Ignite Creation Date:
2024-05-06 @ 4:15 PM
Last Modification Date:
2024-10-26 @ 2:06 PM
Study NCT ID:
NCT04920188
Status:
TERMINATED
Last Update Posted:
2024-07-05
First Post:
2021-06-03
Brief Title:
Development and Application of a Novel Digital Array PCR for Acute Myeloid Leukemia AML
Sponsor:
UNC Lineberger Comprehensive Cancer Center
Organization:
UNC Lineberger Comprehensive Cancer Center
Study Overview
Official Title:
LCCC 2103 Development and Application of a Novel Digital Array PCR Assay for Evaluation of Minimal Residual Disease in Acute Myeloid Leukemia AML
Status:
TERMINATED
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Resources related issues
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Purpose The purpose of this trial is to investigate whether a digital array assay can detect trace amounts of residual leukemia and predict relapse in acute myeloid leukemia AML patients in remission who have undergone allogeneic stem cell transplantation SCT at the North Carolina Cancer Hospital NCCH
Participants Adult patients 18 years of age or older with diagnosed AML who are going to undergo stem cell transplant SCT
Procedures methods A total of 10 eligible subjects will be treated per standard of care with SCT Peripheral blood and bone marrow aspirate 10 mL each for digital array assay analysis will be collected along with routine lab draws and bone marrow biopsy procedures prior to SCT Beginning 1 month after SCT peripheral blood 10 ml will be collected to assess MRD by digital array assay analysis on a monthly basis for up to 6 months In addition bone marrow aspirate will be collected at approximately Month 3 and 6 following SCT for assay analysis Patient medical records will be reviewed 6 and 12 months after completing their last MRD follow up assessment to confirm survival status remission status and gather information related to relapse
Participants Adult patients 18 years of age or older with diagnosed AML who are going to undergo stem cell transplant SCT
Procedures methods A total of 10 eligible subjects will be treated per standard of care with SCT Peripheral blood and bone marrow aspirate 10 mL each for digital array assay analysis will be collected along with routine lab draws and bone marrow biopsy procedures prior to SCT Beginning 1 month after SCT peripheral blood 10 ml will be collected to assess MRD by digital array assay analysis on a monthly basis for up to 6 months In addition bone marrow aspirate will be collected at approximately Month 3 and 6 following SCT for assay analysis Patient medical records will be reviewed 6 and 12 months after completing their last MRD follow up assessment to confirm survival status remission status and gather information related to relapse
Detailed Description:
Minimal residual disease MRD refers to the presence of cancer cells that are present after therapy and not otherwise detectable by clinical findings including standard clinical assays and radiographic imaging Detection of MRD before it becomes clinically detectable provides an opportunity to intervene and optimize treatment with the possibility of curing more patients For the above reasons detection of MRD through evaluation of blood-based biomarkers represents a promising area to improve clinical outcomes in patients with a variety of solid and liquid tumors In liquid tumors such as acute lymphoblastic leukemia ALL MRD assessment is already part of routine clinical practice MRD is strongly correlated with risk for relapse in ALL and MRD assessment during and after induction therapy is one of the most informative prognostic markers available For these reasons the National Comprehensive Cancer Network NCCN Guidelines Version 22020 indicate that MRD assessment is an essential component of patient evaluation over the course of sequential therapy for ALL and there are 250 references to MRD in the pediatric and adult ALL NCCN Guidelines In AML MRD assessment is routinely used in academic medical centers MRD is also strongly associated with risk of relapse in AML and MRD status is a strong independent predictor of overall survival after completion of therapy The AML NCCN Guidelines Version 32020 indicate the undeniable need for monitoring but further refinements are needed to make MRD monitoring in patients with AML more reliable In this study we will apply a new highly multiplexed digital PCR technology digital array PCR daPCR for evaluation of MRD in AML that will improve MRD assay reliability while reducing costs and time-to-results
Currently methods for MRD assessment in AML include flow cytometry for the detection of aberrant immunophenotypes as well as molecular PCR- and next generation sequencing NGS-based assays for detecting recurrent AML-associated genetic abnormalities Both flow and molecular MRD assessment have much higher sensitivity than morphologic assessment alone with flow cytometry having a lower limit of detection between 10-4 to 10-5 and molecular methods between 10-3 for NGS methods to 10-5 for PCR-based methods Each of the current methods have major limitations that prevent broader adoption in AML Standard NGS-based methods have insufficient sensitivity and high costs Flow cytometry is a technically difficult method that is challenging to standardize and a subset of AML cases do not have sufficient evaluable surface markers to allow detection PCR-based methods can be very sensitive but each assay currently targets a single recurrent genetic abnormality eg PMLRARA fusion in acute promyelocytic leukemia and many AML cases do not have genetic abnormalities that are targeted by current clinical assays In contrast the daPCR technology we propose to apply in this study provides a high throughput multiplexed platform 24-96 variants with unprecedented dynamic range 108 high ease of use low cost and rapid turnaround time Because the daPCR can simultaneously probe for multiple variants we estimate that our initial assay will have the potential to detect and quantify the abundance of at least one AML associated mutation in 80 of AML samples This technological advance would provide a real-world solution to enable frequent deep monitoring of therapeutic response in patients with AML
Currently methods for MRD assessment in AML include flow cytometry for the detection of aberrant immunophenotypes as well as molecular PCR- and next generation sequencing NGS-based assays for detecting recurrent AML-associated genetic abnormalities Both flow and molecular MRD assessment have much higher sensitivity than morphologic assessment alone with flow cytometry having a lower limit of detection between 10-4 to 10-5 and molecular methods between 10-3 for NGS methods to 10-5 for PCR-based methods Each of the current methods have major limitations that prevent broader adoption in AML Standard NGS-based methods have insufficient sensitivity and high costs Flow cytometry is a technically difficult method that is challenging to standardize and a subset of AML cases do not have sufficient evaluable surface markers to allow detection PCR-based methods can be very sensitive but each assay currently targets a single recurrent genetic abnormality eg PMLRARA fusion in acute promyelocytic leukemia and many AML cases do not have genetic abnormalities that are targeted by current clinical assays In contrast the daPCR technology we propose to apply in this study provides a high throughput multiplexed platform 24-96 variants with unprecedented dynamic range 108 high ease of use low cost and rapid turnaround time Because the daPCR can simultaneously probe for multiple variants we estimate that our initial assay will have the potential to detect and quantify the abundance of at least one AML associated mutation in 80 of AML samples This technological advance would provide a real-world solution to enable frequent deep monitoring of therapeutic response in patients with AML
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None