A Study of BN104 in the Treatment of Acute Leukemia

NCT06052813 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BN104-101
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

The Phase I/II trial is to learn the safety, pharmacokinetics, and preliminary efficacy of BN104 taken once daily or twice daily in patients with acute lymphocytic leukemia or acute myeloblastic leukemia.

Conditions

ALL, Adult; AML, Adult; Acute Leukaemia; KMT2A Rearrangement; NPM1 Mutation; NUP98 Gene Rearrangement; Menin Inhibitors

Outcome Measures

Primary Outcomes (3)

• PhaseI Incidence of Dose Dose limiting toxicities(DLTs)

  DLTs will be evaluated at the end of cycle 1(28 days after receiving BN104) for each dose level by evaluating abnormal laboratory examinations by the Investigator.

  DLT last 28days(at the end of cycle 1 for each dose)

• PhaseI Incidence of serious adverse events(SAEs)

  SAEs will be recorded in the eCRF from time of the signing informed consent through 30 days after the last dose of BN104.

  36 month

• PhaseII efficacy assessment

  To evaluate the efficacy of BN104 in treating patients with relapsed/refractory acute leukaemia with specific mutations (KMT2A rearrangement or NPM1 mutation) by mesuring patients bone marrow blasts/immature cells(CR, CRh rate) at protocol defined efficacy assessment timepoint

  36 month

Secondary Outcomes (20)

• Phase I/II Evaluate the number and frequency of adverse events (AEs)

  36 months

• Phase I/II Evaluate patient vital signs

  36 months

• Phase I/II Evaluate electrocardiogram (ECG) assessments

  36 months

• Phase I/II pharmacokinetic Maximum concentration (Cmax)

  36 months

• Phase I/II pharmacokinetic Peak time(Tmax)

  36 months

Study Arms (9)

200mg QD

EXPERIMENTAL

The starting dose cohort(200mg QD) where accelerated titrated dose-escalation method is applied, a patient will initially receive a single dose BN104 on Day 1 of Cycle 0 (3 days prior to Day 1 of Cycle 1) to evaluate the concentration of BN104 up to 72 hours after administration and the safety of single dose of BN104. Then the patient begins continuous treatment with BN104 200 mg QD on Day 1 of Cycle 1 by every 28-day treatment cycle until disease progression, intolerable toxicity, withdrawal of consent, loss to follow-up, death, or other conditions in which patients are not suitable for study treatment, whichever occurs first.

Drug: BN104 monotherapy

200mg BID

EXPERIMENTAL

After completion of DLT evaluation for the first dose cohort (200 mg QD), patients will begin to receive twice daily (BID) dosing frequency in each 28-day treatment cycle for the subsequent dose cohorts for which conventional 3+3 design is used until disease progression, intolerable toxicity, withdrawal of consent, loss to follow-up, death, or other conditions in which patients are not suitable for study treatment, whichever occurs first.

Drug: BN104 monotherapy

400mg BID

EXPERIMENTAL

After completion of DLT evaluation for the first dose cohort (200 mg QD), patients will begin to receive twice daily (BID) dosing frequency in each 28-day treatment cycle for the subsequent dose cohorts for which conventional 3+3 design is used until disease progression, intolerable toxicity, withdrawal of consent, loss to follow-up, death, or other conditions in which patients are not suitable for study treatment, whichever occurs first.

Drug: BN104 monotherapy

600 BID

EXPERIMENTAL

After completion of DLT evaluation for the first dose cohort (200 mg QD), patients will begin to receive twice daily (BID) dosing frequency in each 28-day treatment cycle for the subsequent dose cohorts for which conventional 3+3 design is used until disease progression, intolerable toxicity, withdrawal of consent, loss to follow-up, death, or other conditions in which patients are not suitable for study treatment, whichever occurs first.

Drug: BN104 monotherapy

800 BID

EXPERIMENTAL

After completion of DLT evaluation for the first dose cohort (200 mg QD), patients will begin to receive twice daily (BID) dosing frequency in each 28-day treatment cycle for the subsequent dose cohorts for which conventional 3+3 design is used until disease progression, intolerable toxicity, withdrawal of consent, loss to follow-up, death, or other conditions in which patients are not suitable for study treatment, whichever occurs first.

Drug: BN104 monotherapy

Adolescent cohort - 400mg BID

EXPERIMENTAL

The first 3-6 patients will be dosed at 400 mg BID. If there is no significant difference in Cmax and AUC between adolescent and adult patients, and no DLT occurs in 3-6 patients or ≤1 DLT occurs in 6 patients, the dose will be escalated to 600 mg BID, and 3-6 additional adolescent patients will be enrolled. patients will begin to receive twice daily (BID) dosing frequency in each 28-day treatment cycle for the subsequent dose cohorts for which conventional 3+3 design is used until disease progression, intolerable toxicity, withdrawal of consent, loss to follow-up, death, or other conditions in which patients are not suitable for study treatment, whichever occurs first.

Drug: BN104 monotherapy

Adolescent cohort - 600mg BID

EXPERIMENTAL

patients will begin to receive twice daily (BID) dosing frequency in each 28-day treatment cycle for the subsequent dose cohorts for which conventional 3+3 design is used until disease progression, intolerable toxicity, withdrawal of consent, loss to follow-up, death, or other conditions in which patients are not suitable for study treatment, whichever occurs first. If ≤1 DLT occurs in 6 patients, at 600mg bid, then enrolment will be expanded at the 600 mg BID dose level to approximately 20 patients, for patients with relapsed/refractory acute leukaemia with KMT2A rearrangement and NPM1 mutation, ensuring at least 10 patients each with KMT2A rearrangement and NPM1 mutation in relapsed/refractory acute leukaemia at the 600 mg BID dose level.

Drug: BN104 monotherapy

Phase II CohortA - Patients with relapsed/refractory AML with NPM1 mutation

EXPERIMENTAL

receiving oral BN104 treatment at a dose of 600 mg BID (300 mg BID when co-administered with strong CYP3A4 inhibitors)

Drug: BN104 monotherapy - rp2d

Phase II Cohort B: r/r acute leukaemia with KMT2Ar (including AML, ALL, or MPL)

EXPERIMENTAL

receiving oral BN104 treatment at a dose of 600 mg BID (300 mg BID when co-administered with strong CYP3A4 inhibitors)

Drug: BN104 monotherapy - rp2d

Interventions

BN104 monotherapy DRUG

Phase I(adults): Will be administered orally once daily (approximately every 24 hours) for the first cohort or twice daily (approximately every 12 hours) for the subsequent cohorts.

200mg BID; 200mg QD; 400mg BID; 600 BID; 800 BID

BN104 monotherapy - rp2d DRUG

receiving oral BN104 treatment at a dose of 600 mg BID (300 mg BID when co-administered with strong CYP3A4 inhibitors)

Phase II Cohort B: r/r acute leukaemia with KMT2Ar (including AML, ALL, or MPL); Phase II CohortA - Patients with relapsed/refractory AML with NPM1 mutation

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Have been fully informed about the study and have voluntarily signed the ICF;
• Patients diagnosed with relapsed/refractory acute leukaemia (including AML, ALL, and mixed-phenotype acute leukaemia, excluding acute promyelocytic leukaemia) according to the World Health Organization (WHO) criteria in 2022, with bone marrow morphological changes (blasts/immature cells ≥ 5%), and who have been evaluated by the investigator to have no better treatment options, must meet at least one of the following conditions:
• Primary refractory disease, newly diagnosed disease that show no response after 2 cycles of standard treatment;
• First relapse, relapsed within 12 months after CR/CRh/CRi following consolidation/intensive therapy;
• Relapsed after 12 months and unresponsive to conventional salvage chemotherapy;
• Patients with 2 or more relapses;
• Patients intolerant to intensive chemotherapy who experience disease progression during continuous low-intensity therapy; Note: Patients with secondary AML or AML transformed from MDS, MPN, can also be enrolled, but they need to meet the above criteria after the disease has transformed into AML;
• For all Phase I patients, the presence of NPM1 mutation, or KMT2A rearrangement, or NUP98 rearrangement must be confirmed,During Phase I, patients with other acute leukemia subtypes shown to depend on menin-KMT2A interaction (e.g., UBTF-TD) or driven by HOXA/MEIS1 overexpression may also be eligible after consultation with the Sponsor's Medical Monitor;
• Patients in the Phase II (single-arm pivotal clinical study) must have a confirmed NPM1 mutation or KMT2A rearrangement. Enrollment based on local testing results is acceptable with a copy of the test report provided; however, all patients are required to submit screening bone marrow samples to the central laboratory ,Eligible NPM1 mutations include exon12 type A, B, and D mutations ; other NPM1 mutations causing cytoplasmic localization require sponsor pre-approval for enrollment. KMT2A rearrangements exclude non-fusion rearrangements involving KMT2A partial tandem duplication (KMT2A-PTD).
• Peripheral blood white blood cell count ≤ 35 × 109/L (use of hydroxyurea to control peripheral white blood cell count is permitted);
• Age ≥ 12 years (for adolescent patients aged 12 years or older but not yet 18 years old, weight must be ≥ 40 kg);
• ECOG score 0-2;
• Adequate hepatic, renal, and cardiac functions
• Expected survival of more than 12 weeks as judged by the investigator
• For patients with D-dimer test results \> 5 × ULN during screening, relevant tests (such as rechecking coagulation function after a certain interval, lower extremity deep vein ultrasound, etc.) are required to exclude deep vein thrombosis, hypercoagulation, and disseminated intravascular coagulation before enrollment;

You may not qualify if:

• Known active central nervous system (CNS) leukaemia (including imaging abnormalities and CSF smear or flow cytometry indicating leukaemia cells; prior CNS leukaemia that has been treated and controlled is acceptable, but requires screening lumbar puncture and CSF test for confirmation, or routine standard CNS prophylaxis is acceptable);
• Known history of clinically significant liver disease, including viral or other hepatitis or hepatic cirrhosis:
• Hepatitis B surface antigen (HBsAg) seropositive, requires Hepatitis B virus (HBV) DNA negative for enrollment;
• For Hepatitis C virus (HCV) antibody seropositive patients, HCV RNA negative result is required for enrollment.
• Known human immunodeficiency virus (HIV) infection;
• Pregnancy (positive pregnancy test at screening) or lactating females;
• Any of the following cardiac-related criteria is met:
• Hereditary long QT syndrome or QTcF \> 450 msec;
• Various clinically significant cardiovascular disorders, including acute myocardial infarction, unstable angina pectoris, coronary artery bypass surgery within 6 months prior to enrollment, cardiac failure congestive of New York Heart Association (NYHA) Class 2 or higher (including Class 2), etc.;
• Patient has other concomitant malignant tumours, except for:
• Curatively treated skin basal cell carcinoma, breast cancer in situ, or cervical carcinoma in situ, etc.;
• Patients with low-grade lymphoma who are in CR, asymptomatic, without large mass lesions, and do not require systemic therapy or radiotherapy;
• Other malignant tumours treated with curative intent, with CR achieved for at least 2 years, and no requirement for systemic maintenance therapy or radiotherapy;
• Received autologous haematopoietic stem cell transplant (ASCT) or Chimeric Antigen Receptor T-cell (CAR-T) therapy within 60 days prior to screening, or toxicity related to ASCT or CAR-T therapy has not yet resolved;
• Underwent allogeneic HSCT within 100 days prior to screening, or the patient still has Grade ≥ 2 acute graft versus host disease or chronic graft versus host disease requiring systemic treatment, or the patient still requires immunosuppression (prednisone ≤ 10 mg/day or equivalent dose of other corticosteroids is permissible for screening; corticosteroids need to be gradually tapered and discontinued after enrolment unless there is a specific reason);

Sponsors & Collaborators

• Institut de Recherches Internationales Servier (I.R.I.S.): lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, 215006, China

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid

Study Officials

• Depei WU, Prof.

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

• Mingyuan Sun, Dr.

  Institute of Hematology, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

• Yan Li, Dr.

  Institute of Hematology, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

• Xudong Wei, Prof.

  Henan Oncology Hospital

  PRINCIPAL INVESTIGATOR

• Dengju Li, Prof.

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

• Yuhua Li, Prof.

  Southern Medical University, China

  PRINCIPAL INVESTIGATOR

• Xiaoyu Zhu, Prof.

  Anhui Provinvcal Hospital

  PRINCIPAL INVESTIGATOR

• Fei Li, Prof.

  The First Affiliated Hospital of Nanchang University

  PRINCIPAL INVESTIGATOR

• Jinhai Ren, Prof.

  The Second Hospital of Hebei Medical University

  PRINCIPAL INVESTIGATOR

• He Huang, Prof.

  Zhejiang University

  PRINCIPAL INVESTIGATOR

• Pengcheng He, Prof.

  First Affiliated Hospital Xi'an Jiaotong University

  PRINCIPAL INVESTIGATOR

• Wei Wang, Dr.

  The Affiliated Hospital of Qingdao University

  PRINCIPAL INVESTIGATOR

• Yu Cao, Dr.

  The Affiliated Hospital of Qingdao University

  PRINCIPAL INVESTIGATOR

• Songfu Jiang, Prof.

  First Affiliated Hospital of Wenzhou Medical University

  PRINCIPAL INVESTIGATOR

• Jian Ge, Prof.

  The First Affiliated Hospital of Anhui Medical University

  PRINCIPAL INVESTIGATOR

• Bei Liu, Dr.

  LanZhou University

  PRINCIPAL INVESTIGATOR

• Yuping Gong, Prof.

  West China Hospital

  PRINCIPAL INVESTIGATOR

• Xiaojun Xu, Prof.

  Children's Hospital, Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

• Xiaofan Zhu, Prof.

  Chinese Academy of Medical Sciences Haematological Diseases Hospital

  PRINCIPAL INVESTIGATOR

• Wenting Hu, Dr.

  Shanghai Children's Medical Center

  PRINCIPAL INVESTIGATOR

• Meng LV, Dr.

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

• Jun Luo, Prof.

  First Affiliated Hospital of Guangxi Medical University

  PRINCIPAL INVESTIGATOR

• Zhenfang Liu, Prof.

  First Affiliated Hospital of Guangxi Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2023
• First Posted: September 25, 2023
• Study Start: October 19, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)