Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04920188 |
| Other study ID # |
LCCC 2103 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 28, 2021 |
| Est. completion date |
June 17, 2024 |
Study information
| Verified date |
February 2024 |
| Source |
UNC Lineberger Comprehensive Cancer Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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 2.2020, 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
3.2020, 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 (e.g.,
PML/RARA 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.
