Clinical research at the Froedtert & the Medical College of Wisconsin health network — anchored by Froedtert Hospital, eastern Wisconsin’s only academic medical center — opens the door to personalized treatment options that offer extensive expertise, resources and innovation and give you access to the highest level of care.
A phase II clinical trial, available only through the Froedtert & the Medical College of Wisconsin Cancer Network, is testing a two-drug regimen to determine if it is more effective than standard drugs in preventing graft versus host disease (GVHD) and stopping it from recurring. Participants are ages 60 and older as GVHD is more often fatal in older adults. The trial is also evaluating the drug combination’s safety.
“Two forms of GVHD occur after allogeneic stem cell transplants,” said Sameem Abedin, MD, medical oncologist, MCW faculty member and principal investigator of the trial. “Acute GVHD affects 30% to 40% of patients after transplant and is life threatening 10% of the time. Chronic GVHD occurs in 50% of patients. It can be disabling and sometimes fatal.”
Acute GVHD typically appears one to three months after the transplant. The chronic form can occur anywhere between three months and 10 years. Patients can live with the chronic form but face quality-of-life symptoms like skin discoloration or tightness, joint stiffness and chronic shortness of breath.
“Since the 1990s, two medications have been the backbone of care — tacrolimus and methotrexate,” Dr. Abedin said. “During the last four years, the Froedtert & MCW Cancer Network participated in a national phase III clinical trial called BMT CTN 1703, which tested adding another chemotherapy drug, cyclophosphamide, to the standard therapy. It reduced the incidence of life-threatening acute GVHD from 10% to less than 5% and reduced debilitating chronic GVHD symptoms from 50% to less than 30%.”
However, the cyclophosphamide dose in that trial caused side effects in some people, including injury to the heart, lungs and kidneys. Patients also experienced more severe infections that required hospitalization.
“Our new trial is investigating two things,” Dr. Abedin said. “First, if giving half the dose of cyclophosphamide results in less injury to organs and less impact against the immune system in fighting infection. And second, if incorporating another medication approved for treating GVHD, ruxolitinib, will act as a preventive and further reduce risk.”
The drugs may complement each other in enabling the transplanted immune system to build tolerance to the host body. Cyclophosphamide affects the body’s regulatory T cells, a type of white blood cell, strengthening them to keep the immune system from overreacting and attacking the patient’s cells and organs. Ruxolitinib, a well-tolerated medicine without toxicities, may enhance the effects of cyclophosphamide and also suppress the immune system so it can become stronger without attacking recipient cells.
“There is always risk in trying to grow someone else’s immune system in your body,” Dr. Abedin said. “With this trial, we hope to maintain the latest improvements and deliver treatment in a way that achieves the same or better improvements in GVHD risk and severity — with substantially less toxicity. Our first goal is to cure leukemia and other blood cancers, but we also want people to have a good life.”
The trial was created by doctors within the Froedtert & MCW Blood and Marrow Transplant and Cellular therapy Program, a national leader in transplant-related care and research, advancing therapies and other targeted ways to save more lives. The program performs nearly 300 stem cell transplants a year.
“By making transplant safer, our hope is that more older people gain access to this potentially curative therapy,” Dr. Abedin said.
