Relapsed/Refractory Acute Leukemia with NPM1 Mutation or KMT2A Rearrangement
Conditions
Interventions
Trial group:Subjects will receive oral BY002 at a starting dose of 50 mg twice daily (BID), with each cycle consisting of 28 days. The dose will be sequentially escalated to 100 mg BID (100% increase)
Sponsors
The First Affiliated Hospital of Soochow University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Patients with relapsed/refractory acute leukemia diagnosed according to the 2022 World Health Organization (WHO) criteria, including AML, ALL and mixed phenotype acute leukemia, excluding acute promyelocytic leukemia; 2. Subjects confirmed to be complicated with NPM1 gene mutation or KMT2A rearrangement. 3. Aged >= 18 years; 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2; 5. Adequate hepatic, renal and cardiac function; 6. Estimated survival of more than 6 months as assessed by the investigator; 7. Be able to receive treatment, complete study visits and undergo research-related examinations in accordance with the protocol requirements. 8. Females of childbearing potential, and male subjects with female partners of childbearing potential, must agree to use effective contraceptive measures throughout the study period and for 30 days after the last study drug administration. Valid contraception methods include double-barrier contraception, condoms, oral or injectable contraceptives, and intrauterine devices. Postmenopausal women (over 45 years of age with amenorrhea for more than 1 year) and surgically sterilized women are exempt from this requirement.
Exclusion criteria
Exclusion criteria: 1. With confirmed active central nervous system leukemia; 2. Known history of clinically significant liver disease, including viral or other forms of hepatitis or liver cirrhosis; 3. Known human immunodeficiency virus (HIV) infection; 4. Pregnant women (with a positive pregnancy test at screening) or breastfeeding women; 5. Meet any of the following cardiac-related criteria: Congenital long QT syndrome or QTcF > 450 msec; Any clinically significant cardiovascular diseases, including acute myocardial infarction, unstable angina, coronary artery bypass grafting within 6 months prior to enrollment, and congestive heart failure with New York Heart Association (NYHA) functional class >>= Grade 2. 6. Patients with other malignant tumors within the past 5 years, excluding basal cell carcinoma of the skin, breast carcinoma in situ, cervical carcinoma in situ and other malignancies that have received curative treatment. 7. Have received autologous hematopoietic stem cell transplantation (ASCT) or chimeric antigen receptor T-cell (CAR-T) therapy within 60 days prior to screening, or have unresolved toxicities associated with ASCT or CAR-T treatment; 8. Have undergone allogeneic hematopoietic stem cell transplantation within 100 days prior to screening, or still present with active acute or chronic graft-versus-host disease, or still require immunosuppressive therapy; 9. Have received anti-leukemia therapy within 2 weeks prior to study initiation, including chemotherapy, radiotherapy, hormone therapy or immunotherapy (excluding hydroxyurea); 10. Previous participation in other clinical trials of investigational drugs, with an interval of less than 2 weeks or 5 half-lives (whichever is shorter) after the last administration of small-molecule drugs, or less than 4 weeks or 5 half-lives (whichever is shorter) after the last administration of macromolecular drugs (e.g., antibody drugs). 11. Toxic reactions from prior anti-leukemia treatment have not recovered to Grade 0 or 1 level (alopecia excluded); 12. Uncontrolled active infection; 13. Subjects with known dysphagia, intestinal syndrome, gastroparesis, or other conditions that limit oral drug intake or gastrointestinal absorption; 14. Those with a history of severe allergy to Menin inhibitors or hypersensitivity to any component of BY002; 15. Insufficient patient compliance with participation in this clinical study as judged by the investigator; 16. Any other diseases, metabolic abnormalities, abnormal physical examination findings, or clinically significant abnormal laboratory results, which, in the investigator’s judgment, may render the patient unsuitable for receiving the study drug, interfere with the interpretation of study results, or place the patient at excessive clinical risk; 17. The expected survival time of subjects is no more than 6 months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Limiting Toxicity;To determine the MTD and/or RP2D of BY002 in the treatment of patients with relapsed/refractory acute leukemia; | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate the PK profiles of BY002 in patients with relapsed/refractory acute leukemia.;Preliminarily evaluate the preliminary efficacy of BY002 in the treatment of patients with relapsed/refractory acute leukemia; | — |
Countries
China
Contacts
Public ContactSuning Chen
The First Affiliated Hospital of Soochow University
Outcome results
None listed