Clinical Studies Search

Protocol Summary

Protocol No.
Prinicipal Investigator
McGregor, Lisa
Phase III
Age Group
Secondary Protocol No.
A Phase 3 Randomized Trial for Patients with de novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 with GO, and the Addition of the FLT3Inhibitor Gilteritinib for Patients with FLT3 Mutations
Exploratory Objectives
Evaluation of MRD Pre-HSCT
The use of pre-transplant measurable residual disease (MRD) testing is emerging as the most important indicator of prognosis with HSCT for AML. A retrospective analysis performed by the Fred Hutchinson Cancer Research Center of 253 children and adults (median age=43 years) transplanted for AML in morphologic CR1 or CR2, demonstrated a cumulative incidence of relapse exceeding 60% in patients who had pre-transplant MRD assessed by MDF. A multivariate analysis demonstrated a relative risk for relapse of 4.9 (p < 0.001) and that the importance of other traditionally important prognostic factors, including cytogenetic risk and remission number, was obviated by MRD status.127

The results of two smaller pediatric only studies of pre-transplant MRD assessed by MDF are consonant with these results. In a study of 123 children in morphologic CR1 or CR2 performed by the Pediatric Blood and Marrow Transplant Consortium, the cumulative incidence of relapse in those with MRD (n=10) was 70%.128 In an analysis by COG of 108 children in a morphologic CR1 using experience from AAML 03P1 and 0531, the cumulative incidence in those with MRD (n=20) was 65%.129

More definitive research on pre-transplant MRD in children with AML is needed. The larger sample size afforded by AAML1831 will not only allow us to confirm the results of the earlier two studies, but would also permit informative secondary analyses. As such, we would be able to assess whether there is an association between level of MRD and risk for relapse. We would also be able to assess potential interactions between MRD and other risk factors.

Metabolomic Profiling in Allogeneic HSCT Patients
Substantial insight regarding drug metabolism and response has been gained through the use of metabolomics the profiling of a broad range of small molecules present in biological fluids.130-136 For example, recent metabolomics studies have provided insight regarding potential biomarkers for graft versus host disease (GVHD) in allogeneic HSCT recipients.137, 138 More specifically, Clayton, et al., introduced the concept of personalized drug treatment using pre-dose metabolite profiling to predict drug response in individual subjects, which the authors termed, pharmacometabonomics .134, 135 In allogeneic HSCT, pre-dose metabolite profiling has been associated with busulfan pharmacokinetics139, 140 and acute GVHD.138 Day +7 serum metabolite profiling has also been associated with acute GVHD and relapse.141

Applicable Disease Sites
Other Hematopoietic
Participating Institutions
Hershey Medical Center