Acute Myeloid LeukemiaNCT03488862
Pilot Evaluation of a Microfluidic Assay to Detect Minimal Residual Disease and Predict Relapse in AML Patients
An observational study of Acute Myeloid Leukemia, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Acute Myeloid Leukemia
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2018to 28 Oct 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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).
Who may be able to join
- 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) at the NCCH are eligible. These subjects must provide written informed consent to participate.
- --For the purposes of this study, induction chemotherapy is any therapy intended to induce remission in AML patients that combines anthracycline/anthracenedione with cytarabine; or combinations of cytarabine at a dose of ≥1 g/m2/dose x ≥ 5 doses with a purine analogue. Liposomal combinations of anthracycline and cytarabine are also considered induction therapy. Subjects receiving investigational induction therapies will be eligible as long as the standard-of-care agents within the induction therapy fulfills criteria above.
- For the purposes of this study, specific choice of consolidation chemotherapy, or decision to pursue SCT in remission are not mandated prior to enrollment, as these decisions are not typically made until after induction chemotherapy has been given.
- Subjects scheduled for SCT or ICC must have confirmed CD33-, CD34-, CD117- or CD123-positive disease to qualify for enrollment to undergo serial blood draws for assessment of MRD by microfluidic chip analysis.
- Subjects may be enrolled after beginning induction chemotherapy, provided that sufficient AML blasts are available in the pre-treatment peripheral blood or bone marrow sample to confirm that the blasts express CD33, CD34, CD117 or CD123.
Who cannot join
- Adult patients (≥18 years of age) with newly diagnosed or suspected AML who are scheduled to undergo SCT or ICC at the NCCH who do not provide written informed consent to participate are ineligible.
- Patients who are receiving non-intense therapies for AML that do not contain anthracycline/anthracenedione or dual analog therapies. Such non-intense therapies include: DNA methyltransferase inhibitors (azacitidine/decitabine), combinations including DNA methyltransferase inhibitors, cytarabine monotherapy at doses below 1 g/m2 x 5, purine analog monotherapy or investigational therapies that are not combined with standard induction agents.
- Subjects who test negative for the leukemic blasts surface antigens CD33, CD34, CD117, and CD123 are ineligible for inclusion to undergo serial blood draws for assessment of MRD by microfluidic chip analysis.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot Evaluation of a Microfluidic Assay to Detect Minimal Residual Disease and Predict Relapse in Acute Myeloid Leukemia (AML) Patients in Remission Following Allogeneic Stem Cell Transplant or Induction and Consolidation Chemotherapy
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.
Read the 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.
- Conditions
- Acute Myeloid Leukemia
- Medical subject headings
- Leukemia, Myeloid, Acute
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of rising Minimal Residual Disease
The number of detected AML cells will be recorded for each obtained blood sample. An indicator of relapse is when the number of AML cells exceeds the threshold pre-specified before the study. The goal is to evaluate the sensitivity and specificity of the device against clinically confirmed relapse.
Measured: The study will enroll 40 subjects with newly diagnosed or suspected AML or those who are transplant eligible. Subjects with confirmed remission after induction chemotherapy or after SCT will be followed for 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2018
- Study start1 Mar 2018
- Primary completion28 Oct 2020
- Study completion28 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Armistead, MD, Principal investigator, UNC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03488862
- Sponsor's protocol ID
- LCCC 1702
- Status last verified
- Jan 2021
- First submitted
- 28 Mar 2018
- Last updated
- 13 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Evaluation of a Microfluidic Assay to Detect Minimal Residual Disease and Predict Relapse in Acute Myeloid Leukemia (AML) Patients in Remission Following Allogeneic Stem Cell Transplant or Induction and Consolidation Chemotherapy
- ClinicalTrials.gov ID
- NCT03488862
- Acronym / sponsor ID
- LCCC 1702
- Conditions
- Acute Myeloid Leukemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 28 Oct 2020 (actual)
- Study completion
- 28 Oct 2020 (actual)
- First posted
- 5 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (5 listed)
- 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) at the NCCH are eligible. These subjects must provide written informed consent to participate.
- --For the purposes of this study, induction chemotherapy is any therapy intended to induce remission in AML patients that combines anthracycline/anthracenedione with cytarabine; or combinations of cytarabine at a dose of ≥1 g/m2/dose x ≥ 5 doses with a purine analogue. Liposomal combinations of anthracycline and cytarabine are also considered induction therapy. Subjects receiving investigational induction therapies will be eligible as long as the standard-of-care agents within the induction therapy fulfills criteria above.
- For the purposes of this study, specific choice of consolidation chemotherapy, or decision to pursue SCT in remission are not mandated prior to enrollment, as these decisions are not typically made until after induction chemotherapy has been given.
- Subjects scheduled for SCT or ICC must have confirmed CD33-, CD34-, CD117- or CD123-positive disease to qualify for enrollment to undergo serial blood draws for assessment of MRD by microfluidic chip analysis.
- Subjects may be enrolled after beginning induction chemotherapy, provided that sufficient AML blasts are available in the pre-treatment peripheral blood or bone marrow sample to confirm that the blasts express CD33, CD34, CD117 or CD123.
Key exclusion criteria (3 listed)
- Adult patients (≥18 years of age) with newly diagnosed or suspected AML who are scheduled to undergo SCT or ICC at the NCCH who do not provide written informed consent to participate are ineligible.
- Patients who are receiving non-intense therapies for AML that do not contain anthracycline/anthracenedione or dual analog therapies. Such non-intense therapies include: DNA methyltransferase inhibitors (azacitidine/decitabine), combinations including DNA methyltransferase inhibitors, cytarabine monotherapy at doses below 1 g/m2 x 5, purine analog monotherapy or investigational therapies that are not combined with standard induction agents.
- Subjects who test negative for the leukemic blasts surface antigens CD33, CD34, CD117, and CD123 are ineligible for inclusion to undergo serial blood draws for assessment of MRD by microfluidic chip analysis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Assessment of rising Minimal Residual Disease
Time frame: The study will enroll 40 subjects with newly diagnosed or suspected AML or those who are transplant eligible. Subjects with confirmed remission after induction chemotherapy or after SCT will be followed for 1 year.
The number of detected AML cells will be recorded for each obtained blood sample. An indicator of relapse is when the number of AML cells exceeds the threshold pre-specified before the study. The goal is to evaluate the sensitivity and specificity of the device against clinically confirmed relapse.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Armistead, MD principal investigator
UNC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Myeloid Leukemia, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of rising Minimal Residual Disease (time frame: The study will enroll 40 subjects with newly diagnosed or suspected AML or those who are transplant eligible. Subjects with confirmed remission after induction chemotherapy or after SCT will be followed for 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2021.