Clinical trial NCT03890614: Novel 3D Hematological Malignancy Organoid to Study Disease Biology and Chemosensitivity
Official title: Novel 3D Hematological Malignancy Organoid Platform to Study Disease Biology and Perform Chemosensitivity Assays for Patient-Specific Care
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hematologic Malignancy
Keywords: 3D organoid technique
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-03-26
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Hematologic malignancy patients undergoing transplant.

Brief summary: 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 hematologic malignancy and potentially other cancers.

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.

Eligibility criteria: Inclusion Criteria:

* Patients with suspected or confirmed hematologic malignancy undergoing a bone marrow biopsy as part of their care.
* The ability to understand and willingness to sign an IRB approved informed consent document.

Primary outcomes:
measure: Proportion of Live/Dead Myeloma Cells Using Bioprinting Technology
timeFrame: Up to 5 days
measure: Tumor-Stroma Interactions
timeFrame: Up to 5 days
Secondary outcomes:
measure: Number of Reduced Hematologic Malignant Myeloma Cells
timeFrame: Up to 3 days
measure: Comparison of Cell Viability
timeFrame: 24 and 36 hours
measure: Organoid Responses Compared to Clinical Response
timeFrame: Up to 3 months
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Timothy Pardee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: