The objective of this project is to compare chemo­sensi­tiv­ity be­tween chemo­ther­apy com­bi­na­tions in bone marrow aspirates using 3D organoid models. The investigators overarching hypothesis is that 3D organoids are ideal to test chemo­sensi­tiv­ity in real time, to provide personalized medicine and guidance in the setting of re­lapsed multiple myeloma and poten­tially other cancers.

Enrollment status: Not yet recruiting.
Estimated start date: April 2019.

Countries with trial sites (# of sites): Unknown at this time.

Type of trial: Observational.
Phase of trial: Not specified.

Trial IDs: NCT03890614, WFBCCC 26A19.

Detailed Description

Optimize the novel 3D organoid technique already used to recreate myeloma tumors in the Regenerative Medicine laboratory.

Optimize cell viability of myeloma organoids to extend avail­able time in cul­ture by screen­ing cell cul­ture media cytokines and 3D extracellular matrix composition (current en­viron­ment is able to main­tain cells alive for up to 5-7 days to allow testing).

Evaluate myeloma tumor markers at dif­fer­en­t time points of organoid life to con­firm accurate tumor rep­re­sen­ta­tion, identify genetic ex­pres­sion char­ac­ter­istics, unique mutations, and tumor-stroma inter­action. This will give in­for­ma­tion of the tumor char­ac­ter­istics to learn about tumor biology and correlate with responses.

Evaluate chemo­sensi­tiv­ity on patient derived 3D organoids. Using myeloma patients marrow aspirate, eval­u­ate live/kill rates of myeloma cells after being exposed to estab­lish­ed regi­men com­bi­na­tions after 24 and 36 hours of exposure at pre-determined con­cen­tra­tions.

Using patient samples, eval­u­ate dif­fer­ences in gene ex­pres­sion and cell markers of the myeloma cells that remained alive after chemo­ther­apy exposure to better under­stand mech­a­nisms of resistance.

Validate the predictive value of the 3D organoid chemobiogram results compared with retro­spec­tive­ data of the donor s responses to the treat­ment used at that time point. This will compare in vivo/ex vivo responses and facilitate future personalized medicine. Chemobiogram is the report on chemo­sensi­tiv­ity from the com­bi­na­tions tested much like an antibiogram

Additional trial in­for­ma­tion at clin­i­caltrials.gov: link.