SUPPLEMENTARY INFORMATION:

I. Background

Complete remission, relapse-free survival, and overall survival are frequently used as endpoints in clinical trials of new therapeutics for AML. These endpoints have some limitations, especially in the context of minimal residual disease. Use of morphological complete remission may miss individuals with clinically significant residual disease who are not truly in remission. For those being followed after remission induction, new evidence of submorphological disease may prompt therapy before morphological relapse. Additionally, for patients with good prognosis, the length of the clinical trial followup may be very long when survival is the outcome measured, raising logistical and financial challenges for study conduct. More information is needed on whether MRD in AML can be qualified as a response biomarker and then used as a clinical trial endpoint and what the challenges would be to implement use of such an endpoint.

This Public Workshop on Minimal Residual Disease in AML will be one of a series of FDA workshops to establish processes and procedures necessary to qualify a prognostic biomarker, MRD, as a possible response or efficacy biomarker in a group of hematological malignancies. Evaluation of clinical data suggests that MRD can be established as a potential surrogate endpoint for pivotal clinical trials and drug approval given its prominent role as a prognostic indicator in certain subtypes of acute and chronic leukemia. The Office of Hematology and Oncology Products has explored, or plans to explore, the potential utility of MRD as a surrogate endpoint in acute lymphoblastic leukemia (ALL) (including the relapsed setting), chronic lymphocytic leukemia (CLL), and AML. Given the diverse pathophysiology and natural history of these diseases and current practice standards, individualized consideration of MRD as a surrogate endpoint is warranted. The ALL workshop was held on April 18, 2012, and the CLL workshop will be held on February 27, 2013.

II. Structure and Scope of the Workshop

The workshop's scope will include discussions of the use of flow cytometry and molecular methods used to detect and measure minimal residual disease in patients being treated for AML. The workshop will consist of formal presentations examining the regulatory, scientific, and clinical basis for use of biomarkers as potential clinical trial endpoints in AML interspersed with discussions on issues associated with these endpoints.

III. Attendance and Registration

FDA encourages patient advocates, representatives from industry, consumer groups, health care professionals, researchers, and other interested persons to attend this public workshop. There is no registration fee for the public workshop. To register electronically, please use the following Web site: http://www.zoomerang.com/​Survey/​WEB22GPAXN9NQB (FDA has verified the Web site address, but we are not responsible for any subsequent changes to the Web site after this document publishes in the Federal Register .) Seats are limited and conference space will be filled in the order in which registrations are received. Onsite registration will be available to the extent that space is available on the day of the conference.

Information regarding special accommodations due to a disability, visitor parking, and transportation may be accessed at: http://www.fda.gov/​AdvisoryCommittees/​default.htm. Under the heading “Resources for You,” click on “Public Meetings at the FDA White Oak Campus.”