Gecacitinib in the Treatment of Steroid-Refractory/Dependent Chronic Graf Versus Host Disease (cGVHD).

A Single-Arm, Open-Label, Single-Center Phase Ib/IIa Clinical Study of Gecacitinib in the Treatment of Steroid-Refractory/Dependent Active Chronic Graf Versus Host Disease (cGVHD).

This study aims to evaluate the safety and efficacy of Gecacitinib in patients with steroid-refractory/dependent active chronic graft versus host disease (cGVHD).

Inclusion Criteria:

1. Age ≥ 18 years, regardless of gender.

2. Underlying hematologic malignancies or non-malignant disorders having received allogeneic hematopoietic stem cell transplantation.

3. Diagnosis of active cGVHD according to the 2014 NIH consensus criteria, meeting the definition of steroid-refractory or steroid-dependent cGVHD. Prior lines of cGVHD therapy are not restricted. Definitions are as follows:

   1. Steroid-refractory cGVHD is defined as meeting any of the following criteria: disease progression despite the use of prednisone ≥1 mg/kg/day (or equivalent dose of corticosteroids) for at least 1 week; OR, persistent disease symptoms with no improvement despite the use of prednisone ≥0.5 mg/kg/day or ≥1 mg/kg every other day (or equivalent dose of corticosteroids) for at least 4 weeks.
   2. Steroid-dependent cGVHD is defined as the requirement for a maintenance dose of prednisone >0.25 mg/kg/day or >0.5 mg/kg every other day (or equivalent dose of corticosteroids) to prevent disease flare or progression, and failure to successfully taper the dose to a lower level in at least 2 separate attempts spaced ≥8 weeks apart.

4. Platelet count ≥50 × 10⁹/L and absolute neutrophil count (ANC) ≥0.5 × 10⁹/L, without the use of colony-stimulating factors, androgens, erythropoietin, thrombopoietin, or platelet transfusion within 7 days prior to screening.

5. Adequate major organ function, defined as meeting the following criteria: ALT and AST ≤ 2.5 × upper limit of normal (ULN); direct and total bilirubin ≤ 2.0 × ULN; serum creatinine ≤ 1.5 × ULN.

6. Stable underlying disease without evidence of progression or relapse.

7. Karnofsky Performance Status (KPS) ≥ 60%.

8. Voluntarily participate in this study, provide signed informed consent, demonstrate good compliance, and be able to adhere to the study and follow-up procedures

Exclusion Criteria:

1. Post-transplant lymphoproliferative disorder, or loss of full donor chimerism due to other reasons.

2. Previous use of, or current treatment with, other JAK inhibitors at the time of screening.

3. History or presence of major diseases or clinically significant organ dysfunction that cannot be adequately controlled by treatment and may interfere with study completion:

   1. Congestive heart failure of New York Heart Association (NYHA) class III-IV, or documented history of diastolic or systolic dysfunction (e.g., left ventricular ejection fraction <40% by echocardiography), or uncontrolled/unstable angina or myocardial infarction.
   2. Uncontrolled diabetes (blood glucose >250 mg/dL or >13.9 mmol/L).
   3. Hypertension that cannot be adequately controlled to systolic blood pressure <160 mmHg and diastolic blood pressure <100 mmHg despite combination antihypertensive therapy.
   4. Peripheral neuropathy (Grade 2 or higher per NCI-CTCAE v5.0 criteria).

4. Patients with any uncontrolled bacterial, viral, or fungal infection.

5. Positive for HIV at screening, or active hepatitis B virus infection (HBsAg positive and HBV-DNA positive or above the upper limit of normal), or positive for HCV antibody with detectable HCV-RNA.

6. History of tuberculosis or positive interferon-γ release assay at screening.

7. Concurrent use of strong CYP3A4 inhibitors.

8. History of progressive multifocal leukoencephalopathy.

9. Known or suspected hypersensitivity to Gecacitinib hydrochloride, drugs of the same class, or any of their excipients.

10. Pregnant or lactating women, or patients unwilling to use effective contraception during Gecacitinib treatment and for 1 week after the last dose.

11. Inability to swallow oral tablets.