acute myeloid leukemia
Conditions
Interventions
A group (Suitable for newly treated AML patients with specific mutations receiving intensive chemotherapy):BN104 in combination with intensive induction chemotherapy or venecola/azacitidine
C group (Relapsed/refractory AML patients with specific mutations):BN104 in combination with intensive induction chemotherapy or venecola/azacitidine
B group (Newly treated AML patients >=75 years old or <75 years old with specific mutations who are not eligible for intensive chemotherapy due to co-morbiditie):BN104 in combination with intensive i
D group (Newly diagnosed AML patients with KMT2A rearrangement, NPM1 mutation, or NUP98 rearrangement and suitable for intensified therapy):BN104 is treated with a combination of RP2D induced remissio
E group (Newly diagnosed AML patients with KMT2A rearrangement, NPM1 mutation, or NUP98 rearrangement who are not suitable for intensive therapy):BN104 uses RP2D in combination with venecola/azacitidi
F group (Recurrent/refractory AML patients with KMT2A rearrangement, NPM1 mutation, or NUP98 rearrangement):BN104 uses RP2D in combination with venecola/azacitidine
Sponsors
The First Affiliated Hospital of Soochow University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Have fully understood this study and voluntarily signed ICF; 2.Patients newly diagnosed with newly treated AML (groups A and B) or relapsed/refractory AML WHO have previously been monotherapies with menin inhibitors (group C) according to World Health Organization (WHO) criteria in 2022 and stratified as having a moderate or poor prognosis according to 2022 ELN risk, It is also necessary to explicitly incorporate NPM1 mutations or NUP98 rearrangements or KMT2A rearrangements (including AFF1::KMT2A, MLLT3:: KMT2A, MLLT10:: KMT2A, TET1::KMT2A, KMT2A::ELL, AFDN:: KMT2A, KMT2A::MLLT1, KMT2A::MLLT6, etc.), KMT2A-PTD are also allowed to be enrolled (test results from the research center can be accepted for inclusion, provided that the patient provides a copy of the test report; If there is no previous test result, it is necessary to complete the test at the research center and provide a copy of the report); If there is evidence that other subtypes of AML other than the specific variants described above are also driven by HOXA or MEIS1 gene overexpression and are intermediate-high risk individuals with a moderate or poor prognosis in the 2022 ELN risk stratification, they may also be included after communication with sponsor investigators; 3.Peripheral blood white blood cell count =18 years; 5.Eastern Oncology Consortium (ECOG) Physical strength scores: Groups A and C: 0, 1, or 2; Group B: Patients >=75 years old with ECOG score 0-2; Patients >=18 years old and =75 years or age >=18 years and age =30ml/min and 1.5×ULN, but = 45ml/min* (if =45%*; *For patients aged= 30ml/min, or left ventricular ejection fraction5×ULN during the screening period, relevant tests (such as re-examination of coagulation function after a certain interval, deep vein ultrasound of lower extremity, etc.) were required to exclude deep vein thrombosis, blood hypercoagulability, and diffuse intravascular coagulation; 10.The researchers judged that the expected survival was more than 12 weeks; 11.Ability to perform treatment, visits, and study related tests as required by protocol; 12.Fertile female patients or their female partners fertile male patients must consent to the use of effective contraceptive methods, such as double barrier methods, condoms, oral or in
Exclusion criteria
Exclusion criteria: 1.Active central nervous system (CNS) leukemia; 2.A known history of clinically significant liver disease, including viral or other hepatitis or cirrhosis: Serologically positive hepatitis B surface antigen (HBsAg), requiring a negative hepatitis B virus (HBV) DNA test for admission; For patients who are serologically positive for antibodies to hepatitis C virus (HCV), a negative HCV RNA test is required to be enrolled; 3.Known human immunodeficiency virus (HIV) infection; 4.Pregnant (positive pregnancy test during screening) or breastfeeding women; 5.Meet any of the following heart-related criteria: Inherited long QT syndrome or QTcF>450 msec; A variety of clinically significant cardiovascular diseases, including acute acute myocardial infarction, unstable angina pectoris, coronary artery bypass surgery, and congestive heart failure classified by the New York College of Cardiology (NYHA) as grade 2 or higher within the first 6 months of enrollment; 6.The patient has had other malignancies in the past 5 years, except basal cell carcinoma of the skin after radical treatment, carcinoma in situ of the breast or carcinoma in situ of the cervix; 7.Prior anti-leukemia therapy (for patients in groups A and B), except for the following: control of white blood cell count with hydroxyurea or leukopexy, or all-trans retinoic acid therapy due to initial suspicion of acute promyelocytic leukemia, or non-demethylated drugs for MDS; 8.For patients in group C, previous anti-leukemia therapy, including chemotherapy, radiotherapy, hormone therapy, targeted therapy, or immunotherapy, was less than 2 weeks or 5 half-lives (whichever is shorter) prior to the start of study therapy; Have received autologous hematopoietic stem cell transplantation or CAR-T therapy within 60 days prior to the start of study therapy, or have not recovered from ASCT or CAR-T treatment-related toxicity; Patients who had undergone allogeneic hematopoietic stem cell transplantation within 100 days prior to the start of study therapy, or who still had active acute and chronic graft-versus-host disease, or who still required immunosuppressive therapy were excluded; 9.Previous treatment with targeted menin (for group A and Group B patients); 10.Existing non-hematological toxicity has not returned to grade 0 or 1 (except hair loss); 11.Patients who had chest CT examination within 1 month prior to screening and indicated pulmonary nodules should undergo T-spot examination (T cell SPOT test for tuberculosis infection) during the screening period, and those who found positive should be excluded (no additional examination is required for those who did not have chest CT examination within 1 month prior to screening). 12.Active infection that has not been controlled: Patients with non-severe infectious complications (such as oral candida infection or uncomplicated urinary tract infection) that are being treated with oral/topical anti-infective therapy can be enrolled; Severely infected patients requiring hospitalization or intravenous antibiotic treatment within the first 14 days of enrollment who have no evidence of infection and who are receiving prophylative antiinfective, antifungal, or antiviral therapy due to prolonged neutropenia may be enrolled; Patients who were treated with intravenous antibiotics or hospitalized for febrile neutropenia, but no evidence of infectious etiology was found, and whose body temperature was normal for more than 72 hours without the use of antipyretics cou
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of DLT and SAE;CRc; | — |
Secondary
| Measure | Time frame |
|---|---|
| Other types of AE incidence, abnormal laboratory tests, changes in vital signs, ECG changes, etc;PK endpoint: Blood drug concentration and various PK parameters of BN104 and its main metabolite M1 at a specific time point;ORR;OS;DOR; | — |
Countries
China
Contacts
Public ContactSuning Chen
The First Affiliated Hospital of Soochow University
Outcome results
None listed