First-line jaktinib plus corticosteroids for acute graft-versus-host disease

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.

This trial will test whether adding jaktinib to standard steroids helps adults with grade II–IV acute graft-versus-host disease after an allogeneic stem cell transplant.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: First Affiliated Hospital of Zhejiang University (Academic / other)
• Drugs / interventions: jaktinib, gecacitinib
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07285889 on ClinicalTrials.gov

What this trial studies

This is a single-center, single-arm, prospective phase 1/2 trial combining jaktinib (gecacitinib) with glucocorticoids as first-line therapy for grade II–IV aGVHD after allo-HSCT. An initial 3+3 dose-escalation phase will determine the recommended phase 2 dose (RP2D), followed by an efficacy expansion treating additional patients at the RP2D. A total of 35 patients will be enrolled to characterize safety, tolerability, and preliminary activity, with overall response rate at Day 28 a key efficacy endpoint. Secondary outcomes include duration of response, survival measures, and exploratory biomarker analyses.

Who should consider this trial

Good fit: Adults (≥18 years) who developed grade II–IV aGVHD after an allogeneic HSCT, have clear neutrophil and platelet engraftment, have started systemic glucocorticoids within the prior 2 days, and have ECOG 0–2 are ideal candidates.

Not a fit: Patients with a history of two or more allo-HSCTs, aGVHD following unplanned donor lymphocyte infusion, inadequate blood counts or other exclusion criteria are unlikely to qualify or benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could increase early response rates and potentially reduce reliance on high-dose steroids for patients with aGVHD.

How similar studies have performed: Other JAK inhibitors (for example ruxolitinib) have shown benefit in steroid-refractory aGVHD, but first-line use of jaktinib is relatively novel and is being tested to extend that approach to earlier treatment.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily provide signed informed consent and be ≥18 years of age at the time of consent.
2. Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) using bone marrow, peripheral blood stem cells, or umbilical cord blood.
3. Have received systemic glucocorticoid therapy for no more than 2 days prior to enrollment.
4. 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).
5. Clinical diagnosis of grade II-IV acute GVHD (aGVHD) per the MAGIC (Mount Sinai Acute GVHD International Consortium) criteria (Appendix 1).
6. ECOG performance status of 0-2.
7. Life expectancy \> 4 weeks.
8. Able to swallow tablets.
9. Willing and able to comply with study procedures and follow-up.

Exclusion Criteria:

1. History of ≥2 allo-HSCT procedures.
2. 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.
3. Concurrent treatment with another JAK inhibitor. Note: Patients who previously discontinued JAK inhibitors due to toxicity (not refractory aGVHD) are eligible.
4. Active bleeding.
5. Diagnosed or suspected chronic GVHD.
6. 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.
7. unresolved toxicity or complications from allo-HSCT (excluding aGVHD).
8. 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).
9. Within 6 months prior to screening: NYHA Class III/IV heart failure, unstable angina, myocardial infarction, cerebrovascular accident, or pulmonary embolism.
10. Arrhythmia requiring treatment or QTcB interval \>480 ms at screening.
11. Severe renal impairment (serum creatinine \>1.5 × ULN) at screening.
12. Pre-transplant history of gastrointestinal ulcers, gastrectomy, or intestinal resection that may impair drug absorption.
13. Major surgery within 4 weeks prior to screening without full recovery.
14. Cholestatic disorders or hepatic sinusoidal obstruction syndrome (SOS/VOD) at screening (defined as persistent hyperbilirubinemia and organ dysfunction unrelated to GVHD).
15. Active uncontrolled viral infections at screening: HBV: HBsAg⁺ with detectable HBV-DNA, or detectable HBV-DNA regardless of HBsAg status; HCV: Anti-HCV antibody⁺ with detectable HCV-RNA.
16. History of active tuberculosis within 6 months prior to screening.
17. Epilepsy or current use of psychotropic/sedative medications.
18. Pregnancy, lactation, or intention to conceive; male patients unwilling to use condoms during treatment and for 2 days after the last dose.
19. Other active malignancies (excluding the transplanted hematologic malignancy) within 5 years.
20. Current use of anticoagulants or antiplatelet agents (except low molecular weight heparin).
21. Any condition that, in the investigator's judgment, may compromise patient safety or protocol compliance.
22. Known hypersensitivity to jaktinib, its analogs, or excipients.
23. Participation in another interventional clinical trial within 4 weeks prior to screening.
24. Investigator determination of unsuitability for the study.

Where this trial is running

Hangzhou, Zhejiang

• The First Affiliated Hospital, Zhejiang University School of Medicine. — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Yi Luo — Zhejiang University
• Study coordinator: YIBO Wu, MD

Conditions Acute Graft Versus Host Disease; acute graft-versus-host disease; Jaktinib; hematopoietic stem cell transplantation; gecacitinib