BN104 maintenance after allogeneic stem cell transplant for acute leukemia

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

This trial tests whether taking the oral menin inhibitor BN104 can reduce relapse in people with acute leukemia who have specific genetic changes and are 1–6 months after an allogeneic stem cell transplant.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07101497 on ClinicalTrials.gov

What this trial studies

This is an open‑label, single‑arm Phase 2 trial giving BN104 orally at 100–200 mg twice daily in 28‑day cycles for up to 24–36 cycles to people with acute myeloid, lymphoblastic, or ambiguous leukemia who harbor menin‑dependent genetic alterations. Eligible participants are screened and begin therapy 30–180 days after allogeneic hematopoietic stem cell transplantation, must be in complete hematologic remission with recovered counts and full donor chimerism. The primary endpoint is the two‑year relapse‑free survival rate from enrollment; secondary endpoints include overall survival, event‑free survival, cumulative relapse incidence, non‑relapse mortality, GVHD incidence, and safety. The study aims to determine whether BN104 can extend remission duration when used as post‑transplant maintenance in this high‑risk molecular subgroup.

Who should consider this trial

Good fit: Ideal candidates are people aged 12 or older (≥35 kg) with AML, ALL, or ambiguous acute leukemia in complete hematologic remission who harbor menin‑dependent alterations (for example KMT2A rearrangements, NUP98 rearrangements, or NPM1 mutation without FLT3 co‑mutation), are 30–180 days post allogeneic HSCT with full donor chimerism and adequate blood counts.

Not a fit: Patients without the specified menin‑dependent genetic alterations, those not in complete remission, those who are too early (<30 days) or too late (>180 days) after transplant, or those without adequate blood count recovery are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, BN104 could lower the chance of relapse and extend relapse‑free survival after allo‑HSCT for patients with menin‑dependent genetic alterations.

How similar studies have performed: Other menin inhibitors have shown promising remission activity in relapsed or refractory cases with KMT2A fusions, but using BN104 specifically as post‑HSCT maintenance is a novel approach that has not been proven yet.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (RECRUITING)

Study contacts

• Principal investigator: Su-ning Chen, M.D. — (0086)13814881746
• Study coordinator: Su-ning Chen, M.D.

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