Relapsed/refractory acute myeloid leukemia
Conditions
Interventions
experimental group:Seven dosing groups are planned, namely 20 mg, 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, and 140 mg groups, administered once daily (qd). The first two dosing groups adopt "accelerated t
Sponsors
The First Affiliated Hospital, Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Age 18~70 years old, male or female; 2. In line with the World Health Organization (WHO) 2016 version of the AML diagnostic criteria, not suitable for patients with relapsed/refractory acute myeloid leukemia after existing treatment or >=2 lines of treatment. Definition of relapsed/refractory acute myeloid leukemia (according to the 2017 edition of the Chinese Guidelines for Diagnosis and Treatment): (1) Diagnostic criteria for relapsed AML: leukemia cells reappeared in peripheral blood after complete remission (CR) or blast cells in bone marrow >5% (except for consolidation chemotherapy) after bone marrow regeneration and other reasons) or extramedullary infiltration of leukemia cells. (2) Diagnostic criteria for refractory AML: naive patients who were ineffective after 2 courses of standard regimens; patients who relapsed within 12 months after consolidation and intensive therapy after CR; patients who relapsed after 12 months but were ineffective after conventional chemotherapy; Repeated relapse; persistent extramedullary leukemia. 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; 4. Expected survival period >= 3 months; 5. The level of organ function is basically normal: (1) Total bilirubin (TBIL) =60 ml/min (calculated according to Cockcroft Gault formula); (3) Activated partial prothrombin time (APTT) =50%; Fridericia-corrected QT interval (QTcF) <450 ms for males and <470 ms for females; 6. Those who can complete the research procedures and follow-up inspections according to the research protocol; 7. Patients who are able to understand and voluntarily sign a written informed consent form that must be signed prior to performing the study procedures specified in any trial.
Exclusion criteria
Exclusion criteria: 1. Patients diagnosed with acute promyelocytic leukemia (the French-American-British collaboration group classification AML-M3 or the 2016 WHO diagnostic classification of acute promyelocytic leukemia with PML-RARa); 2. In addition to AML, other malignant tumors (and the malignant tumor is active), AML patients secondary to other tumors (including myelodysplastic syndrome, breast cancer, etc.); 3. White blood cells (WBC) > 25×10^9/L at screening (allow to take hydroxyurea until 3 days before administration of the test drug to stabilize the WBC count); 4. Men, women of childbearing age (postmenopausal women must have been in menopause for at least 12 months to be considered infertile) and their partners are reluctant to take the investigator during treatment and for at least 3 months after the last dose of study drug Contraceptive measures deemed effective, as well as for pregnant and breastfeeding women; 5. Patients who received radiation therapy, immunotherapy, hormone therapy, targeted therapy, biological therapy, traditional Chinese medicine therapy, chemotherapy or any clinical research treatment within 14 days before receiving the study drug for the first time; 6. Patients who have received hematopoietic stem cell transplantation; 7. Patients with persistent toxicity that has not recovered to CTCAE version 5.0 below grade 2 due to previous chemotherapy drugs or radiation therapy (except for alopecia); 8. Major surgery or significant traumatic injury within 28 days before first receiving the investigational drug, or is expected to require major surgery during the study treatment; 9. According to the judgment of the investigator, patients with dysphagia or any gastrointestinal disease that affects drug absorption; 10. Patients who have taken strong inhibitors or inducers of CYP3A liver metabolic enzymes within 14 days before receiving the test drug for the first time; 11. Persons with active fungal, bacterial, and/or viral infections with symptoms; 12. Known HIV infection (anti-HIV positive), active hepatitis B (HBsAg positive test and HBV DNA >= 2000 copies/mL or >= 500 IU/mL), or active hepatitis C (HCV antibody test positive and HCV RNA Positive PCR test results, or syphilis infection (positive Treponema pallidum antibody test); patients with inactive hepatitis B or C who require long-term oral antiviral drugs during the trial need to be excluded; 13. Any poorly controlled clinical problems (such as severe mental, neurological, cardiovascular, respiratory, digestive, urinary, coagulation and other systemic diseases); 14. Any other circumstances or conditions for which the researcher believes that the patient is not suitable to participate in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK parameter;Objective Response Rate, ORR;Time-to-response, TTR;Duration of Overall Response, DOR; | — |
Countries
China
Contacts
Public ContactJie Jin
The First Affiliated Hospital, Zhejiang University School of Medicine
Outcome results
None listed