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).
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: 1. Determining the RP2D of gecacitinib (also known as jaktinib) in combination with glucocorticoids. 2. Assessing the safety profile (e.g., incidence and severity of adverse events). 3. 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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
This 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.
The First Affiliated Hospital, Zhejiang University School of Medicine.
Hangzhou, Zhejiang, China
RECRUITINGIncidence 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.
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 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.
Time frame: 28 days
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.
Time frame: 28 days
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.
Time frame: Weeks 1, 2, 6, 8, 12, and 24
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.
Time frame: 1 year
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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.
Time frame: 180 days
Change in levels of serum biomarkers
Change in levels of serum biomarkers from baseline to Days 7, 14, and 28 following treatment with Jaktinib in combination with corticosteroids.
Time frame: Days 7, 14, and 28
1-year GVHD-free, relapse-free survival (GRFS)
Defined as the proportion of subjects who are alive and free from relapse of the underlying malignancy and without active chronic GVHD requiring systemic immunosuppressive therapy at 1 year after treatment initiation.
Time frame: 1 year
1-year cumulative incidence of moderate-to-severe chronic graft-versus-host disease (cGVHD).
1-year cumulative incidence of moderate-to-severe chronic graft-versus-host disease (cGVHD).
Time frame: 1 year
Immune reconstitution at Weeks 4, 12, and 24 post-transplantation
Immune reconstitution at Weeks 4, 12, and 24 post-transplantation, as assessed by lymphocyte subset counts (CD3⁺ T cells, CD19⁺ B cells, CD56⁺ NK cells).
Time frame: Weeks 4, 12, and 24 post-transplantation