A Pilot Study of Biomarkers for Personalized Early Assessment of Response During Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Effective treatment of patients with relapsed and refractory acute myeloid leukemia (RR-AML) remains a significant unmet need. Current response criteria were originally proposed in 1956 and do not provide a sensitive assessment of AML disease burden, as evidenced by the disconnect between the apparent success of current induction therapy in achieving complete remission in most patients and the stark reality of median overall survival times of less than two years. While sensitive minimal/measurable residual disease assays assessing AML disease burden have been developed, the role for these tests in the treatment algorithm for patients with RR-AML has yet to be defined. We propose evaluating if these high sensitivity assays could function as early predictors of salvage therapy failure.

This protocol is designed as a feasibility study to evaluate if use of high sensitivity peripheral blood-based molecular assays on day 4 of induction salvage chemotherapy can predict failure to ultimately achieve a CR or CRi in patients with RR-AML. Eligible patients will receive salvage induction therapy using FDA approved antineoplastic agents given either alone or in combinations as defined in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for AML.

Additional secondary objectives include investigating the relationship between kinetics of gene expression changes and response to chemotherapy, determining the proportion of patients for whom results of day 4 peripheral blood gene expression testing are available before day 8 of therapy, determining the proportion of patients for whom results from pre-treatment molecular and genetic testing are available before day 8 of therapy, assessing patient and disease specific factors associated with failure to achieve a CR, determining the feasibility of measuring AML residual disease burden using alternative technologies and alternative tissue sources, determining the proportion of patients who receive allogeneic hematopoietic stem cell transplant after completion of therapy, determining the incidence of infectious complications with the use of modern prophylactic antimicrobial agents compared with historical comparisons and determining the feasibility of recruiting patients with RR-AML to the NIH Clinical Center.