Guidance for Developing Phase II Cell Therapy Trial Proposals for Consideration by the Blood and Marrow Transplant Clinical Trials Network

Many innovative cell therapies that directly relate to hematopoietic stem cell transplantation are at an early stage of development and until recently, most were not ready to progress to later phase multicenter studies. However as the field has matured, it is likely that some strategies will be ready to test in later phase studies and pathways will need to be established for undertaking such trials. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) anticipates being able to provide infrastructural support for a limited number of such studies when the goal of the novel cell therapy is to improve the outcome of transplant by reconstituting antitumor or anti-infectious immunity or modulating alloreactivity or to use transplant as a means of genetic correction for inherited diseases. This brief report is intended to assist investigators by outlining the process by which such studies can be submitted, and reviewed and implemented by the BMT CTN. The BMT CTN was established in 2001 by the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) as an infrastructure to conduct multi-institutional Phase II and Phase III trials focused on improving outcomes in blood and marrow transplantation (BMT). The BMT CTN is a network of 16 Core Transplant Centers/Consortia, more than 60 Affiliated Transplant Centers, and a Data Coordinating Center (DCC). Its activities are overseen by a Steering Committee composed of representatives from the Core and Affiliate Centers, the DCC, NHLBI and NCI (www.bmtctn.net). Many prominent advances in clinical oncology have resulted from cooperative group trials, underscoring the importance of collaborative clinical trials to the medical community. The BMT CTN is conducting more than 20 Phase II and Phase III trials to address issues critical to BMT patients. Although the results of most of these trials are still forthcoming, these studies have the potential to change practice and establish a new standard of care. Eleven BMT CTN trials have completed enrollment; patient follow-up continues on five of these, with data analysis in progress or recently completed for the others. Accrual continues on 11 trials with four additional trials expected to open in 2010. Although the BMT CTN considers issues relevant to both autologous and allogeneic BMT, it has a major focus on allogeneic transplantation. Of the 400–600 patients enrolled on BMT CTN trials annually, more than 80% are allogeneic transplant recipients. The BMT CTN infrastructure may be used to conduct multi-institutional Phase II studies that would either establish the efficacy of novel cell therapies to a level that would justify a large Phase III trial. For rare diseases or indications, licensure may be possible with a smaller study - for example European investigators have received orphan drug designation from the European Medicines Agency for gene transfer to hemopoietic stem cells to treat ADA deficiency based on studies with small numbers of patients. Study requirements for specific indications should be discussed with the FDA. A number of steps need to be followed for a cell therapy phase II/III trial to be supported by the BMT-CTN.