Assessment of Measurable Residual Disease in Allo-HSCT Using Digital Polymerase Chain Reaction

Predicting Patient Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: A Comparison of Measurable Residual Disease (MRD) Assessment by Digital Polymerase Chain Reaction and Conventional MRD

A research investigation into the efficacy of digital Polymerase Chain Reaction (dPCR) for monitoring measurable residual disease (MRD) during allogeneic hematopoietic stem cell transplantation, with a focus on predicting relapse in patients diagnosed with leukemia, myelodysplastic syndromes (MDS), and related hematological conditions.

Study Overview

• Status: Recruiting
• Conditions: Acute Leukemia; MDS; CML; MDS/MPN
• Intervention / Treatment: Diagnostic test: Digital PCR; Diagnostic test: Quantitative PCR; Diagnostic test: MFC

Detailed Description

This prospective clinical study focuses on patients diagnosed with leukemia, myelodysplastic syndromes (MDS), and related hematological conditions post-allogeneic hematopoietic stem cell transplantation. The primary objective is to assess the efficacy of digital Polymerase Chain Reaction (dPCR) in monitoring measurable residual disease (MRD), including markers such as BCR::ABL, KMT2A, etc., as compared to other MRD monitoring methods such as conventional quantitative PCR or multicolor Flow Cytometry (MFC). Key endpoints include the recurrence of MRD using conventional methods, hematological relapse, disease-free survival, overall survival, and non-relapse mortality.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Meng Lv, M.D,Ph.D; Phone Number: +861088324637; Email: drlvmeng@163.com
• Study Contact Backup: Name: Ya-zhen Qin, Ph.D; Phone Number: +861088324702; Email: qin2000@aliyun.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Zi-qi Han, BS; Phone Number: +861088324577; Email: ncrch_pku@163.com
      • Principal Investigator: Xiao-jun Huang
      • Sub-Investigator: Meng Lv, M.D, Ph.D
      • Sub-Investigator: Ya-zhen Qin, Ph.D
      • Sub-Investigator: Xiao-su Zhao, M.D,Ph.D
      • Sub-Investigator: Jing Liu, M.D,Ph.D
      • Sub-Investigator: Ying-jun Chang, M.D,Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with hematological malignancies who underwent allo-HSCT were enrolled for MRD monitoring peri-HSCT

Description

Inclusion Criteria:

• The presence of at least one fusion gene or hematological tumor-associated mutation detected at diagnosis by NGS or real-time PCR provided for posttransplant MRD monitoring.
• Neutrophil engraftment
• Received at least one MRD monitoring by digital PCR after HSCT

Exclusion Criteria:

• Patients who relapsed or died before the first digital PCR monitoring
• Patients only with mutations in DNMT3A, TET2, and ASXL1 ("DTA mutations") or only germline mutations

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acute Leukemia; Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Mixed Phenotype Acute Leukemia	Diagnostic test: Digital PCR; digital Polymerase Chain Reaction (dPCR); Diagnostic test: Quantitative PCR; Real-time Polymerase Chain Reaction (real-time PCR); Diagnostic test: MFC; Multicolor Flow Cytometry
MDS or MDS/MPN; Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, and other subtypes of Myelodysplastic/Myeloproliferative Neoplasm	Diagnostic test: Digital PCR; digital Polymerase Chain Reaction (dPCR); Diagnostic test: Quantitative PCR; Real-time Polymerase Chain Reaction (real-time PCR); Diagnostic test: MFC; Multicolor Flow Cytometry
CML; Chronic Myeloid Leukemia	Diagnostic test: Digital PCR; digital Polymerase Chain Reaction (dPCR); Diagnostic test: Quantitative PCR; Real-time Polymerase Chain Reaction (real-time PCR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Threshold of dPCR to predict conventional MRD	To establish an optimal threshold for digital PolyTo establish an optimal threshold for digital Polymerase Chain Reaction (dPCR) in predicting Measurable Residual Disease (MRD) recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MRD recurrence is defined as the reappearance or elevation of minimal residual disease, as assessed by other MRD monitoring methods such as conventional quantitative PCR or multi-color Flow Cytometry (MFC), which served as indications of pre-emptive intervention by current consensus or guideline.	2-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of relapse (CIR)	The interval from the transplantation date to hematological recurrence	2-year
Overall survival (OS)	The time from HSCT to the Death from any cause	2-year
Relapse-free survival (RFS)	The time from the date of HSCT to the occurrence of any of the following: Death from any cause Disease recurrence	2-year
Non-Relapse Mortality(NRM)	The time from the date of HSCT to deaths that result from complications other than a relapse of the underlying disease.	2-year

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Xiao-jun Huang, M.D, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 8, 2024
• First Posted (Estimated): January 18, 2024

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: leukemia; allo-HSCT; MRD; dPCR
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm, Residual
• Other Study ID Numbers: 2021PHA154-001

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