RecruitingPhase 2NCT07101497

Phase 2 Trial of BN104 as Post-HSCT Maintenance in Acute Leukemia

Phase 2 Trial of Menin Inhibitor BN104 as Post Hematopoietic Stem Cell Transplantation Maintenance in Patients With Acute Leukemia

Sponsor

The First Affiliated Hospital of Soochow University

Enrollment

60 participants

Start Date

Aug 1, 2025

Study Type

INTERVENTIONAL

Conditions

Acute Leukemia Menin Inhibitors Post Hematopoietic Stem Cell Transplantation Maintenance Therapy KMT2A Rearrangement NPM1 Mutation NUP98 Gene Rearrangement

Summary

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.

Eligibility

Min Age: 12 Years

Inclusion Criteria14

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.
Harboring one of the following genetic aberrations: a. somatic NPM1 mutation (without FLT3-ITD/TKD co-mutations); b. KMT2A rearrangement/KMT2A-PTD; c. NUP98 rearrangement; d. other genetic alterations dependent on menin-KMT2A.
Received allogenic hematopoietic stem cell transplantation within 30-180 days at the initiation of BN104 maintenance therapy.
Achieved full donor chimerism and hematologic recovery, with acute neuthrophil count (ANC) ≥1.0×10⁹/L, platelets ≥75×10⁹/L (no red blood cells /platelets transfusion within 7 days, no G-CSF or GM-CSF within 72 hours).
Complete hematological remission (CHR) after first allo-SCT. CHR must be confirmed by bone marrow analysis within 14 days before entering the study (CHR criteria are: "\< 5% marrow blasts, no peripheral blasts, blood platelet count \> 75×10⁹/L, WBC count \> 3.5 G/L, ANC ≥ 1.0×10⁹/L).
No extramedullary leukemia.
Eastern Cooperative Oncology Group (ECOG) performance status score 0-2.
Adequate organ function
Provided informed consent by all patients and the guardians ( aged 12-17 years).
Written informed consent.
ECOG ≥ 2.

Exclusion Criteria10

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.
≥ grade 2 acute GVHD or ≥ grade 3 chronic GVHD which requiring systemic therapy.
Have received other maintenance therapies (e.g., hypomethylating agents, targetd drugs such as Bcl-2 inhibitors, FLT3 inhibitors, IDH1/2 inhibitors, interferon, interleukin-2, donor lymphocyte infusion and chemotherapy).
History of other malignancies which needed systemic treatment (excluding those in stable remission without maintenance therapy).
Any gastrointestinal condition that may interfere with oral drug intake or absorption (e.g., dysphagia, gastroparesis, uncontrolled chronic diarrhea, intestinal graft versus host disease.
Pregnancy, breastfeeding
Hypersensitivity to BN104.

Interventions

DRUGBN104 monotherapy

BN104 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%.