R/R Acute Myeloid Leukemia (AML)
Conditions
Interventions
Single arm:HE006 tablet
Sponsors
Institute of Hematology, Blood Disease Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria: 1.Participant must understand and voluntarily sign an Informed Consent Form (ICF) prior to any study-related assessments/procedures being conducted. 2. 18 years and older, regardless of gender; 3. Relapsed/refractory acute myeloid leukemia (except acute promyelocytic leukemia) diagnosed according to the World Health Organization (WHO) Classification of Myeloid Neoplasms and Acute Leukemia (2016) and without standard treatment scheme, intolerable to standard treatment or unable to carry out standard treatment; According to the Diagnosis and Treatment Guidelines for Relapsed and Refractory Acute Myeloid Leukemia in China (2021 Edition), the definition of relapse/refractory is as follows: Recurrent acute myeloid leukemia: leukemia cells reappear in the peripheral blood or primitive cells in the bone marrow = 5% after CR (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or leukemic cell infiltration occurs outside the marrow (in the dose increasing stage, for patients with the first relapse, the duration of remission needs to be = 12 months); Refractory acute myeloid leukemia: the first treatment cases that failed to respond to 2 courses of treatment with the standard scheme; Those who recurred within 12 months after CR after consolidation and intensive treatment; Those who recur after 12 months but fail to respond to conventional chemotherapy; 2 or more relapses; Persistent extramedullary leukemia 4. Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; 5. Participant must have a projected life expectancy of at least 3 months; 6. Participants must have basically normal functions of the main organs , and the laboratory test values in the screening period met the following standards: Hematology: white blood cell count = 30 × 109/L Kidney: serum creatinine < 1.5 × ULN Or calculate creatinine clearance rate (Ccr) (Cockcroft Gault formula [see Appendix 12.3]) (serum creatinine = 1.5 × ULN) = 60 mL/min Liver: TBIL (serum) < 1.5 × ULN (with Gilbert syndrome<3 × ULN) AST and ALT < 2.5 × ULN Coagulation: INR or prothrombin time (PT) < 1.5 × ULN 7. All acute toxic reactions of previous anti-tumor treatment or surgery were relieved to baseline or = 1 level (NCI-CTCAE Version 5.0) (except for the toxicity of alopecia, hematology and other researchers that considered no safety risk to patients); 8. The results of serum pregnancy test of female patients of childbearing age in screening period were negative. Female patients agree to use reliable contraceptive methods within 6 months from signing ICF to the last take medicine.Male patients agreed to use reliable contraceptive methods within 3 months from signing ICF to the last take medicine. Including but not limited to: abstinence, male undergoing vasectomy, female sterilization, effective intrauterine devices or condoms, and effective contraceptives. Note: Women of non childbearing age include permanent sterilization (hysterectomy, bilateral oophorectomy or bilateral salpingectomy) and menopause. For women = 50 years of age, if they ha
Exclusion criteria
Exclusion criteria: 1. Patients who suffered from unstable or serious concurrent diseases within 6 months before the first administration, which may hinder the whole process of the study according to the judgment of the investigator, such as pancreatitis, severe/unstable angina, symptomatic congestive heart failure, myocardial infarction and/or pulmonary hypertension, life-threatening ventricular arrhythmia under maintenance treatment, stroke and uncontrolled severe seizures 2. ECG examination in screening period showed that male QTcF>450 ms, female QTcF>470 ms (QTc interval must be corrected by Fridericia formula for heart rate); 3. Known acute or active hepatitis B/C, or syphilis infection, or human immunodeficiency virus (HIV) infection, including a) HBsAg positive or HBsAg negative, and HBcAb positive persons with positive copies of hepatitis B virus deoxyribonucleic acid (HBV DNA) at the same time (defined as exceeding the lower detection limit of the research center); b) Hepatitis C virus (HCV) antibody is positive and hepatitis C virus ribonucleic acid (HCV RNA) is positive. Allow patients to receive stable antiviral treatment; 4. There is systemic bacterial, viral, fungal or parasitic infection (except fungal nail infection) with poor activity control, or other clinically significant active infectious disease processes, and the investigator and sponsor consider that the patient is not suitable to participate in the clinical trial; 5. Have dysphagia or gastrointestinal diseases that affect drug absorption, and are in an acute attack (such as Crohn's disease, ulcerative colitis, or short bowel syndrome) or other malabsorption conditions; 6. Pulmonary interstitial diseases with clinical significance (such as pulmonary interstitial fibrosis, interstitial pneumonia); 7. Patients with active liver or biliary diseases (except Gilbert syndrome, asymptomatic gallstones or other chronic liver diseases assessed as stable by the investigator); 8. Patients who have undergone other therapeutic operations (including local treatment) other than diagnosis, biopsy and drainage within 4 weeks before the first administration, or who are expected to undergo major surgery during the study period. For patients who have undergone drainage (such as thoracic cavity, biliary tract, etc.) and/or placed drainage tubes within 4 weeks before the first administration, relevant symptoms/signs should have been basically alleviated without the need for preventive/therapeutic use of antibiotics; 9. Patients who have undergone major surgery (excluding puncture biopsy) or severe trauma within 4 weeks before the first medication; Or elective surgery is required during the study period; 10. Patients who received radiotherapy within 4 weeks before the first administration. Palliative radiotherapy (= 10 fractionated radiotherapy) shall be completed at least 48 hours before the first administrat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity(DLT);AE;Laboratory examination (including blood routine examination, blood biochemistry, urine routine examination, blood coagulation function), physical examination, weight, vital signs, American Eastern Cooperative Oncology Group (ECOG) score, 12 lead electrocardiogram (ECG). ;Maximum tolerated dose(MTD),Maximum Ascending dose(MAD)and Recommended phase II Dose(RP2D) ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic parameters for single and multiple administration;Objective remission rate(Including complete remission with negative minimal residual lesions [CRMRD -],Complete Remission(CR),Complete Remission with incomplete hematologic recovery(CRi),Morphological leukemia-free state(MLFS),Partial Remission(PR),Duration of Response(DOR),Event free survival(EFS),Relapse free survival,Overall Survival(RFS) ; | — |
Countries
China
Contacts
Public ContactWang Jiangxiang
Institute of Hematology, Blood Disease Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed