Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06301425
Other study ID # TROPHY-AML01
Secondary ID
Status Not yet recruiting
Phase N/A
First received
Last updated
Start date May 1, 2024
Est. completion date May 1, 2028

Study information

Verified date March 2024
Source Peking University People's Hospital
Contact Xiaodong Mo
Phone 86-10-88326001
Email moxiaodong@pkuph.edu.cn
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 178
Est. completion date May 1, 2028
Est. primary completion date May 1, 2027
Accepts healthy volunteers No
Gender All
Age group 16 Years to 65 Years
Eligibility 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.

Study Design


Intervention

Other:
Intervention group
Patients in interventional group could choose one of the following treatment protocols and then receive allo-HSCT if they were CR after the second consolidation: . Venetoclax plus azacitidine: azacitidine 75mg/m2/d d1-7; venetoclax 400mg/d, d1-21; . Venetoclax plus CAG: venetoclax 400mg qd d1-14; aclacinomycin 20mg qd d1-4; cytarabine 10mg/m2 q12h subcutaneous injection d1-14; G-CSF 300µg qd d1-14; . Venetoclax plus IA: venetoclax 400mg qd d1-4; idarubicin 10mg qd d1-4; cytarabine 500mg qd d1-4; . Venetoclax plus AA: venetoclax 400mg qd d1-7; aclacinomycin 20mg qd d1-7; cytarabine 100mg/m2 qd d1-7.
Control group
Receive allo-HSCT directly without the second consolidation chemotherapy.

Locations

Country Name City State
n/a

Sponsors (4)

Lead Sponsor Collaborator
Peking University People's Hospital Anhui Provincial Hospital, Ruijin Hospital, Wuhan TongJi Hospital

Outcome

Type Measure Description Time frame Safety issue
Primary Event-free survival (EFS) EFS, defined as the time from the date of randomization to the date of MRD positivity, relapse, or death due to any cause. 1 year
Secondary Relapse Relapse, defined as the time from date of randomization to date of leukemia relapse. 1 year
Secondary Leukemia-free survival (LFS) LFS, defined as the time from the date of randomization to the date of relapse or death due to any cause. 1 year
Secondary Non-relapse mortality (NRM) NRM, defined as the time from date of randomization to date of death not preceded by leukemia relapse. 1 year
Secondary Overall survival (OS) OS, defined as the time from the date of randomization to the date of death due to any cause. 1 year
Secondary Acute graft-versus-host disease (aGvHD) aGvHD, defined as the diagnosis of any aGvHD including grade I to IV. 1 year
Secondary Chronic graft-versus-host disease (cGvHD) cGvHD, defined as the diagnosis of any cGvHD including mild, moderate, severe. 1 year
See also
  Status Clinical Trial Phase
Recruiting NCT05400122 - Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer Phase 1
Recruiting NCT04460235 - Immunogenicity of an Anti-pneumococcal Combined Vaccination in Acute Leukemia or Lymphoma Phase 4
Completed NCT03678493 - A Study of FMT in Patients With AML Allo HSCT in Recipients Phase 2
Completed NCT04022785 - PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome Phase 1
Recruiting NCT05424562 - A Study to Assess Change in Disease State in Adult Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy Receiving Oral Venetoclax Tablets in Canada
Completed NCT03197714 - Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia Phase 1
Terminated NCT03224819 - Study of Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML) Early Phase 1
Active, not recruiting NCT04070768 - Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in Patients With Relapsed or Refractory CD33+ Acute Myeloid Leukemia:Big Ten Cancer Research Consortium BTCRC-AML17-113 Phase 1
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Active, not recruiting NCT04107727 - Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML) Phase 2
Recruiting NCT04385290 - Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC) Phase 1/Phase 2
Recruiting NCT04920500 - Bioequivalence of Daunorubicin Cytarabine Liposomes in Naive AML Patients N/A
Recruiting NCT03897127 - Study of Standard Intensive Chemotherapy Versus Intensive Chemotherapy With CPX-351 in Adult Patients With Newly Diagnosed AML and Intermediate- or Adverse Genetics Phase 3
Active, not recruiting NCT04021368 - RVU120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome Phase 1
Recruiting NCT03665480 - The Effect of G-CSF on MRD After Induction Therapy in Newly Diagnosed AML Phase 2/Phase 3
Completed NCT02485535 - Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant Phase 1
Enrolling by invitation NCT04093570 - A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers Phase 2
Recruiting NCT04069208 - IA14 Induction in Young Acute Myeloid Leukemia Phase 2
Recruiting NCT05744739 - Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML) Phase 1
Recruiting NCT04969601 - Anti-Covid-19 Vaccine in Children With Acute Leukemia and Their Siblings Phase 1/Phase 2