Feasibility of predicting AML response to induction chemotherapy

Period of Performance: 09/01/2017 - 08/31/2018

$300K

Phase 1 SBIR

Recipient Firm

Accelerated Medical Diagnostics, LLC
DAVIS, CA 95618
Principal Investigator

Abstract

Abstract There is a critical unmet medical need for a rapid, accurate test to identify AML patients who are likely to respond to chemotherapy. Presently, induction chemotherapy with the DNA damaging drugs cytarabine (ARA- C) and idarubicin (IDR), known as 7+3, is the standard of care for most of these patients. However, 7+3 is a relatively ineffective therapy, particularly in older patients, and has serious therapy- related toxicities. Accelerated Medical Diagnostics is developing the InductDx test to identify those patients whose AML will respond to 7+3 induction chemotherapy. The test utilizes ex vivo diagnostic microdoses (~1% of the therapeutic dose) of 14C- labeled ARA- C and 14C- labeled IDR. Extremely low levels of 14C label are quantified in cancer cells isolated from patient blood samples using accelerator mass spectrometry (AMS). AMS is the most sensitive technology available for quantifying radiolabeled compounds in biological samples. We hypothesize that a threshold level of drug- DNA damage is required for 7+3 efficacy, and the level of microdose- induced drug- DNA damage is predictive of the capacity of AML cells to attain that threshold during in vivo chemotherapy. The extent of microdose- induced drug- DNA damage in cell cultures and AML patient samples will be compared with cellular sensitivities and retrospective patient response to 7+3 therapy as proof- of- concept for clinical development of the InductDx test for AML.