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Novel 3D Hematological Malignancy Organoid to Study Disease Biology and Chemosensitivity (Organoid)

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ClinicalTrials.gov Identifier: NCT03890614
Recruitment Status : Recruiting
First Posted : March 26, 2019
Last Update Posted : November 3, 2022
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

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.

Condition or disease Intervention/treatment
Hematologic Malignancy Other: Ancillary-Correlative - Creation of three-dimensional myeloma organoids using marrow aspirates

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.

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Study Type : Observational
Estimated Enrollment : 70 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Novel 3D Hematological Malignancy Organoid Platform to Study Disease Biology and Perform Chemosensitivity Assays for Patient-Specific Care
Actual Study Start Date : May 16, 2019
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Intervention Details:
  • Other: Ancillary-Correlative - Creation of three-dimensional myeloma organoids using marrow aspirates
    Bone marrow aspirates will be collected from participants with hematologic malignancy being evaluated for relapsed disease to create three-dimensional constructs using a three-dimensional bioprinting methodology for automated organoid biofabrication.

Primary Outcome Measures :
  1. Proportion of Live/Dead Myeloma Cells Using Bioprinting Technology [ Time Frame: Up to 5 days ]
    Bone marrow aspirates (around 3-7 ml) will be collected from patients with hematologic malignancy being evaluated for relapsed disease. The samples will be used to create 3D organoid constructs using a 3D bioprinting technology for automated organoid biofabrication using hyaluronic acid and gelatin-based hydrogel. The 3D organoid constructs allow extended time to simulate the protective environment cancer cells use to survive in bone marrow. Organoids will be assessed at 1, 3, and 5 days for viability of myeloma cells. Based on live/dead cells using fluorescent imaging, the hydrogel composition will be modified to allow the optimal media for cell survival ex vivo.

  2. Tumor-Stroma Interactions [ Time Frame: Up to 5 days ]
    To assess the interaction of myeloma cells with stromal cells in a 3D organoid model, plasma and myeloma cells will be labeled using differing colors of Vybrant Multicolor Cell Labeling Kit to allow visualization of the cells' nuceli. By confocal microscope, slides will be evaluated for Vybrant-labeled hematologic malignant cells or healthy plasma cells (different colors) to identify preferential cell interactions. These aspects of tumor interaction with its stromal microenvironment will provide critical knowledge to better understand its biology.

Secondary Outcome Measures :
  1. Number of Reduced Hematologic Malignant Myeloma Cells [ Time Frame: Up to 3 days ]
    After 24 hours of incubation, chemotherapy agents will be added at prepared concentrations that fall within the prescribed therapeutic ranges. A maximum of 15 combinations for each donor will be allowed for testing after which the efficacy of the treatments will be assessed qualitatively (live/dead straining) and quantitatively and quantitatively (automated segmentation and quantification of live/dead staining, mitochondrial metabolism/ATP activity, and ratio of Annexin V staining versus Ki67 staining [apoptosis versus proliferation]). These metrics will capture the reduction in hematologic malignant cell population.

  2. Comparison of Cell Viability [ Time Frame: 24 and 36 hours ]
    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.

  3. Organoid Responses Compared to Clinical Response [ Time Frame: Up to 3 months ]
    The response to each chemotherapy agent from obtained three-dimensional organoids will be compared to actual clinical responses of each participant through retrospective chart review to obtain regimen used to treat disease and the level of measurable disease in serum at different time points of treatment. The time points would include time of marrow biopsy, after 2 cycles of treatment and after 4 cycles of treatment.

Biospecimen Retention:   Samples Without DNA
Bone marrow

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Hematologic malignancy patients undergoing transplant.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03890614

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Contact: Study Nurse 336-716-2957 cagonzal@wakehealth.edu
Contact: Study Coordinator 336-713-5878 dfunes@wakehealth.edu

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United States, North Carolina
Wake Forest Baptist Comprehensive Cancer Center Recruiting
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
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Principal Investigator: Timothy Pardee, MD, PhD Wake Forest University Health Sciences
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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03890614    
Other Study ID Numbers: IRB00057612
Crowdcare Foundation ( Other Grant/Funding Number: GTS 47809 )
Pilot Fund ( Other Identifier: CTSI )
P30CA012197 ( U.S. NIH Grant/Contract )
WFBCCC26A19 ( Other Identifier: WFCCC )
First Posted: March 26, 2019    Key Record Dates
Last Update Posted: November 3, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Wake Forest University Health Sciences:
3D organoid technique
Additional relevant MeSH terms:
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Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases