The University of Alabama at Birmingham (UAB) is recruiting patients with newly diagnosed multiple myeloma for a Phase 2 trial evaluating an innovative treatment approach with the goal of completely eradicating the disease.
Led by UAB researchers, the clinical trial, called MASTER (NCT03224507), will assess the safety and effectiveness of a combination of anti-myeloma medications, immunotherapy, and stem cell transplant from a patient’s own blood stem cells — a procedure called autologous hematopoietic cell transplantation.
One of the biggest innovations of the approach is the use of next-generation DNA sequencing to detect minimal residual disease down to a level of one cancer cell in 100,000. That is a large jump in terms of sensitivity to detect myeloma cells, enabling a 100- to 1,000-fold more sensitive detection than traditional methods.
The objective of the approach is to reach complete eradication of multiple myeloma.
Normally, therapies to treat this cancer are tested using less sensitive methods to measure disease response. As a result, patients in remission may still have many cancer cells that are not detected with current methods, and are indistinguishable from those who have achieved true eradication.
The MASTER trial’s goal is to treat patients until sequencing confirms total elimination of the multiple myeloma. DNA sequencing will allow much more reliable monitoring and the detection of relapses earlier than ever and even before symptoms start.
Researchers plan to enroll 82 patients with newly diagnosed multiple myeloma. In addition to UAB, Vanderbilt University Medical Center, Duke University, Medical College of Wisconsin, University of Wisconsin, and Oregon Health and Science University are also recruiting for the trial.
Patients will first be treated with four 28-day cycles of a combination of agents proven to be effective in eliminating minimal residual disease, including dexamethasone, Revlimid (lenalidomide), Darzalex (daratumumab), and Kyprolis (carfilzomib).
After this first phase of therapy, patients will be evaluated to receive an autologous stem cell transplant. If, after the transplant, the patient still has detectable multiple myeloma, he or she will be treated with rounds of consolidation therapy, essentially consisting of cycles of the same combo therapy applied in the beginning.
After each phase, patients will be checked for minimal residual disease by sequencing. Those whose cancer cells are completely eliminated will continue to be monitored for relapse.
Those patients who still have detectable cancer cells will receive maintenance treatment with Revlimid. Maintenance will proceed until disease progression or intolerance.
“I believe for the first time that we have treatments that are effective enough to make it possible to eradicate multiple myeloma definitively in a substantial proportion of patients, along with having the technology to detect that the disease has been targeted and that treatment can be stopped,” Luciano Costa, MD, PhD, a scientist at the UAB Comprehensive Cancer Center, and principal investigator of the MASTER study, said in a UAB news release.
“That is what patients want, after all — a treatment that gives them the possibility of eliminating any trace of the myeloma without having to be on therapy for the rest of their lives. It is a bold move, but bold moves are what our patients deserve,” he said.