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Increased sensitivity of minimal residual disease monitoring using peripheral blood in pediatric patients with acute lymphoblastic leukemia

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R44CA224848-01A1
Agency Tracking Number: R44CA224848
Amount: $348,768.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 102
Solicitation Number: PA17-302
Timeline
Solicitation Year: 2017
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-07-18
Award End Date (Contract End Date): 2021-06-30
Small Business Information
321 S COLUMBIA ST, CB 7063
Chapel Hill, NC 27599-0001
United States
DUNS: 808078765
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 ROLF MULLER
 (858) 336-2777
 rmuller@biofluidica.com
Business Contact
 JDUY MULLER-COHN
Phone: (858) 336-2777
Email: judymullercohn@biofluidica.com
Research Institution
N/A
Abstract

Abstract
Acute lymphoblastic leukemiaALLis the most common malignant disease in childhood and accounts for
approximatelyof all cancers diagnosed before the age ofyearsThe primary cause of death for ALL
patients is disease relapseThereforemonitoring for minimal residual diseaseMRDis considered the most
powerful predictor of outcome in acute leukemiasincluding B type acute lymphoblastic leukemiaB ALLIf
clinicians could identify a patient s MRD before the tumor cells rapidly expand to florid relapsepreemptive
therapies could be undertaken with better patient outcomeFor pediatric B ALLthere are existing tests for
monitoring relapse from MRD including PCR or multi parameter flow cytometrybut require a bone marrow
aspiratewhich can be painful and limits the frequency of testingIf MRD could be detected in B ALL
patients from peripheral blood and not bone marrowthe corresponding assay could assist in guiding therapy to
enable precision medicine resulting in better patient outcomeIn this applicationan innovative test that consists of a microfluidic assay and the associated hardware will be
developedThe test can provide high clinical sensitivity for MRD testing and permits frequent minimally invasive
sampling using peripheral bloodmLas opposed to an invasiveespecially for pediatric patientsbone marrow
biopsyThe assay uses a microfluidic device to analyze peripheral blood and search for circulating leukemic
cellsCLCsUsing this microfluidic assay in a longitudinal study of acute myeloid leukemiaAMLpatients
following stem cell transplantationMRD via monitoring of CLCs was detectedmonths earlier compared to
both multi parameter flow cytometryMFCand PCRwhich used bone marrow aspiratesthe microfluidic assay
wasorders of magnitude more sensitive than PCR and MFCOwing to the ability of the microfluidic assay to
detect CLCs in bloodmore frequent testing of a patientsdisease status was possible when compared to bone
marrow biopsy testingFor B ALLanti CDantibodies immobilized within a microfluidic device can affinityselect cells expressing CDsurface antigen commonly expressed by B ALL lymphoblastsi eCLCand
normal B cellsCLCs are identified by expression of aberrant markerssuch as Terminal deoxynucleotidyl
TransferaseTdTand the number of CLCs tracked to determine the onset of relapse or the risk of relapseIn this SBIR Phase I II fast track proposalthe CLC microfluidic test will be expanded and developed for
commercialization to monitor MRD and potential relapse in B ALL pediatric patients to provide coverage ofGiven the strong data generated to date and the urgent diagnostic need for an improved easy to implement
MRD assay for frequent monitoringthe proposed test fills an unmet clinical need in the area of pediatric
oncologyAs a notethe test can be reprogrammed to search for other pediatric oncological diseases such as
T cell ALLrequires only a change in the cell selection antibodyNarrative
Acute lymphoblastic leukemiaALLis the most common malignant disease in childhood and accounts forof all cancers diagnosed before the age ofyearsThe primary cause of death for ALL occurs due to disease
relapseMonitoring of minimal residual diseaseMRDis considered the most powerful predictor of outcome in
acute leukemiasincluding B type acute lymphoblastic leukemiaB ALLIf clinicians could pinpoint when a
patient s minimum residual diseaseMRDbegins rapid expansion to relapsepreemptive therapies can be taken
to dramatically improve patient outcomeIn this Phase I II applicationa fully automated instrument that can
process peripheral blood directlysearch for circulating leukemic cellsCLCsin pediatric ALL patientsand
detect relapse earlier than current techniques will be developedThis application represents a significant
improvement to standard of care that requires painful bone marrow aspirates in children to monitor MRD

* Information listed above is at the time of submission. *

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