Digital PCR monitoring of residual AML after allogeneic stem-cell transplant in patients with clonal hematopoiesis

Digital PCR-Based Detection of CHIP and MR Mutations for Minimal Residual Disease Monitoring After Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Acute Myeloid Leukemia

This will test whether personalized digital PCR can find tiny amounts of leukemia after allogeneic stem-cell transplant in AML patients who have clonal hematopoiesis or myelodysplasia-related mutations.

Quick facts

• Study type: Observational
• Enrollment: 100 (estimated)
• Sex: All
• Sponsor: Peking University People's Hospital (Academic / other)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07500441 on ClinicalTrials.gov

What this trial studies

This prospective observational study creates individualized digital PCR (dPCR) assays to sensitively track patient-specific mutations in AML patients after allogeneic hematopoietic stem cell transplantation. Bone marrow samples are collected at predefined time points during the first 12 months post-transplant (baseline and months 1, 2, 3, 4.5, 6, 9, and 12) for longitudinal quantification of mutation burden. The study will analyze MRD dynamics measured by dPCR against clinical outcomes including relapse, relapse-free survival, and overall survival, and compare timing of molecular relapse detection to conventional methods. The focus is on patients with clonal hematopoiesis or myelodysplasia-related gene mutations who lack common fusion genes and NPM1 mutations, a group with limited MRD options today.

Who should consider this trial

Good fit: Ideal candidates are AML patients undergoing allogeneic HSCT who are negative for common fusion genes and NPM1 but have clonal hematopoiesis or myelodysplasia-related gene mutations documented by prior NGS.

Not a fit: Patients with recurrent fusion genes or NPM1 mutations, or those whose mutation profiles cannot support a dPCR assay with sensitivity of 0.1% or better, are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this approach could enable earlier, more sensitive detection of molecular relapse after transplant and support timelier clinical interventions to prevent full relapse.

How similar studies have performed: Digital PCR and other ultra-sensitive molecular assays have shown promise for MRD detection in specific AML subtypes, but using patient-specific dPCR for clonal hematopoiesis/MR gene monitoring after allo-HSCT is relatively novel with limited dedicated outcome data to date.

Eligibility criteria

Inclusion Criteria:

1. Diagnosis of acute myeloid leukemia (AML).
2. Undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the investigating center.
3. Negative for recurrent fusion genes routinely monitored in the clinical laboratory, including but not limited to AML1::ETO, CBFB::MYH11, KMT2A (MLL) rearrangements, NUP98::NSD1, NUP98::HOXA9, FUS::ERG, DEK::NUP214, SET::NUP214, PICALM::AF10, and BCR::ABL1.
4. Availability of next-generation sequencing (NGS) results at initial diagnosis with accessible original reports.
5. Negative for NPM1 mutations at initial diagnosis.
6. Presence of clonal hematopoiesis (CH) and/or myelodysplasia-related (MR) gene mutations at initial diagnosis, including but not limited to DNMT3A, TET2, ASXL1, SRSF2, SF3B1, U2AF1, JAK2, IDH2, BCOR, EZH2, RUNX1, STAG2, and ZRSR2.

Exclusion Criteria:

1. Patients with mutation profiles unsuitable for the design of patient-specific digital PCR (dPCR) assays achieving a sensitivity of ≤0.1%.
2. Absence of evaluable molecular targets for longitudinal MRD monitoring.

Where this trial is running

Beijing, Beijing Municipality

• Peking University People's Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Ya-zhen Qin, Ph.D — Peking University People's Hospital
• Study coordinator: Meng Lv, M.D,Ph.D

Conditions Acute Myeloid Leukemia; Measurable Residual Disease; Digital PCR; Allogeneic Hematopoietic Stem Cell Transplantation; Clonal Hematopoiesis