The U.S. Postal Service's motto, "Neither snow nor rain …" aptly describes the tenacity of a far-reaching Clinical Research Division study involving post-transplant patients from throughout the United States, as well as frequent blood draws and immediate treatment if needed. Using tools like e-mail and overnight couriers, the success of the unique trial has hushed naysayers who said such a complex effort couldn't be done.
The multi-center, double-blind study, underway since 2001, has recruited 156 bone-marrow and/or stem-cell transplant patients who hail from more than 100 cities in 36 states. Led by Dr. Michael Boeckh, principal investigator of the Program in Infectious Disease, the patients begin study participation once they are back at home following their transplants. Each is given an antiviral drug, valganciclovir, or placebo in an effort to determine if the medication can prevent occurrence of a life-threatening infection, cytomegalovirus (CMV).
CMV can lie dormant in a person's body, much like the herpes virus does in people who get cold sores. Weakened immunity following transplantation leaves a patient vulnerable to CMV, which can strike even months after the procedure. It's a feared diagnosis; CMV pneumonia is fatal half of the time. Currently, valganciclovir is the standard CMV treatment after diagnosis, but researchers want to know if prophylactic doses will prevent CMV altogether. Recruitment ends in about a year, and the study results should be known in about three years.
For approximately six months the study participants provide weekly blood samples, which are sent to the study's coordinating center at the Hutchinson Center via overnight courier. The blood is tested for CMV and the patient's white blood-cell count is monitored for any decreases, a known side effect of treatment.
As part of their normal post-transplant care, patients need regular blood draws, so the frequent treks to the doctor's office or lab would be routine anyway, but it's not necessarily easy for participants in remote areas.
"One person in the study had to drive an hour just to get to the doctor's office. The patient lived in a town so remote that Fed Ex wouldn't even deliver to her home," said Christi Dahlgren, the primary research nurse for the CMV study.
Fortunately, the unpredictability of Mother Nature hasn't presented too many obstacles for the study. "Sometimes weather becomes an issue in the winter time," Dahlgren said. "For the most part, we've been lucky regarding problems with weather or the overnight carrier." The Center has received almost 4,000 blood specimens over the course of the study, and 85 percent are received within 24 hours of the blood draw.
'One less thing to worry about'
For their efforts, participants are rewarded with careful, consistent monitoring and quick follow-up. CMV test results, which take four days to obtain in a typical setting, are ready within 24 hours. If the tests show CMV, more than 80 percent of the patients begin treatment within 48 hours of the initial blood draw. "Within minutes of getting a positive result, I call the patient and instruct them to stop taking the study drugs and start taking the medications, which we give them at the beginning of the study, just in case a CMV infection develops. They don't need to see their doctor or pick up a prescription. All of these actions are communicated with the patient's local physician," Dahlgren said.
In addition to testing for CMV, Center staff members manage any adverse effects from the study drugs, and adjust the dosage based on kidney-function tests.
"It was good knowing that the CMV test was getting done. It was one less thing for me to worry about," said a former Seattle Cancer Care Alliance (SCCA) patient who traveled from Fairbanks, Alaska, for treatment of chronic myeloid leukemia in 2004 and participated in the CMV study. "In Fairbanks, the care was not as regimented, so I was glad to know my blood was being tested weekly."
"The study was definitely my lifeline back to Seattle. I called Christi my 'go-to girl.' Several times, I had questions not related to CMV, and she routed me to the proper person. She always kept me informed about my test results. Everything I asked her to do, she helped me get answers."
Another CMV study participant agrees with Sharp's assessment. "I jumped at any study I could be involved in because the Hutchinson Center worked a miracle for me," said the western Colorado resident, who was treated at the SCCA for acute myeloid leukemia in 2004. "I felt like I was getting very personal attention. I felt real good about my constant contact with the Hutchinson Center because they were professionals, and I knew I had plenty of people I could ask questions of and they'd know the answers and take the time with me."
Despite the frequent blood draws, study paperwork and phone calls, Dahlgren said often patients aren't in any hurry to end their participation. "When they complete the treatment phase of the study, many are hesitant to come off because they really like the intense monitoring, communication and attention," she said. After the treatment period, participants are called quarterly for another year to monitor their health.
The formidable study logistics require careful organization. "There's a lot involved to make this study work," said Dahlgren, who credits assistant Elisa Minerich for her critical efforts in preparing, mailing and tracking the study kits. "The study can be exhausting on the logistical end. We created a database to help manage all of the tasks required by the protocol. I have to be prepared to act quickly when there are changes in the subject's labs and to constantly prioritize my duties."
Proof is in high compliance
As a testimony to Dahlgren's efficiency and effectiveness, in her two years as study coordinator, not a single participant has dropped out of the study. "We have a high compliance rate because they like to feel safe knowing their lab work is being monitored so closely and to also know they are still connected to the Center, whether they live in a remote town or across the country," she said.
The now-proven feasibility of such a trial has attracted the attention of other cancer researchers. Dahlgren will present this study to oncology nurses next month at the American Society for Blood and Marrow Transplantation meeting in Honolulu, Hawaii.
The success of this long-distance study model has also spawned similar studies at the Center. Boeckh and pulmonologist Dr. Jason Chien just began a study of common viruses and long-term breathing difficulties in post-transplant patients after they have returned home.
"The CMV study is a great success story," Boeckh said. "It's fantastic that we can manage a patient on a research study regardless of location — anywhere in North America, basically. Many say you can't do studies like this, but our group has great experience in making these things happen."