Pilot Evaluation of a Microfluidic Assay to Detect Minimal Residual Disease and Predict Relapse in AML Patients
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasm, Residual
Study type: Observational

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.
    

Detailed 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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Adult patients (≥18 years of age) with newly diagnosed or suspected AML who are going to
        undergo stem cell transplant (SCT) or are being treated with induction and consolidation
        chemotherapy (ICC).
      
Biospecimen description: 
      Residual blood samples may be stored by the sponsor as backup to be used to confirm
      downstream assays using staining, fluorescence-activated cell sorting (FACS).