iCare3: Monitoring Circulating Cancer DNA After Chemotherapy in MDS and AML (iCare3)

Predicting Disease Relapse by Monitoring Circulating Cancer DNA After Chemotherapy in Patients With MDS and AML

This study will use droplet digital PCR (ddPCR) method to quantify and track peripheral blood plasma mutant allele frequency (MAF) in MDS and AML patients before, during and after chemotherapy treatment. Quantification of MAF from fingersticks and saliva samples will also be performed to determine feasibility of obtaining adequate circulating tumor DNA (ctDNA) for ddPCR.

Study Overview

• Status: Withdrawn
• Conditions: Myelodysplastic Syndromes; AML; Acute Leukemia; MDS
• Intervention / Treatment: Diagnostic test: droplet digital PCR

Detailed Description

The greatest challenge in cancer is relapsed disease. Despite best available therapies, approximately 20% of acute myeloid leukemia (AML) patients and 80% of myelodysplastic syndrome (MDS) patients die of relapsed disease. Minimal residual disease (MRD) is the main predictor of refractory disease following chemotherapy. In AML and MDS patients, mutant allele frequency (MAF) associates with future occurrence of relapse. Current oncology practice relies on painful bone marrow biopsies and light microscopy to monitor disease progression, remission, and relapse. Because of the bias in disease sampling and low sensitivity testing, there is an urgent need for a higher sensitivity test to monitor the tumor burden in these patients. The Investigator developed a rapid and ultrahigh sensitivity method to detect cancer-associated mutant alleles. This study will use our droplet digital PCR (ddPCR) method to quantify and track peripheral blood plasma MAF in MDS and AML patients before, during and after chemotherapy treatment. Quantification of MAF from fingersticks and saliva samples will also be performed to determine feasibility of obtaining adequate circulating tumor DNA (ctDNA) for ddPCR. Results from this project will generate a non-invasive means to monitor cancer response and progression months before current clinical methods, and provide an opportunity to intervene before the patient relapses. Furthermore, establishing a quantitative method to measure cancer burden will empower clinical researchers to measure biological activity in phase II and III clinical trials of new therapeutic agents.

• Study Type: Observational

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

AML and MDS patients who have already consented or prospectively consent to participate on iCare for Cancer (IRB 201500073) and the Malignant Hematology Bank (IRB 201501063) to participate in this study.

Description

Inclusion Criteria:

• Clinical diagnosis of MDS or AML;
• Have previously consented or prospectively consent to participate in iCare for Cancer (IRB201500073) and the Malignant Hematology Bank (IRB201501063); and
• Must be 18 years of age or older.

Exclusion Criteria:

• Have not previously consented or prospectively consent to participate in iCare for Cancer (IRB201500073) and the Malignant Hematology Bank (IRB201501063); and
• Must be 100 years of age or less.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Experimental: Specimen Collection; Collection of peripheral blood and bone marrow samples will occur during routine care procedures. Collection of finger stick and saliva specimens will occur on the same day as the peripheral blood and bone marrow procedure, or during routine clinical procedures.

Diagnostic test: droplet digital PCR; This study will use our droplet digital PCR (ddPCR) method to quantify and track peripheral blood plasma MAF in MDS and AML patients before, during and after chemotherapy treatment. Quantification of MAF from fingersticks and saliva samples will also be performed to determine feasibility of obtaining adequate circulating tumor DNA (ctDNA) for ddPCR. Results from this project will generate a non-invasive means to monitor cancer response and progression months before current clinical methods, and provide an opportunity to intervene before the patient relapses.; Other Names: ddPCR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Myeloid Mutations	To count the number of myeloid mutations with the use of a droplet digital PCR (ddPCR) method which will quantify and track peripheral blood plasma, finger stick blood sample, and saliva mutant allele frequency (MAF) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients before, during and after chemotherapy treatment.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Myeloid Mutations in circulating DNA tumor (ctDNA) mutations	To count the number myeloid mutations in ctDNA through the collection of serial samples from AML and MDS patients to determine minimal residual disease (MRD) or relapse free survival.	1 year
Mutant Allele Frequency (MAF) Ratio	To count the overall number of finger stick and saliva ctDNA MAF and compare it to the overall number of peripheral blood and bone marrow MAF.	1 year

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Leylah Drusbosky, PhD, University of Florida

Study record dates

Study Major Dates

• Study Start (Anticipated): September 15, 2017
• Primary Completion (Anticipated): February 15, 2018
• Study Completion (Anticipated): August 15, 2019

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: April 28, 2017
• First Posted (Actual): May 3, 2017

Study Record Updates

• Last Update Posted (Actual): August 31, 2017
• Last Update Submitted That Met QC Criteria: August 29, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: relapse; PCR; acute myeloid leukemia; myelodysplastic syndrome; polymerase chain reaction; droplet digital
• Additional Relevant MeSH Terms: Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: IRB201700351; iCare3 (Other Identifier: University of Florida); 15963 (Other Identifier: University of Florida)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No