This is a phase 2, open label, single arm trial. This study aims to assess the efficacy and safety of menin inhibitor BN104 as maintenance therapy in patients with acute leukemia harboring specific genetic alterations who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Eligible patients will be screened at 30-180 days post allo-HSCT. Participants will take BN104 100-200mg orally, twice a day, 28 days a cycle for 24-36 cycles. The primary endpoint is 2-year relapse-free survival rate since enrollment. The secondary endpoints included overall survival, event-free survival, cumulative incidence of relapse, non relpase related mortality and safety.
Male or female patients.
Adult and adolescent patients aged ≥12 years who must weight ≥35 kg.
Diagnosed with acute myeloid leuekmia, acute lymphoblastic leukemia or ambiguous acute leukemia according to the World Health Organization classification of hematologic neoplams (WHO 2022).
Intermediate or high risk accroding to the ELN risk stratification.
Complicated with active and uncontrolled infections.
Activation of virus, (e.g., CMV viremia with CMV DNA copies > 400 copies/ml, EBV viremia with EBV DNA copies > 400 copies/ml, and proof of activation of adenovirus and Human Parvovirus B19 ).
Activation of hepatitis B, hepatitis C, or human immunodeficiency virus.
Cardiac disease as followings: a. inherited long QT syndrome. b. Congestive heart failure with NYHA ≥ grade 2.
Single group
BN104 monotherapy
DrugBN104 will be started at 200 mg or 300mg, to a target dose of 400mg, twice daily, orally, 28 days a cycle, for a total of 24 to 36 cycles . When used in combination with posaconazoles and voriconazole, the dose of BN104 should be reduced by 50%.
2-year rate of RFS
It is measured as the proportions of numbers of patients with hematologic relapse to the numbers of the overall enrolled patients at 2 years from the first day of taking BN104 post allo-HSCT.
OS
Overall survival (OS): It is measured from the date of the first day of taking BN104 post allo-HSCT to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.
EFS
Event-freesurvival: It is measured from he date from the first day of taking BN104 post allo-HSCT to the first documented hematologic relapse, initiation of other maintenance therapy stragies such as hypomethylation agents, interferon, donor lymphocyte infusion, Bcl-2 inhibitor or death from any cause. Patients who die without evidence of relapse are typically censored at the last disease-free assessment.
CIR
Cumulative incidence of relapse (CIR): It is measured as the estimated rate of hematologic relapse or extramedullary relapse since the first day of taking BN104 post allo-HSCT.
NRM
non-relapse mortality (NRM): It is measured the probability of death attributable to treatment-related complications or comorbidities, excluding disease relapse/progression since the first day of taking BN104 post allo-HSCT.
Pre-/post-transplant MRD dynamics
Serial monitoring results of measurable residual disease status detected by qPCR or Ig/TR rearrangements since the first day of taking BN104
Impact of BN104 on immune recovery
Serial monitoring results of Immunoglobulin levels, T-cell subsets or cytokine profiling since the first day of taking BN104 post allo-HSCT.
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