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

Withdrawn

• Conditions: MDS; Acute Leukemia; Myelodysplastic Syndromes; AML
• Interventions: Diagnostic Test: droplet digital PCR

• Registration Number: NCT03138395
• Lead Sponsor: University of Florida

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-04-25
• Study First Submitted QC: 2017-04-28
• Study First Posted: 2017-05-03
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-29
• Last Update Posted: 2017-08-31
• Study Start: 2017-09-15
• Primary Completion: 2018-02-15
• Study Completion: 2019-08-15

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Experimental: Specimen Collection	droplet digital PCR	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.

Primary Outcome Measures

Name	Time	Method
Number of Myeloid Mutations	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Number of Myeloid Mutations in circulating DNA tumor (ctDNA) mutations	1 year	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.
Mutant Allele Frequency (MAF) Ratio	1 year	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.