Gecacitinib for cGVHD: Safety and Efficacy in Patients After ≥2 Lines of Prior Therapy

Yujun DONG

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Chronic Graft Versus Host Disease

Treatments

Drug: Gecacitinib Hydrochloride Tablets

Study type

Interventional

Funder types

Other

Identifiers

NCT07012304

cGVHD-06

Details and patient eligibility

About

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.

Enrollment

24 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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