Status and phase
Conditions
Treatments
About
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.
Full description
The study is divided into 2 phases. Phase1 dose escalation part will enroll 19-42 patients to evaluate safety and tolerance of BN104 in patients with relapsed/refractory (R/R) Acute Leukemia to determine maximum tolerated dose and recommended phase2 dose (RP2D), including 10-12 patient with specific mutations (KMT2A gene rearrangement or NPM1 gene mutation) enrolled at dose optimization phase.
Phase II expansion part will enroll 30-48 patients and be conducted at the selected dose level to further evaluate the safety and tolerability of BN104, as well as preliminary efficacy in Acute leukemia subjects with specific mutations (KMT2A gene rearrangement or NPM1 gene mutation). Patients will be allocated into 3 Acute Leukemia subgroup cohorts depends on their genotype.
Laboratory tests will be performed weekly in Cycles 1-2, bi-weekly in Cycle3 and every 4weeks from Cycle 4 onwards. Efficacy assessment will be performed on baseline, C2D1, C3D1 and every 2 cycles from Cycle3 onwards. Additional clinical assessments and laboratory tests may be performed at discretion of the investigator as clinically indicated.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Have been fully informed about the study and have voluntarily signed the ICF;
patients with relapsed/refractory acute leukemia (including AML, ALL, and mixed-spectrum leukemias, except acute promyelocytic leukemia) diagnosed according to the 2022 World Health Organization (WHO) criteria, and for whom there are no superior therapeutic alternatives as assessed by the investigator, and who meet at least one of the following criteria:
Notes:
For Phase I dose-optimization and Phase II subjects, the combination of NPM1 mutation or KMT2A rearrangement should also be specified.
Age ≥ 18 years;
ECOG score 0-2;
Adequate hepatic, renal, and cardiac functions
Expected survival of more than 12 weeks as judged by the investigator
Be able to perform treatments, visits, and undergo study-related testing as required by the protocol
Female patients of childbearing potential or male patients whose female partners are of childbearing potential must agree to use an effective method of contraception, such as a double-barrier method of contraception, condoms, oral or injectable contraceptives, and intrauterine devices (IUDs), for the duration of the study and for 30 days after the last study dose. Postmenopausal women (>45 years of age and menopause for more than 1 year) and surgically sterilized women are not subject to this condition.
Exclusion criteria
definite active central nervous system (CNS) leukemia (previous CNS leukemia that has been treated and controlled, but requires screening period lumbar puncture for cerebrospinal fluid examination for confirmation, or routine receipt of standard CNS prophylaxis are acceptable);
a known history of clinically significant liver disease, including viral or other hepatitis or cirrhosis
known human immunodeficiency virus (HIV) infection;
pregnant (positive screening pregnancy test) or lactating females;
meet any of the following cardiac-related criteria:
the patient has suffered from other malignant tumors within the past 5 years, except for radically treated basal cell carcinoma of the skin, carcinoma in situ of the breast or carcinoma in situ of the cervix;
has received autologous hematopoietic stem cell transplantation (ASCT) or chimeric antigen receptor T cell (CAR T) therapy within 60 days prior to screening, or has not recovered from toxicity associated with ASCT or CAR-T therapy
allogeneic hematopoietic stem cell transplantation has been performed within 100 days prior to screening, or the patient is still comorbid with active acute or chronic graft-versus-host disease, or the patient is still in need of immunosuppressive therapy;
anti-leukemia therapy, including chemotherapy, radiotherapy, hormone therapy, or immunotherapy (excluding hydroxyurea) within 2 weeks prior to the start of study treatment;
prior participation in a clinical study of another drug less than 2 weeks or 5 half-lives for small molecules and less than 4 weeks or 5 half-lives for large molecules (e.g., antibody-based drugs) from the last dose, whichever is shorter
prior treatment with targeted menin;
prior toxic reactions to anti-leukemia therapy that have not returned to grade 0 or 1 levels (except alopecia areata)
uncontrolled active infection:
subjects with known dysphagia, short bowel syndrome, gastroparesis, or other conditions that limit oral drug intake or gastrointestinal absorption;
a history of severe allergy to menin inhibitors or hypersensitivity to any of the components of BN104
inadequate patient compliance with participation in this clinical study as judged by the investigator;
any other disease, metabolic abnormality, physical examination abnormality, or clinically significant laboratory test abnormality that, in the judgment of the investigator, gives reason to suspect that the patient has a disease or condition that is inappropriate for the use of the study medication, or that will interfere with the interpretation of the results of the study, or that places the patient at high risk.
Primary purpose
Allocation
Interventional model
Masking
90 participants in 5 patient groups
Loading...
Central trial contact
Yolin Pan
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal