A new Phase 3 clinical trial at Winship is enrolling participants after extremely encouraging results in the study's first two phases indicate the first-in-class high-precision cell therapy retains the benefits of stem cell transplant without such serious complications as graft versus host disease (GvHD) and disease relapse in patients with certain blood cancers.
Winship is one of several clinical trial sites for the Precision-T study evaluating the safety and efficacy of Orca-T, a cell therapy that combines purified cells from a matched donor, in patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and high-risk myelodysplastic sydromes (MDS). Winship will enroll 20 of the expected 174 total participants in the randomized study.
Leading the study at Winship as the local principal investigator is Edmund K. Waller, MD, PhD, FACP, interim associate director of clinical research and the Rein Saral, MD, Professor in Cancer Medicine at Winship, and professor in the Departments of Medicine, Pathology, and Hematology and Medical Oncology at the Emory University School of Medicine. Waller notes that GvHD is a serious risk for anyone who receives a donor transplant. "GvHD is an immune reaction of donor T cells against normal tissues in the transplant recipient," he says. It can occur in any transplant of blood cells from a donor to a patient and can be very dangerous. "Graft versus host disease can cause severe damage to the skin, liver, intestines and lungs,” Waller says.
Orca-T combines purified cells from a matched donor to replace a patient's diseased blood and immune system with a healthy one while lowering their risk of developing GvHD and other life-threatening transplant-related side effects. To date, nearly 200 patients have been treated with Orca-T with very positive results, recently reported at the European Hematology Association (EHA) 2022 Congress, the 2022 Tandem Meetings |Transplantation & Cellular Therapy Meetings of the American Society of Transplantation and Cellular Therapy (ASTCT) and Center for International Blood and Marrow Transplant Research (CIBMTR), and the American Society of Hematology (ASH) annual meeting.
Orca-T is intended to avoid the significant risks of GvHD and disease relapse associated with standard treatments. To create the precision-engineered donor graft, Waller explains that different cellular subsets in the graft are selectively purified and then infused into the transplant recipient in a timed fashion. First are the bone-marrow-reconstituting stem cells and a population of regulatory T cells. These cells expand and help prevent both rejection of the graft and GvHD.
Two to three days later a small number of conventional T cells are infused. The conventional T cells help eliminate the cancer in the patient through a process called "graft-versus-leukemia." Waller says the net result of giving the patient a precise number of donor T cells with specific functions "leads to better elimination of cancer with less graft versus host disease and less toxicity from the transplant."
According to Ivan Dimov, PhD, cofounder and chief executive officer of Orca Bio, the Menlo Park, Calif.-based biotechnology company behind Orca-T, "The Precision-T study is an important step forward for patients battling deadly blood cancers like AML and ALL, which are often aggressive and for which standard allo-HSCT treatment carries significant risks." Allogeneic HSCT uses human leukocyte antigen (HLA)-matched stem cells derived from a donor. Survival after allogeneic transplantation depends on donor–recipient matching, the graft-versus-host response and the development of a graft versus leukemia effect.
Waller sees great promise in Orca-T and the Precision-T study. "This study indicates that transplantation of defined populations of cells can lead to improved patient outcomes," he says, pointing out that it could also have even wider implications. "The platform technology used in this study can be applied to include additional populations of cells that may further improve survival and decrease complications for patients with leukemia and MDS undergoing allogeneic stem cell transplantation," he says.
The Precision-T study is funded by Orca Bio, a clinical-stage biotechnology company developing purified, high-precision cell therapies for the treatment of cancer, autoimmune diseases and genetic blood disorders.