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

Official title

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).

Overview

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

Interventions

• Drug Gecacitinib
  Phase Ib: Four dose cohorts of Gecacitinib are planned: 50 mg qd, 50 mg bid, 150 mg/day, and 100 mg bid. Dose escalation or de-escalation will follow the standard "3+3" design, starting at 50 mg BID. The dose may be escalated to 150 mg/day or 100 mg BID, or de-escalated to 50 mg qd. Subjects will receive continuous dosing for 28 days, or until they experience Dose-Limiting Toxicities (DLTs), cGVHD progression, or initiate new systemic therapy (whichever occurs first). Subjects who do not experie

Primary outcome measures

• phase Ib: Maximal Tolerable Dose (MTD) [Time frame: Baseline up to 28 days]
• phase IIa: Overall response rate (ORR) on Cycle 7 Day 1 [Time frame: Cycle 7 Day 1]

Secondary outcome measures (12)

• phase Ib: Recommended phase II dose (RP2D) [Time frame: Baseline up to 28 days]
• phase IIa: Rate of Failure-free Survival (FFS) [Time frame: Baseline to when the last participant reached Cycle 7 Day 1]
• phase IIa: Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score [Time frame: Cycle 7 Day 1]
• phase IIa: Best overall response (BOR) [Time frame: Cycle 7 Day 1]
• phase IIa: Proportion of patients who achieved ORR (CR+PR) at Cycle 4 Day 1. [Time frame: Cycle 4 Day 1]
• phase IIa: Duration of Response (DOR) [Time frame: From first response until cGVHD progression, death, or the date of change/addition of systemic therapies for cGVHD, whichever comes first, assessed up to Cycle 7 Day 1.]
• phase IIa: Organ-Specific Response Rate [Time frame: Cycle 7 day 1]
• phase IIa: Proportion of patients with ≥50% reduction in daily steroid dose [Time frame: Cycle 7 Day1]
• phase IIa: Proportion of patients successfully tapered off all steroids [Time frame: Cycle 7 Day 1]
• phase IIa: Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) [Time frame: Baseline; up to Cycle 7 Day 1]
• phase IIa: Change From Baseline in EQ-5D-5L [Time frame: Baseline; up to Cycle 7 Day 1]
• phase IIa: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) [Time frame: From first dose to 28 days post last dose, up to Cycle 8 Day 1]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years, regardless of gender.
• Underlying hematologic malignancies or non-malignant disorders having received allogeneic hematopoietic stem cell transplantation.
• 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:

• 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.
• 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.
• 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.
• 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.
• Stable underlying disease without evidence of progression or relapse.
• Karnofsky Performance Status (KPS) ≥ 60%.
• 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

• Post-transplant lymphoproliferative disorder, or loss of full donor chimerism due to other reasons.
• Previous use of, or current treatment with, other JAK inhibitors at the time of screening.
• History or presence of major diseases or clinically significant organ dysfunction that cannot be adequately controlled by treatment and may interfere with study completion:

• 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.
• Uncontrolled diabetes (blood glucose >250 mg/dL or >13.9 mmol/L).
• Hypertension that cannot be adequately controlled to systolic blood pressure <160 mmHg and diastolic blood pressure <100 mmHg despite combination antihypertensive therapy.
• Peripheral neuropathy (Grade 2 or higher per NCI-CTCAE v5.0 criteria).
• Patients with any uncontrolled bacterial, viral, or fungal infection.
• 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.
• History of tuberculosis or positive interferon-γ release assay at screening.
• Concurrent use of strong CYP3A4 inhibitors.
• History of progressive multifocal leukoencephalopathy.
• Known or suspected hypersensitivity to Gecacitinib hydrochloride, drugs of the same class, or any of their excipients.
• Pregnant or lactating women, or patients unwilling to use effective contraception during Gecacitinib treatment and for 1 week after the last dose.
• Inability to swallow oral tablets.

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

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07476872 · IIT2026016

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗