Patients with relapsed/refractory acute myeloid leukemia (R/R AML) with IDH1 mutations Patients with relapsed/refractory acute myeloid leukemia (R/R AML) with IDH2 mutations
Conditions
Interventions
Queue 1(Control group):Intensive chemotherapy MEC regimen
Queue 1(Control group):Intensive chemotherapy FLAG±IDA regimen
Queue 1(Control group):LoDAC regimen
Queue 1(Control group):Azacitidine for Injection
Queue 1(Experimental group):HMPL-306 tablets
Queue 2(Experimental group):HMPL-306 tablets
Queue 2(Control group):Intensive chemotherapy MEC regimen
Queue 2(Control group):Intensive chemotherapy FLAG±IDA regimen
Queue 2(Control group):LoDAC regimen
Queue 2(Control group):Azacitidine for Injection
Sponsors
Peking University People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Have signed the ICF; 2.Be able to follow the requirements of the protocol; 3.Aged >= 18 years; 4.Eastern Cooperative Oncology Group (ECOG) Performance Status score: 0 or 2; 5.Cohort 1: Patients with R/R AML harboring IDH1-R132 site mutations (WHO 2022 Classification of Myeloid Neoplasms and Acute Leukemias);Cohort 2: Patients with R/R AML harboring IDH2-R140/R172 mutations (WHO 2022 Classification of Myeloid Neoplasms and Acute Leukemias). A patient with both IDH1 and IDH2 mutations is recommended to be included in Cohort 2 (IDH2 mutation group). 6.Agree to undergo bone marrow aspiration and/or biopsy before and during treatment; 7.Be willing to complete QoL assessments at specified time points during study treatment and after treatment discontinuation; 8.Female patients of childbearing potential must agree to use highly effective contraceptive methods during the study and within 30 days after discontinuation of the investigational product (the time limit of contraception for the chemotherapy group needs to be extended to 6 months after the last dose), as detailed in Appendix 9 (contraceptive requirements), and agree not to donate eggs (oocytes) for reproductive purposes during this period; patients must not be lactating and must have a negative pregnancy test (if of childbearing potential); 9.Male patients with female partners of childbearing potential must use condoms during intercourse and avoid donating or freezing sperm during the study and within 30 days after discontinuation of the investigational product (the time limit of contraception for the chemotherapy group needs to be extended to 6 months after the last dose).
Exclusion criteria
Exclusion criteria: 1.Patients who received prior treatment with an IDH1 inhibitor, IDH2 inhibitor, or IDH1/IDH2 dual-target inhibitor; 2.Patients with known RAS or FLT3 hotspot mutations; 3.Inadequate organ function, as defined below: •Serum total bilirubin (TBIL) higher than 1.5 times the upper limit of normal (ULN), excluding the following patients: -Patients with Gilbert's disease, with normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and serum TBIL = 3 × ULN. •AST or ALT > 2.5 × ULN (if leukemia invades the liver, patients with AST and ALT levels = 5 × ULN can be enrolled); •Glomerular filtration rate or creatinine clearance estimated using Cockcroft-Gault formula 1.5 × ULN or activated partial thromboplastin time (aPTT) > 1.5 × ULN, except for patients who are receiving anticoagulant therapy; 5.Blood amylase or blood lipase > 1.5 × ULN and assessed to be clinically significant by the investigator; 6.Current known history of liver disease, including cirrhosis, alcoholic liver disease, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV): •Chronic hepatitis B is defined as positive serum hepatitis B surface antigen (HBsAg). Patients with occult or previous HBV infection [defined as positive hepatitis B core antibody (HBcAb) and negative HBsAg] but negative HBV DNA test can be enrolled; such patients need to be tested for HBV DNA monthly; •Patients with positive HCV serology may be enrolled only if they test negative for HCV RNA; 7.Known human immunodeficiency virus (HIV) infection; 8.Meet any of the following cardiac function-related criteria: •Any clinically significant cardiac rhythm or conduction abnormality requiring clinical intervention; •Clinically significant cardiovascular diseases that require clinical intervention as judged by the investigator, including but not limited to: acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting within 6 months prior to enrollment, New York Heart Association (NYHA) Class II (inclusive) or above congestive heart failure, left ventricular ejection fraction (LVEF) 160 mmHg or diastolic blood pressure > 100 mmHg); •Congenital long QT syndrome or QTcF > 470 msec in females/QTcF > 450 msec in males; Note: QTcF = QT/?RR •Current use of medicines known to cause QT prolongation or Torsades de Pointes (See full list at http://www.crediblemeds.org); 9.Patients with other primary malignancies within the last 5 years, except for patients who have been cured and patients with the following non-invasive tumors that have been treated with definitive therapy: •Basal cell carcinoma of skin •Cutaneous cervical squamous cell carcinoma •Carcinoma in situ of cervix •Breast cancer in situ; 10.Pregnant (positive pregnancy test prior to treatment) or lactating women; 11.Males with childbearing requirements; 12.History of stroke or intracranial hemorrhage within 6 months prior to the first dose of investigational product; 13.Patients who have undergone major surgery within 4 weeks prior to the first dose of investigational product; 14.Patients who have received any monoclonal antibody for anti-tumor therapy within 4 weeks or 2 half-lives prior to the first dose of investigational product, whichever is longer; 15.Patients who have received treatment with the investigational product or investigational device in a clinical study wi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival (OS); | — |
Secondary
| Measure | Time frame |
|---|---|
| EFS;Safety assessment;CR rate;CR + CRh rate;CR + CRh + CRi rate;DoCR;Do(CR+CRh);Do(CR+CRi+CRh);TTCR;TT(CR+CRh);TT(CR+CRi+CRh); | — |
Countries
China
Contacts
Public ContactXiaojun Huang
Peking University People's Hospital
Outcome results
None listed