Clinical Trial of WBC100 Capsule in Relapsed/Refractory Acute Myeloid Leukemia

An Open-Label, Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic, and Preliminary Efficacy of WBC100 Capsules in Patients With Relapsed or Refractory Acute Myeloid Leukemia

The goal of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of WBC100 capsules in patients with relapsed or refractory acute myeloid leukemia (R/R AML). The main questions it aims to answer are:

• What is the safety and tolerability profile of WBC100 in R/R AML patients?
• Can WBC100 effectively induce remission in R/R AML patients?

Participants will:

• Take WBC100 capsules orally once daily in 28-day treatment cycles;
• Undergo regular safety assessments, including adverse event monitoring and laboratory tests;
• Provide blood samples for pharmacokinetic (PK) analysis;
• Have their remission status and efficacy evaluated according to the ELN2022 criteria.

Inclusion Criteria:

• 1. Signed informed consent and compliance with study procedures;

• 2. Male or female participants aged ≥18 years at the time of consent;

• 3. Diagnosis of relapsed or refractory acute myeloid leukemia (R/R AML) according to the 2016 World Health Organization (WHO) classification;

• 4. ECOG PS 0-2;

• 5. Life expectancy ≥3 months;

• 6. Adequate bone marrow reserve and organ function as defined below:

  1. Bone marrow reserve: Peripheral WBC < 25 × 10⁹/L (leukocyte-reducing agents are allowed, with a washout period of at least 5 half-lives prior to study drug administration);
  2. Coagulation: International normalized ratio (INR) ≤ 2;
  3. Hepatic function: Total bilirubin (TBIL) ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN. In cases of hepatic involvement: ALT or AST ≤ 5 × ULN, and TBIL ≤ 3 × ULN;
  4. Renal function: Creatinine clearance ≥60 mL/min (Cockcroft-Gault), or serum creatinine ≤1.5 × ULN;
  5. Cardiac function: Left ventricular ejection fraction (LVEF) ≥50%; QTcF ≤450 ms for males, ≤470 ms for females.

• 7. Female participants of childbearing potential and fertile male participants with partners of childbearing potential must use medically approved contraception during treatment and for 6 months after the final dose.

Exclusion Criteria:

• 1. Known hypersensitivity to WBC100 capsules or any of their excipients;

• 2. Diagnosis of acute promyelocytic leukemia (APL);

• 3. Diagnosis of mixed phenotype acute leukemia, chronic myeloid leukemia in blast crisis, or AML transformed from myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN);

• 4. Subjects with relapse after allogeneic HSCT, grade ≥ 2 acute GVHD, extensive chronic GVHD requiring immunosuppressive therapy, or autologous HSCT within the past 90 days;

• 5. Subjects who have undergone major surgery, have active ulcers, or have unhealed wounds within 28 days prior to the first dose;

• 6. Received other investigational drugs or treatments within 28 days prior to the first administration, or are still within the safety follow-up period of another clinical trial;

• 7. Subjects with a history of severe cardiovascular or cerebrovascular conditions, including but not limited to:

  1. Significant arrhythmias or conduction disorders (e.g., ventricular arrhythmias, Grade II-III AV block);
  2. Thromboembolic events requiring anticoagulation or presence of vena cava filter;
  3. NYHA Class III-IV heart failure;
  4. Poorly controlled hypertension (SBP ≥140 mmHg or DBP ≥90 mmHg despite treatment).

• 8. Evidence of severe or uncontrolled systemic diseases, such as refractory effusions, poorly controlled diabetes, or significant disorders of the psychiatric, neurological, cardiovascular, respiratory, endocrine, gastrointestinal, hepatic, or renal systems;

• 9. History or presence of immunodeficiency, autoimmune disease requiring systemic immunosuppressants, or organ transplantation;

• 10. Congestive heart failure, aortic dissection, stroke (excluding lacunar infarct), unstable angina, myocardial infarction, bypass surgery, or pulmonary embolism within 180 days prior to first dosing;

• 11. Known risk factors for QT prolongation, including congenital long QT syndrome or drug-induced arrhythmia history;

• 12. Positive for syphilis antibodies, HIV, active HBV infection (HBsAg+ or HBcAb+ with HBV DNA ≥1000 IU/mL), or active HCV infection (HCV Ab+ with detectable HCV RNA);

• 13. Active infection requiring systemic treatment, including uncontrolled bacterial, viral, or fungal infections;

• 14. Gastrointestinal conditions preventing oral drug intake or absorption, such as severe vomiting, chronic diarrhea, intestinal stoma, malabsorption, or inability to swallow;

• 15. Use of strong CYP450 inhibitors/inducers that cannot be stopped ≥7 days before dosing;

• 16. Receipt of monoclonal antibodies, ADCs, radiotherapy within 28 days (14 days for localized radiotherapy), cytotoxic chemotherapy, targeted small molecules within 14 days or 5 half-lives, or CAR-T therapy within 100 days;

• 17. Receipt of any live or attenuated vaccines (e.g., influenza, varicella) within 28 days;

• 18. History of other malignancies within 2 years, except adequately treated basal cell carcinoma, carcinoma in situ of cervix or breast, or squamous cell carcinoma of the skin;

• 19. History of psychiatric or neurological disorders that may interfere with protocol compliance;

• 20. Inability to tolerate venous blood draws;

• 21. Pregnant or breastfeeding women, or women with positive serum hCG during screening;

• 22. Any condition deemed by the investigator to make the subject unsuitable for study participation.