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

Official title

A Study on the Safety and Efficacy of Gecacitinib in Patients With Chronic Graft-versus-Host Disease (cGVHD) Who Have Received Prior Treatment With Two or More Systemic Therapies

Overview

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.

Interventions

• Drug Gecacitinib Hydrochloride Tablets
  Gecacitinib hydrochloride tablets are taken orally on an empty stomach. The starting dose is 50 mg once daily (QD). The maximum dose is 100 mg twice daily (BID), and the minimum dose is 50 mg every other day (QOD). Dose adjustments should be made in 50-mg increments or decrements.

Primary outcome measures

• Overall Response Rate (ORR) at Week 24 [Time frame: Week 24]

Secondary outcome measures (11)

• ORR at Week 12, 48 and 60 [Time frame: week 12, 48 and 60]
• Failure-free Survival (FFS) [Time frame: Up to 24 months]
• Change From Baseline in Lee cGVHD Symptom Scale Scores [Time frame: Through study completion, an average of 24 months]
• Best Overall Response (BOR) [Time frame: Up to week 24]
• Duration of Response (DOR) [Time frame: Up to 24 months]
• Percentage of Participants With a ≥50% Reduction in Daily Corticosteroid Dose for ≥4 Weeks [Time frame: Up to Day 180]
• Relapse Rate [Time frame: Up to 24 months]
• Overall Survival (OS) [Time frame: Up to 24 months]
• Change from Baseline in FACT-BMT [Time frame: Through study completion, an average of 24 months]
• Change from Baseline in EQ-5D-5L [Time frame: Through study completion, an average of 24 months]
• Adverse Events (AEs) and Adverse Drug Reactions (ADRs) [Time frame: Up to 28 days after the last dose]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University First Hospital — Beijing

Identifiers

NCT: NCT07012304 · cGVHD-06

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗