Overview

The purpose of this clinical trial is to evaluate the safety of TQB3454 tablets in patients with acute myeloid leukemia and myelodysplastic syndrome, and determine the phase II recommended dose.

Eligibility

Inclusion Criteria:

• Patients voluntarily joined the study and signed informed consent with good compliance.
• Men and women; The expected survival is ≥3 months.
• Negative serum/urine pregnancy test within 7 days prior to initial dose and must be non-lactating; Women of childbearing age agree to use contraception (such as an intrauterine device, birth control pill or condom) during the study and for six months after the study completion; Men agreed to use contraception during the study period and for six months after the end of the study.
• The major organs are functioning well;
• For Relapsing/refractory acute myeloid leukemia (AML):
  1. According to the classification criteria for Hematopoietic and lymphoid tissue tumors revised by the World Health Organization (WHO) in 2016, AML confirmed by bone marrow cell morphology, excluding acute promyelocytic leukemia (APL).
  2. ≥18 years old; Eastern Cooperative Oncology Group (ECOG) score is 0~2.
  3. Blood biochemical examination:
  4. Total bilirubin (TBIL) ≤1.5× upper limit of normal value (ULN), liver infiltration ≤3×ULN in Gilbert syndrome patients or tumor diseases; ii: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; ALT and AST≤5×ULN if liver infiltration was associated.
• For myelodysplastic syndrome (MDS) with higher risk:
  1. MDS patients were confirmed by bone marrow cell morphology and cytogenetics and met the classification criteria of hematopoietic and lymphoid tissue tumors revised by WHO in 2016.
  2. ≥18 years old; ECOG score is 0~2. c. Blood biochemical examination:
  3. Total bilirubin (TBIL) ≤1.5× upper limit of normal value (ULN), liver infiltration ≤3×ULN in Gilbert syndrome patients or tumor diseases.

        ii: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; ALT and
        AST≤5×ULN if concomitant with liver infiltration.
        Exclusion Criteria:
          -  Tumor diseases and history:
               1. The tumor has or is suspected to involve the central nervous system, or primary
                  Central nervous system leukemia.
               2. Present or present with other malignant tumors within 3 years prior to the first
                  dose. Except the following conditions: for other malignancies treated with a
                  single operation, achieving a 5-year continuous disease-free survival (DFS);
                  Cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial
                  bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor
                  infiltrating basal membrane)].
               3. Severe life-threatening complications of leukemia, such as uncontrolled bleeding,
                  hypoxia or shock pneumonia, and disseminated intravascular coagulation.
          -  Previous antitumor therapy:
               1. Received National Medical Products Administration (NMPA) approved Chinese patent
                  drugs with anticancer indications specified in the drug label within 2 weeks
                  prior to initial administration.
               2. Toxicities associated with previous antineoplastic therapy did not return to
                  CTCAE≤1, except for hair loss, fatigue and poor appetite.
                  3. Associated diseases and history:
               1. Abnormal liver.
               2. Renal abnormalities.
               3. Gastrointestinal abnormalities.
               4. Cardio-cerebrovascular abnormalities.
               5. Immune-related history.
               6. Lung disease.
               7. Comorbidities that were severe or poorly controlled and, in the investigator's
                  judgment, significantly compromised patient safety or hindered study completion.
               8. Risk of bleeding.
          -  History of drug abuse or drug abuse.
          -  Participated in clinical trials of other drugs within the past 30 days;
          -  It is estimated that the patient's compliance to participate in this clinical study is
             insufficient.