Chronic Graft-versus-Host Disease (cGVHD) is a common late complication following allogeneic hematopoietic stem cell transplantation and a leading non-relapse cause of death. It is often treatment-refractory, significantly affecting patients' quality of life and prognosis. This study will evaluate the feasibility, safety, and tolerability of gecacitinib, a novel JAK and ACVR1 inhibitor, in 24 patients with moderate-to-severe cGVHD who have undergone two or more prior therapies. Participants will receive gecacitinib hydrochloride tablets for at least 24 weeks. Patients demonstrating disease stability, as assessed by the investigator, may continue treatment with the study drug until week 60, unless intolerability, disease progression, or initiation of new systemic therapy, whichever occurs first.

Inclusion Criteria:

• Voluntarily Signed informed consent and aged ≥18 years
• Undergone nonmyeloablative, myeloablative, or reduced-intensity allo-HSCT using bone marrow, peripheral blood stem cells, or umbilical cord blood from any donor source
• Confirmed myeloid and platelet engraftment: ANC >1.0×10⁹/L and platelet count >25×10⁹/L; no hematopoietic growth factors or blood product transfusions within 7 days before screening
• Clinically diagnosed moderate-to-severe cGVHD according to the 2014 NIH
• Received 2-5 prior systemic cGVHD therapies with persistent disease
• ECOG PS score of 0-2
• Able to swallow tablets
• Concomitant use of non-interacting immunosuppressants permitted

Exclusion Criteria:

• Recurrence of malignancy or loss of full donor chimerism
• Concurrent use of other JAK inhibitors, mesenchymal stem cells, or belumosudil (Eligible if discontinued for >8 weeks post-aGVHD treatment or stopped JAK inhibitors for cGVHD due to side effects.)
• Severe pulmonary cGVHD (FEV1 ≤39% or NIH lung symptom score of 3)
• Post-transplant lymphoproliferative disease
• Significant abnormalities affecting safety assessment, such as uncontrolled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg) despite ≤2 antihypertensives; ALT/AST >3×ULN; DBIL/TBIL >1.5×ULN; serum creatinine >1.5×ULN
• History of major cardiovascular events within 6 months.
• Arrhythmia requiring treatment at screening
• Gastrointestinal conditions impairing drug absorption
• Surgery within 4 weeks of screening with incomplete recovery
• Active/uncontrolled infections (viral, bacterial, parasitic, fungal) requiring treatment
• Active tuberculosis within 6 months
• Epilepsy or use of psychotropic/sedative drugs
• Pregnant/breastfeeding or unwilling to use contraception during and 4 weeks post-study
• Malignancy within 5 years (except the indication for transplant)
• Use of anticoagulants/platelet inhibitors (except low-molecular-weight heparin)
• Herbal medicine use within 1 week prior to enrollment
• Hypersensitivity to gecacitinib or its components
• Participation in another clinical trial within 4 weeks (or 5 half-lives of the previous study drug, whichever is longer)
• Deemed unsuitable by the investigator