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).
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).
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.
Single group
Gecacitinib (also known as Jaktinib) combined glucocorticoids
DrugThis clinical trial employs a standard 3+3 design to establish the Recommended Phase 2 Dose (RP2D) of gecacitinib (also known as jaktinib) combined with methylprednisolone. The dose escalation begins at 50 mg QD. Based on the safety observed in the initial cohort of three subjects, the dose will either be escalated to 50 mg BID or the cohort will be expanded. The subsequent escalation level is to 150 mg QD. Throughout this phase, the methylprednisolone dose is adjusted per the investigator's assessment. After determining the RP2D, the study advances to an efficacy evaluation stage, where approximately 25 additional subjects are enrolled to receive the combination at the RP2D for a minimum of 28 days. The primary objective of the initial phase is to assess safety and tolerability, while the secondary goal of the expansion is to gather preliminary efficacy data on the combination regimen.
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
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.
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.
To determine the Recommended Phase 2 Dose (RP2D) of Jaktinib for the efficacy evaluation phase.
To determine the Recommended Phase 2 Dose (RP2D) of Jaktinib for the efficacy evaluation phase.
Overall Response Rate (ORR) at Weeks 1, 2, 6, 8, 12, and 24 following treatment with Jaktinib in combination with corticosteroids.
Overall Response Rate (ORR) at Weeks 1, 2, 6, 8, 12, and 24 following treatment with Jaktinib in combination with corticosteroids.
Duration of Response (DOR)
Defined as the time from the first achievement of response to disease progression of aGVHD, initiation of alternative systemic therapy, or death from any cause.
180-day cumulative non-relapse mortality (NRM)
Defined as the proportion of subjects who die from causes other than progression or relapse of the underlying hematologic malignancy within 180 days from treatment initiation.
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