Efficacy and Safety of Gecacitinib Hydrochloride in Prophylaxis Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Myelofibrosis

Exclusion Criteria

• •Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy.
• •Hepatic insufficiency defined as bilirubin ≥ 2 × upper limit of normal (ULN), except for patients with a history of Gilbert Syndrome.
• •Renal impairment defined as serum creatinine \> 2 mg/dL.
• •Cardiac dysfunction defined as left ventricular ejection fraction (LVEF) ≤ 45%.
• •Pulmonary dysfunction defined as forced expiratory volume in the first second (FEV1) or diffusing capacity for carbon monoxide (DLCO) (corrected for hemoglobin) ≤ 50% of predicted value.
• •Chronic or active infection requiring systemic therapy during the peri-transplant and post-transplant period.
• •Diagnosis of another active malignancy within the past 12 months, except for adequately treated non-melanoma skin cancer, adequately treated melanoma of grade 2 or below, or cervical intraepithelial neoplasia. Active malignancy is defined as malignancy undergoing active treatment.
• •Any significant clinical or laboratory abnormality that may compromise safety evaluation, such as:
• •1. Uncontrolled diabetes mellitus (fasting blood glucose \> 13.9 mmol/L);
• •2. Hypertension uncontrolled by two or more antihypertensive agents (systolic blood pressure ≥ 160 mmHg, diastolic blood pressure ≥ 100 mmHg);
• •3. Peripheral neuropathy of grade ≥ 2 per NCI-CTCAE v5.0.
• •Pre-transplant diagnosis of gastrointestinal impairment or disease that may affect drug absorption, including ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or history of gastrectomy or intestinal resection.
• •Cholestatic disease or sinusoidal obstruction syndrome / hepatic veno-occlusive disease at screening (defined as persistent bilirubin abnormality and progressive organ dysfunction not due to graft-versus-host disease).
• •Active and uncontrolled viral infection at screening, including CMV, EBV, HIV (positive anti-HIV antibody), HBV (positive HBsAg or positive HBV-DNA), HCV (positive anti-HCV antibody or positive HCV-RNA).
• •Active tuberculosis within 6 months prior to screening.
• •History of epilepsy or use of psychotropic or sedative medications at screening.
• •Female patients who are pregnant, breastfeeding, or planning pregnancy, or who cannot use effective contraception throughout the study; male patients who do not use condoms during dosing and for 2 days (approximately 5 half-lives) after the last dose.
• •History of malignancy other than the transplanted tumor within the previous 5 years.
• •Use of anticoagulant or antiplatelet agents (except low-molecular-weight heparin).
• •Presence of other severe diseases that, in the investigator's opinion, may affect patient safety or compliance.
• •Suspected hypersensitivity to geltrectinib hydrochloride, its analogs, or any of its excipients.
• •Participation in another clinical trial of an investigational drug or medical device within 4 weeks prior to screening.
• •Any other condition that, in the investigator's judgment, renders the patient ineligible for the study.