Prospective Clinical Trials in BMT Come of Age in the US: The Blood and Marrow Transplant Clinical Trials Network

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About 8 years ago, a small group of individuals raised the notion of establishing a clinical trials network that would be dedicated to addressing, prospectively, the key clinical issues in blood and marrow transplantation. The enterprise would be funded jointly by the National Heart, Lung and Blood Institute (NHLBI) and the National Cancer Institute (NCI) with important input from two existing clinical bone and marrow transplant (BMT) networks, the National Marrow Donor Program (NMDP) and the International Blood and Marrow Transplant Registry (IBMTR)/Autologous Blood and Marrow Transplant Registry (ABMTR) (now affiliated as the Center for International Blood and Marrow Transplant Research (CIBMTR). Although a controversial idea then, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) was nevertheless born in 2001 in much the way that it had been proposed. At the time, some in our community argued that it was unnecessary because cancer cooperative groups had addressed successfully some of the important issues in BMT and would continue to do so, that federal funds would be diverted from individual centers with a track record of tackling clinical BMT issues in an innovative way, and that many, especially smaller BMT centers, would be excluded from participation. Other no less compelling arguments were also raised.

It is particularly heartening, therefore, that the article by Weisdorf et al of this issue of BBMT dispels virtually all of those concerns and provides an update on how this venture has progressed. Indeed, the BMT CTN can claim remarkable success: total accrual to prospective clinical trials now exceeds 1400 patients since the Network was established. The studies span the gamut of issues in BMT and include comparisons of graft sources, approaches to reducing regimen-related toxicity, optimum management of graft-versus-host disease, and assessment of late effects and quality of life, to name only some that are underway.

It is noteworthy that at least one trial is in collaboration with a cooperative oncology group (in this case Cancer and Leukemia Group B (CALGB), an approach that strengthens both organizations and provides a complementary model to address transplant- and disease-related issues simultaneously. The BMT CTN is especially constituted to address transplant-specific issues and, as Weisdorf and colleagues point out, has embarked on a number of ambitious studies, including the comparison of bone marrow versus filgrastim mobilized peripheral blood cells for unrelated donor hematopoietic cell transplantation, an important randomized trial that would be difficult to conduct by any other group and certainly not as quickly. An expected strength of the Network would be the adequate accrual to trials involving rare diseases; hence, a study is underway to investigate reduced transplant-related toxicity in patients with aplastic anemia. Opportunities also appear to be available for the Network to evaluate phase II data from single centers as the basis for Network-sponsored prospective phase III trials. This may be a particularly appealing vehicle for large centers to have their innovative ideas evaluated prospectively.

Weisdorf et al also outline the organizational structure of the CTN. Sixteen core centers and 50 noncore centers participate in the Network. It is run by a Steering Committee that includes representatives from the core centers, the funding agencies, and others. Given the structure of the Network, it appears that most centers have adequate access and are able to participate in Network-sponsored trials.

The BMT CTN is still a young organization. Its challenges include how to optimize interactions with cooperative cancer groups, how to invite the participation of centers outside the designated 50 noncore centers that nonetheless can contribute patients and ideas, how to incorporate key translational studies in the CTN protocols, and ultimately, with the limited resources available, how to identify the studies that will move the field forward substantively. For example, it is beautifully placed to conduct molecular epidemiology studies (using patient and donor tissue), which may provide profound insights into how best to manage patients with BMT. This will require additional resources and expertise, but given the foresight of its founders, there is cause for considerable optimism that much will be accomplished by the BMT CTN.