First-of-its-kind clinical trial aims to improve outcomes in pediatric transplant patients

For the last 20 years, pediatric kidney transplant patients have been treated with the same immunosuppressive medication combinations and have been monitored using the same tests, without many new treatment options.

Unfortunately, unlike their adult counterparts, pediatric transplant recipients have not been included in clinical trials to test newer and promising combinations of medications that may help the immune system adapt to the transplanted kidney.

A clinical trial, spearheaded by David Briscoe, MB, ChB, director of Boston Children’s Transplant Research Program, and Nancy Rodig, MD, medical director of the Kidney Transplant Program — along with their colleagues at Duke Children’s Hospital — aims to change this.

“We want to move pediatric kidney transplantation into a new age of advanced treatment, monitoring, and care,” says Briscoe. “New and potentially improved anti-rejection medications have been developed in recent years, but they have not yet been tested in children in a clinical trial.”

Testing a new standard of care with medication combinations

To learn more, Briscoe, Rodig, and their colleagues are collaborating with major transplant centers across the U.S. and Canada to enroll 200 pediatric kidney transplant patients in the ADVANtage (Advancing Transplant Outcomes in Children) trial. This trial tests whether a regimen of a new class of immunosuppressive medications can inhibit disease-causing antibodies (which can lead to rejection) and change patients’ immune response to result in longer-term kidney transplant survival.

“The goal of this study is to determine if a new combination of medications in children is more effective at preventing the development of disease-causing antibodies and create an immunological state that can sustain the function of the transplanted kidney longer,” explains Rodig.

Patients who are enrolled in the trial will receive either a combination of belatacept (NULOJIX) and sirolimus or a more standard regimen of tacrolimus (Prograf) and mycophenolate mofetil (Cellcept). Belatacept belongs to a new class of medications that is FDA-approved for use in adults. The drug has also been successfully used in combination with sirolimus in adults and in a small number of pediatric transplant patients. In the ADVANtage trial, patients will receive a 30-minute intravenous infusion of belatacept once a month and daily doses of sirolimus by mouth.

As part of the trial, the team will use sophisticated testing to determine how the new medications are working, whether they are targeting molecules that cause rejection, and whether they are changing the patients’ immune response to promote long-term transplant survival.

“We don’t know yet which combinations of medications are truly the best to prevent rejection in pediatric patients, as they all target the immune system differently,” explains Rodig. “But we are optimistic that the new combination has advantages based on pilot studies in pediatric patients and many studies that have been performed in adult renal transplant patients. The once-a-month infusion will also be a benefit, as patients do not to need to take so many medications by mouth every day.”

Finding the right combination for the future

The current medication combination of tacrolimus and mycophenolate mofetil helps prevent the immune system from attacking the new kidney, but it does not prevent disease-causing antibodies in many children with kidney transplants. Also, tacrolimus does not allow the immune system to adapt well to the new kidney and can be somewhat toxic to the kidney, which is not optimal for long-term kidney function.

All immunosuppressive medications have side effects, and patients receiving the new combination will be extensively monitored for any complications by their care team. But if significant benefits are seen through the new medication combination, the trial could result in a better option of care for many pediatric kidney transplant patients.

“Learning which combination of medications works best in our kidney transplant patients would greatly improve the general health and well-being of children with kidney failure,” notes Rodig.

Who is eligible for the ADVANtage Trial?

Patients between the ages of 6 and 21 years who are receiving their first kidney transplant can be considered to participate in the clinical trial. Patients need to have lab studies that confirm the previous history of and recovery from a certain viral infection (Epstein-Barr virus) to be able to participate. The trial will start with patients over 13 years old. All patients will be monitored for the first two years post-transplant as they take their anti-rejection medication combination. Enrollment in the ADVANtage trial has just opened.

This clinical trial has received funding from the National Institutes of Health and support from the National Institute of Allergy and Infectious Diseases.

To learn more, contact Dr. Nancy Rodig at nancy.rodig@childrens.harvard.edu , Dr. David Briscoe at david.briscoe@childrens.harvard.edu , or clinical research specialist Emily Toal at emily.toal@childrens.harvard.edu