The Safety and Efficacy of Gecacitinib (Also Known as Jaktinib) Combined Glucocorticoids as First-line Treatment for Grade II-IV Acute Graft-versus-host Disease.
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- First Affiliated Hospital of Zhejiang University
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- Incidence of Adverse Reactions by Dosage Group in Patients with Grade II-IV Acute GVHD Treated with First-Line Gecacitinib (also known as Jaktinib) and corticosteroids
Overview
Brief Summary
This study aims to evaluate the optimal dose (Recommended Phase 2 Dose, RP2D), preliminary safety, and efficacy of gecacitinib (also known as jaktinib) in combination with glucocorticoids as first-line therapy for patients with grade II-IV acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Detailed Description
This study is a single-center, single-arm, prospective interventional trial utilizing a 3+3 dose escalation design to evaluate the safety and efficacy of first-line gecacitinib (also known as jaktinib) in combination with glucocorticoids for the treatment of grades II-IV acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).
A total of 35 patients will be enrolled across both the dose exploration phase (using the 3+3 design to determine the Recommended Phase 2 Dose [RP2D]) and the efficacy evaluation phase (where additional patients are treated at the RP2D to further assess efficacy and safety).
The primary objectives include:
- Determining the RP2D of gecacitinib (also known as jaktinib) in combination with glucocorticoids.
- Assessing the safety profile (e.g., incidence and severity of adverse events).
- Evaluating efficacy (e.g., overall response rate at Day 28). Secondary endpoints may include duration of response, survival outcomes, and biomarker analyses.
This design is appropriate for early-phase trials seeking to establish dosing and preliminary activity of a novel combination therapy in a high-risk population.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily provide signed informed consent and be ≥18 years of age at the time of consent.
- •Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) using bone marrow, peripheral blood stem cells, or umbilical cord blood.
- •Have received systemic glucocorticoid therapy for no more than 2 days prior to enrollment.
- •Demonstrate clear myeloid and platelet engraftment: absolute neutrophil count (ANC) \> 1.0 × 10⁹/L and platelet count \> 50 × 10⁹/L (permitted use of growth factors or transfusion support).
- •Clinical diagnosis of grade II-IV acute GVHD (aGVHD) per the MAGIC (Mount Sinai Acute GVHD International Consortium) criteria (Appendix 1).
- •ECOG performance status of 0-
- •Life expectancy \> 4 weeks.
- •Able to swallow tablets.
- •Willing and able to comply with study procedures and follow-up.
Exclusion Criteria
- •History of ≥2 allo-HSCT procedures.
- •Development of aGVHD following unplanned donor lymphocyte infusion (DLI) for relapse of underlying malignancy. Note: Planned DLI as part of the transplant protocol is permitted.
- •Concurrent treatment with another JAK inhibitor. Note: Patients who previously discontinued JAK inhibitors due to toxicity (not refractory aGVHD) are eligible.
- •Active bleeding.
- •Diagnosed or suspected chronic GVHD.
- •Uncontrolled active infection, defined as sepsis-induced hemodynamic instability or progressive symptoms/signs/imaging findings attributable to infection. Asymptomatic or persistent fever alone is not exclusionary.
- •unresolved toxicity or complications from allo-HSCT (excluding aGVHD).
- •Clinically significant abnormalities that may compromise safety, including: a) Uncontrolled diabetes (fasting glucose \>13.9 mmol/L); b) Hypertension unresponsive to ≥2 agents (systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg); c) Peripheral neuropathy ≥Grade 2 (per NCI CTCAE v5.0).
- •Within 6 months prior to screening: NYHA Class III/IV heart failure, unstable angina, myocardial infarction, cerebrovascular accident, or pulmonary embolism.
- •Arrhythmia requiring treatment or QTcB interval \>480 ms at screening.
Arms & Interventions
Gecacitinib (also known as Jaktinib) group
Patients accept Gecacitinib (also known as Jaktinib) combined glucocorticoids treatment
Intervention: Gecacitinib (also known as Jaktinib) combined glucocorticoids (Drug)
Outcomes
Primary Outcomes
Incidence of Adverse Reactions by Dosage Group in Patients with Grade II-IV Acute GVHD Treated with First-Line Gecacitinib (also known as Jaktinib) and corticosteroids
Time Frame: 28 days
The primary outcome of this study was the incidence of adverse reactions, stratified by Gecacitinib (also known as Jaktinib) dosage group, in patients diagnosed with grade II-IV acute graft-versus-host disease (GVHD) receiving first-line treatment with Gecacitinib (also known as Jaktinib) in combination with corticosteroids.
The Day 28 Overall Response Rate (ORR) in patients with grade II-IV acute graft-versus-host disease (GVHD) treated with Ggecacitinib (also known as Jaktinib) in combination with corticosteroids as first-line therapy.
Time Frame: 28 days
The Day 28 Overall Response Rate (ORR) in patients with grade II-IV acute graft-versus-host disease (GVHD) treated with Gecacitinib (also known as Jaktinib) in combination with corticosteroids as first-line therapy.
Secondary Outcomes
- To determine the Recommended Phase 2 Dose (RP2D) of Jaktinib for the efficacy evaluation phase.(28 days)
- Overall Response Rate (ORR) at Weeks 1, 2, 6, 8, 12, and 24 following treatment with Jaktinib in combination with corticosteroids.(Weeks 1, 2, 6, 8, 12, and 24)
- Duration of Response (DOR)(1 year)
- 180-day cumulative non-relapse mortality (NRM)(180 days)
- Change in levels of serum biomarkers(Days 7, 14, and 28)
- 1-year GVHD-free, relapse-free survival (GRFS)(1 year)
- 1-year cumulative incidence of moderate-to-severe chronic graft-versus-host disease (cGVHD).(1 year)
- Immune reconstitution at Weeks 4, 12, and 24 post-transplantation(Weeks 4, 12, and 24 post-transplantation)
Investigators
Yi Luo
Professor
First Affiliated Hospital of Zhejiang University