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

Korábbi kezelés

• Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy.
• Active tuberculosis within 6 months prior to screening.
• Participation in another clinical trial of an investigational drug or medical device within 4 weeks prior to screening.

Más betegség

• 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.
• 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.
• 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).
• History of epilepsy or use of psychotropic or sedative medications at screening.
• History of malignancy other than the transplanted tumor within the previous 5 years.
• 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.
• Any other condition that, in the investigator's judgment, renders the patient ineligible for the study.

Laborértékek

• 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.
• Any significant clinical or laboratory abnormality that may compromise safety evaluation, such as:
  • Uncontrolled diabetes mellitus (fasting blood glucose > 13.9 mmol/L);
  • Hypertension uncontrolled by two or more antihypertensive agents (systolic blood pressure ≥ 160 mmHg, diastolic blood pressure ≥ 100 mmHg);
  • Peripheral neuropathy of grade ≥ 2 per NCI-CTCAE v5.0.
• 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).

Egyéb

• 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.
• Use of anticoagulant or antiplatelet agents (except low-molecular-weight heparin).

• Voluntarily sign the informed consent form (ICF), and be aged ≥ 18 years at the time of signing.
• Diagnosis of primary myelofibrosis (PMF) according to the 2016 WHO criteria (DIPSS intermediate-2/high risk, MPISS70 high/very high risk, or RR6 high risk), or post-ET/PV secondary myelofibrosis (MYSEC intermediate-2/high risk), with intention to undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT).
• Recipient with myelofibrosis scheduled to receive myeloablative conditioning allo-HSCT from a matched unrelated donor, matched sibling donor, or haploidentical donor.
• Karnofsky Performance Scale score ≥ 60.
• Eastern Cooperative Oncology Group (ECOG) performance status score 0-2.
• Male participants must agree to abstinence or use barrier contraception throughout the study.
• Female participants of childbearing potential must have a negative pregnancy test and agree to use two effective methods of contraception throughout the study.
• Ability to swallow tablets.
• Ability to comply with study and follow-up procedures.