Clinical trial NCT06301425: MRD Response-adapted Allo-HSCT for Adverse-risk AML
Official title: Measurable Residual Disease Response-adapted Allogeneic Hematopoietic Stem Cell Transplantation for Adverse-risk Acute Myeloid Leukemia: an Open-label, Randomized, Controlled Trial（TROPHY-AML01）
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Myeloid Leukemia
Keywords: Acute myeloid leukemia
Allogeneic hematopoietic stem cell transplantation
Measurable residual disease
Adverse risk
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Ruijin Hospital
name: Wuhan TongJi Hospital
name: Anhui Provincial Hospital
First posted: 2024-03-08
Enrollment: 178
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This TROPHY-AML01 regimen aims to identify the effectiveness and safety of MRD response-adapted allo-HSCT for adverse-risk acute myeloid leukemia in an open-label, randomized, controlled trial.

Detailed description: 1.1 Relapse is the most important cause of transplant failure Acute myeloid leukemia is one the most important hematologic malignancies for adults. According to the criteria of European LeukemiaNet (ELN) 2022, approximately 40%-50% of AML patients were categorized into adverse-risk group. The clinical outcomes of these patients receiving chemotherapy alone is poor and the 4-year probability of leukemia-free survival (LFS) after therapy is nearly 10%. Thus, allogeneic hematologic stem cell transplantation (allo-HSCT) is considered as the critical consolidation in adverse-risk AML patients, and many AML patients could achieve long-term LFS after allo-HSCT. However, nearly one third of the adverse-risk AML patients would experience relapse after allo-HSCT, and the outcomes of patients with post-transplant are very poor and relapse is also the most important cause of mortality after allo-HSCT. Thus, how to prevent post-transplant relapse is important to further improve the survival of patients with adverse-risk AML.

1.2 Measurable residual disease (MRD) can predict the relapse of AML after treatment.

The detection of MRD is one of the most important methods for defining the depth of remission. Using current sensitive techniques, the presence of 1 residual leukemia cell in 10 000-1 000 000 cells can be detected in patients with morphological complete remission (CR). The most commonly used method for MRD assessment involves (1) the determination of leukemia-associated immunophenotypic patterns (LAIPs) using multiparameter flow cytometry (MFC) and (2) the quantitative polymerase chain reaction (qPCR)-based evaluation of expression levels of leukemia-related genes, such as recurrent genetic abnormalities and other mutation types.

1.3 Pre-transplant MRD can predict the relapse of AML after allo-HSCT. MFC is one of the most common methods for MRD monitoring and is the most important method for MRD monitoring for those without leukemia-specific molecular markers. In the systemic review of Buckley et al., pre-transplant MRD was associated with worse LFS (hazard ratio \[HR\] = 2.76 \[1.90-4.00\]), overall survival (OS, HR = 2.36 \[1.73-3.22\]), and cumulative incidence of relapse (HR = 3.65 \[2.53-5.27\]).

1.4 The prognostic value of pre-transplant MRD positivity is controversial in adverse-risk AML.

Pre-transplant MRD positivity could predict relapse after allo-HSCT, however, its prognostic value may be more significantly in patients with favorite- and intermediate-risk group. Some authors suggested that pre-transplant MFC MRD was less important in predicting relapse than variables reflecting the biology of the disease (e.g., cytogenetics, molecular marker, or chemotherapy refractory). Receiving repeated consolidation to achieve pre-transplant MRD negativity may not decrease the risk of relapse and improve survival, and patients may experience relapse during consolidation chemotherapy and may suffer additional therapeutic toxicities which may increase the risk of non-relapse mortality after allo-HSCT.

Eligibility criteria: Inclusion Criteria:

1. Newly diagnosed AML;
2. Categorized into adverse-risk group according to ELN 2022 criteria;
3. 16-65 years of age at the time of diagnosis;
4. achieving CR after 1 or 2 courses of induction chemotherapies;

4) ECOG PS score of 0 to 1 5) It needs consent from the patients or/and legal guardian, and signature on the Informed Consent.

Exclusion Criteria:

1. Newly diagnosed AML, but categorized into favorite- or intermediate-risk group according to ELN 2022 criteria;
2. \< 16 years, or older than 65 years at the time of diagnosis;
3. Achieving CR after 3 or more courses of induction chemotherapies, or could not achieve CR after induction chemotherapies;
4. ECOG PS score of 2 or more;
5. Patients with other comorbidities or mental diseases that influence the life safety and compliance of patients as well as affect informed consent, enrollment in the research, follow-up visit or result interpretation.

Primary outcomes:
measure: Event-free survival (EFS)
timeFrame: 1 year
Secondary outcomes:
measure: Relapse
timeFrame: 1 year
measure: Leukemia-free survival (LFS)
timeFrame: 1 year
measure: Non-relapse mortality (NRM)
timeFrame: 1 year
measure: Overall survival (OS)
timeFrame: 1 year
measure: Acute graft-versus-host disease (aGvHD)
timeFrame: 1 year
measure: Chronic graft-versus-host disease (cGvHD)
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
Study officials:
affiliation: Peking University People's Hospital
name: Xiaodong Mo
role: PRINCIPAL_INVESTIGATOR
References: