Duke University, through the Immune Tolerance Network, is offering a multicenter, Phase III interventional clinical trial examining the efficacy of autologous hematopoietic stem cell transplantation, an emerging therapy for patients with active, treatment-resistant, relapse-remitting multiple sclerosis (MS). The condition causes inflammatory flares in the brain and spinal cord once every 12 to 15 months.
According to data generated from clinical trials in the U.S., Canada and Australia, risks with stem cell transplantation come with inherent risks. For example, such studies include a 1% mortality rate for those who opt for the approach to deal with MS. Interestingly, of the patients whose immune system reconstituted, data indicate that they were no longer experiencing new symptoms several years later, but the mortality risks are not fully known. What is known is that those patients who have undergone immune reconstitution therapy are especially susceptible to additional health risks such as secondary infection and even new neurological symptoms. For example, those patients that participated in an Alemtuzumab study found they experienced a high risk (33%) of secondary autoimmunity—often a thyroid or renal disease.
The multicenter, prospective rater-masked (blinded) randomized controlled trial of 156 participants comparing the treatment strategy of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) to the treatment strategy of Best Available Therapy (BAT) for treatment-resistant relapsing MS. All participants will be followed 72 months after randomization. The Phase III study started December 2019 and runs through October 2028. Duke is one of 21 research centers—the study, sponsored by the National Institute of Allergy and Infectious Diseases with collaboration from the Immune Tolerance Network and the Blood and Marrow Transplant Clinical Trials Network. TrialSite News earlier introduced the launch.
This study specifically compares stem cell transplantation of bone marrow against one of the four best available immune reconstitution therapies—natalizumab, alemtuzumab, ocrelizumab or rituximab—over a six-year period. Inclusion criteria includes participants with relapse-remitting MS, focusing on those who have had at least two inflammatory flares in the past two years or who have already had failed attempts at disease-modifying therapy.
Comparing ‘Apples to Apples’
As reported on by Lindsay Kenton, Clinical Practice Today, Suma Shah, MD, leads the study for Duke, one of the sites contributing to the study. Dr. Shah reports that this study was designed with the best-possible patients outcomes in mind noting “A lot of MS trials today compare something new that is very efficacious against either nothing or something that has been around since the early 1990s that is known to be a little weaker and needed lifelong.” She emphasized “it’s much harder to compare apples to apples in that case.”
Pragmatic Considerations: Cost
Moreover, the sponsors of the BEAT-MS trial considered stem cell transplantation therapy cost in terms of patients’ quality of life and cost of care. One key question that arises from this study: What is the cost differential between administering a one-time induction therapy versus an infusion every month to six months.
MS not Predictable and is Personalized
As Shah notes, “The trouble with MS is that it is very individualized and unpredictable, and when your resetting the immune system, you don’t really know what it’s going to reconstitute with”. But she emphasizes when the disease is “severely disabling” and unresponsive to current treatments, then “transplantation may be a promising alternative in spite of the risks.” What is there is a potential for a cure? Then for a patient who lives in an absolutely debilitating condition it just may be enough to “put more on the line for the chance of a cure.”
Shah notes that the Duke team brings specialists to bear on a study like this—resources “dedicated to safely mitigating” the various risks and “providing the fully comprehensive care that our patients deserve under one roof” quotes Shah.
The Blood and Marrow Transplant Clinical Trials Network (BMT CTN)
The Blood and Marrow Clinical Trials Network (BMT CTN), funded via the National Institutes of Health (NIH), was established because of a critical need for multi-institutional clinical trials focused directly on improving survival for patients undergoing hematopoietic cell transplantation (HCT). Launched in 2001, the BMT CTN has launched more than 30 multi-institutional Phase II and III trials involving more than 100 transplant centers, and in the process have enrolled thousands of patients.
The network represents a collaborative effort involving CIBMTR, the National Marrow Donor Program (NMDP)/Be the Match, and the Emmes Company, along with 20 Core Transplant Centers. Together all of these groups collaborate, cooperate, and serve as the BMT CTN Data and Coordinating Center to provide administrative, statistical, scientific and informatics support to all BMT CTN activities. See the link for organizational structure.
Lead Research/Investigators Duke
Suma Shah, MD, Duke primary investigator for Duke