Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03488862 |
Other study ID # |
LCCC 1702 |
Secondary ID |
|
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
March 1, 2018 |
Est. completion date |
October 28, 2020 |
Study information
Verified date |
January 2021 |
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 microfluidics 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) or
Induction and Consolidation Chemotherapy (ICC) at the North Carolina Cancer Hospital (NCCH).
Procedures (methods): A total of 40 eligible subjects will be treated per standard of care
with either SCT or induction and consolidation chemotherapy (ICC) based on the appropriate
AML treatment paradigm for their disease. Peripheral blood (10 ml) for microfluidic chip
analysis and possible Immune Monitoring Core Facility analysis will be collected along with
routine lab draws prior to SCT. Patients in remission after SCT or those with confirmed
remission by bone marrow biopsy after induction chemotherapy will be followed for 1 year; and
peripheral blood (20 ml) will be collected to assess MRD by standard methods or by
microfluidic chip analysis on a monthly basis. In addition, bone marrow biopsies will be
performed at the end of consolidation (typically 5 months from remission), and at 1-year post
remission in non-transplant patients. In transplanted patients, bone marrow biopsies will be
collected at + 30 days, + 90 days, +180 days, and +360 days after SCT.
Description:
An unmet need in the treatment of AML is earlier detection of potential relapse by monitoring
MRD. The hope is that if clinicians can pinpoint when a patient's MRD starts towards a rapid
expansion to relapse, preemptive therapies can be instituted earlier with the hope of
eliciting improved outcomes. Current methods fall short of the ability to properly monitor
MRD in individual patients. An ideal MRD assay would be easy to conduct, sensitive to low MRD
levels and suitable for frequent analysis. A significant challenge for achieving this in AML
is that unlike other leukemias, AML's interpatient heterogeneity is immense; and there is no
characteristic genetic mutation or aberrant protein expression pattern for AML patients ,
thus hindering the broad applicability of polymerase chain reaction (PCR), fluorescence
in-situ hypbridization (FISH) or multi-parameter flow cytometry (MFC) testing for MRD.
Furthermore, AML relapse is rapid and it's been calculated that 42 day sampling intervals
would be a minimum frequency needed to predict 75% of relapses during follow up after
chemotherapy or SCT.
The microfluidics assay being evaluated in this study is relatively inexpensive, broadly
applicable, as it identifies almost all (>90%) of AML cells, and easy to use. The
microfluidic chip device is constructed with antibodies immobilized within the chip that can
detect cell surface antigens commonly expressed on leukemic cells (ie, CD33, CD34, CD117, and
CD123) directly in the peripheral blood without requiring preprocessing. The captured cells
are then exposed to fluorescent antibodies targeting surface proteins that are aberrantly
expressed on AML blasts (eg CD7, CD56 etc.), and fluorescence microscopy is used to identify
captured cells that express an aberrant surface protein. The investigators have already
completed a pilot study using this technology to monitor 5 AML patients after SCT. Because
this assay required peripheral blood and not a bone marrow biopsy, 39 microfluidic tests
could be carried out compared to only 8 PCR, MFC, FISH, and/or microscopy tests. Moreover,
the frequent testing allowed us to observe signs of impending relapse earlier than the bone
marrow biopsy-based test. The investigators plan to build on our findings in this trial and
test the applicability of using the microfluidic assay for early signs of AML relapse. If
successful, the microfluidic chip assay could be employed for serial MRD evaluations both in
the post-SCT setting and in patients with AML undergoing conventional chemotherapy while
providing a venue for the detailed management of a particular patient's AML including
response to therapy and risk for disease recurrence.