First-Line Jaktinib for Acute Graft-Versus-Host Disease (aGVHD)

NCT07285889 | Recruiting Phase 1

• 1 other identifier: ZJU-GVHD-JAKTINIB1
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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).

Conditions

Acute Graft Versus Host Disease

Keywords

acute graft-versus-host disease; Jaktinib; hematopoietic stem cell transplantation; gecacitinib

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  28 days

Secondary Outcomes (8)

• 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

Study Arms (1)

Gecacitinib (also known as Jaktinib) group

EXPERIMENTAL

Patients accept Gecacitinib (also known as Jaktinib) combined glucocorticoids treatment

Drug: Gecacitinib (also known as Jaktinib) combined glucocorticoids

Interventions

Gecacitinib (also known as Jaktinib) combined glucocorticoids DRUG

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.

Also known as: gecacitinib (also known as jaktinib)

Gecacitinib (also known as Jaktinib) group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0-2.
• Life expectancy \> 4 weeks.
• Able to swallow tablets.
• Willing and able to comply with study procedures and follow-up.

You may not qualify if:

• 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.
• 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.
• Severe renal impairment (serum creatinine \>1.5 × ULN) at screening.
• Pre-transplant history of gastrointestinal ulcers, gastrectomy, or intestinal resection that may impair drug absorption.
• Major surgery within 4 weeks prior to screening without full recovery.
• Cholestatic disorders or hepatic sinusoidal obstruction syndrome (SOS/VOD) at screening (defined as persistent hyperbilirubinemia and organ dysfunction unrelated to GVHD).
• 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.
• History of active tuberculosis within 6 months prior to screening.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine.

Hangzhou, Zhejiang, China

RECRUITING

Related Publications (4)

• Moiseev IS, Morozova EV, Bykova TA, Paina OV, Smirnova AG, Dotsenko AA, Borzenkova ES, Galimov AN, Gudognikova YV, Ekushov KA, Kozhokar PV, Osipova AA, Pirogova OV, Rudakova TA, Klimova OU, Tcvetkov NY, Kulagin EA, Surkova EA, Lapin SV, Rodionov GG, Moiseev SI, Serov YA, Zubarovskaya LS, Afanasyev BV. Long-term outcomes of ruxolitinib therapy in steroid-refractory graft-versus-host disease in children and adults. Bone Marrow Transplant. 2020 Jul;55(7):1379-1387. doi: 10.1038/s41409-020-0834-4. Epub 2020 Feb 18.

  PMID: 32071418 RESULT

• Dignan FL, Clark A, Amrolia P, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Hadzic N, Shaw BE, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Diagnosis and management of acute graft-versus-host disease. Br J Haematol. 2012 Jul;158(1):30-45. doi: 10.1111/j.1365-2141.2012.09129.x. Epub 2012 Apr 26.

  PMID: 22533831 RESULT

• Zeiser R, von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R, Szer J, Wagner EM, Zuckerman T, Mahuzier B, Xu J, Wilke C, Gandhi KK, Socie G; REACH2 Trial Group. Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease. N Engl J Med. 2020 May 7;382(19):1800-1810. doi: 10.1056/NEJMoa1917635. Epub 2020 Apr 22.

  PMID: 32320566 RESULT

• Jagasia M, Perales MA, Schroeder MA, Ali H, Shah NN, Chen YB, Fazal S, Dawkins FW, Arbushites MC, Tian C, Connelly-Smith L, Howell MD, Khoury HJ. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood. 2020 May 14;135(20):1739-1749. doi: 10.1182/blood.2020004823.

  PMID: 32160294 RESULT

Study Officials

• Yi Luo

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

YIBO Wu, MD

CONTACT

+86057187233801; wuyibo7@126.com

Yi Luo

CONTACT

+86057187233801; luoyijr@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 3, 2025
• First Posted: December 16, 2025
• Study Start: December 3, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: 5 years
• Access Criteria: Access to the data will be granted following review and approval of a methodologically sound research proposal, in compliance with ethical standards and data protection regulations. Data sharing is subject to the execution of a data use agreement to ensure appropriate use and confidentiality.

Locations

CN (1)