy leukemia cells that express the CD22 protein. Researchers hope to enroll more than 30 patients in the trial over the next two to three years.
"Leukemia cells evolve in order to find ways to survive," said Summers. "For the patients who relapse with CD22-positive leukemia, we are very pleased to now be able to offer a treatment option that will hopefully lead them to finally achieving long-term remission."
The PLAT-04 trial follows the PLAT-03 trial that Seattle Children's opened in May. PLAT-03 institutes another strategy aimed at increasing long-term remission — introducing T-cell "boosters" intended to improve the persistence of CAR T cells. Researchers are also working to develop a trial where they will reprogram CAR T cells to identify the CD19 and CD22 proteins simultaneously, enabling them to target the cancer cells from more than one angle with the initial round of T-cell immunotherapy.
"We believe T-cell immunotherapy has tremendous potential," said Summers. "This is why we're diligently working to employ several strategies that we hope will lead us to reaching our ultimate goal of developing the best therapy possible — a therapy that can be given to patients as a first line of defense, greatly reducing the side effects of cancer treatment and leading to a cure."
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The T-cell immunotherapy trials at Seattle Children's are funded in part by Strong Against Cancer, a national philanthropic initiative with worldwide implications for potentially curing childhood cancers. If you are interested in supporting the advancement of immunotherapy and cancer research, please visit Strong Against Cancer's donation page.
For more information on immunotherapy research trials at Seattle Children's, please call (206) 987-2106 or email [email protected].
About Seattle Children's
Seattle Children's mission is to provide hope, care and cures to help every child live the healthiest and most fulfilling life possible. Together, Seattle Children's Hospital, Research Institute and Foundation deliver superior patient care, identify new discoveries and treatments through pediatric research, and raise funds to create better futures for patients.
Ranked as one of the top children's hospitals in the country by U.S. News & World Report, Seattle Children's serves as the pediatric and adolescent academic medical center for Washington, Alaska, Montana and Idaho – the largest region of any children's hospital in the country. As one of the nation's top five pediatric research centers, Seattle Children's Research Institute is internationally recognized for its work in neurosciences, immunology, cancer, infectious disease, injury prevention and much more. Seattle Children's Hospital and Research Foundation works with the Seattle Children's Guild Association, the largest all-volunteer fundraising network for any hospital in the country, to gather community support and raise funds for uncompensated care and research.
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