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

NCT ID: NCT07101497

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-01
• Study Completion Date: 2029-12-30

Brief 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.

Detailed Description

AML with KMT2A rearrangements are grouped as a high risk subtype. Allogenic hematopoietic stem cell transplantation is the only curative strategy for this subtype. However, patients with KMT2A rearrangements have a high incidence of relapse rates. BN104 is a menin inhibitor. It has shown promising remission rates in patients with relpased or refractory patients haboring specific fusions including KMT2A rearrangements. The role of BN104 in post-HSCT maintenance therapy remains unknown.

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, incidence of acute and chronic graft versus host diseas, and safety.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BN104 maitenenace

Eligible patients will take BN104 start from 200 or 300mg, to a targent dose of 400mg, twice daily orally, 28 days for a cycle. When used in combination with posaconazoles and voriconazole, the dose of BN104 should be reduced by 50%. A total of 24 to 36 cycles of BN104 was planned.

Group Type: EXPERIMENTAL

BN104 monotherapy

Intervention Type: DRUG

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%.

Interventions

BN104 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%.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Chen Suning

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Su-ning Chen, M.D.

Role: PRINCIPAL_INVESTIGATOR

(0086)13814881746

Locations

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Su-ning Chen, M.D.

Role: CONTACT

chensuning@sina.com

(0086)13814881746

Hai-ping Dai, M.D.

Role: CONTACT

(0086)13914086271

Facility Contacts

Su-ning Chen, M.D.

Role: primary

chensuning@sina.com

+8613814881746

Other Identifiers

BN104 maintenance post-HSCT

Identifier Type: -

Identifier Source: org_study_id