Gecacitinib Pre-, During- and Post-HSCT for Patients With Primary or Secondary Myelofibrosis

Official title

A Phase 2 Clinical Study of Gecacitinib in Peri-transplant Period of Hematopoietic Stem Cell Transplantation in Patients With Myelofibrosis (MF)

Overview

The investigators evaluate the efficacy and safety of Gecacitinib in patients with myelofibrosis (MF) before, during, and after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Interventions

• Drug Gecacitinib (also known as Jaktinib)
  Gecacitinib treatment is initiated or continued at least two weeks before transplantation (Day -14) at a dose of 50 mg bid. This dose is maintained during preconditioning and the transplantation period until hematopoietic reconstitution, after which the dose is increased to 100 mg bid once platelet count recovers to ≥50×10⁹/L and absolute neutrophil count (ANC) recovers to ≥0.5×10⁹/L. The 100 mg bid dose is maintained until six months post-transplantation, after which it is adjusted to 50 mg bid

Primary outcome measures

• 1-year GVHD-free and relapse-free survival (GRFS) rate from the date of transplant [Time frame: 1 year post-HSCT]

Secondary outcome measures (9)

• Cumulative incidence of aGVHD [Time frame: +100 days and 6 months post-HSCT]
• Cumulative incidence of cGVHD [Time frame: 6 months and 1 year post-HSCT]
• The molecular relapse rate of MF [Time frame: 1 year post-HSCT]
• Non-relapse mortality (NRM) rates [Time frame: 6 months and 1 year post-HSCT]
• Rate of Engraftment [Time frame: 100 days post-HSCT]
• Proportion of patients with baseline splenomegaly achieving a ≥35% reduction in spleen volume. [Time frame: 100 days, 6 months, and 1 year post-HSCT]
• Overall Survival [Time frame: 1 year post-HSCT]
• Progression Free Survival (PFS) [Time frame: 1 year post-HSCT]
• Toxicity rate [Time frame: From the first dose to 28 days after the last dose.]

Eligibility criteria

Inclusion criteria

• Aged 18-75 years, regardless of gender;
• Diagnosis of primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV-MF), or post-essential thrombocythemia myelofibrosis (post-ET-MF) according to the 2022 WHO diagnostic criteria;
• Meeting the criteria for intermediate-risk or high-risk groups per the DIPSS-plus classification;
• Scheduled to undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT), including transplants from HLA-matched or mismatched related or unrelated donors;
• ECOG performance status ≤2 and Karnofsky performance status ≥60%;
• Capable of understanding and signing the informed consent form, and able to comply with study and follow-up procedures.

Exclusion criteria

• Patients using other JAK inhibitors (except for Gecacitinib) at the time of screening may be enrolled if they switch to Gecacitinib treatment prior to screening.
• Patients who have previously undergone allogeneic hematopoietic stem cell transplantation or organ transplantation.
• Disease progression to accelerated or blast phase (peripheral blood or bone marrow blast percentage ≥10% at any time prior to transplantation).
• Presence of significant medical conditions or marked organ dysfunction that cannot be adequately controlled and may affect the completion of this study:

• Congestive heart failure classified as New York Heart Association (NYHA) Class III-IV, or documented history of diastolic or systolic dysfunction (e.g., LVEF <40% measured by echocardiography), or uncontrolled or unstable angina or myocardial infarction.
• Uncontrolled diabetes (>250 mg/dL or >13.9 mmol/L).
• Hypertension that cannot be reduced to the following range despite combination antihypertensive therapy (systolic blood pressure <160 mmHg, diastolic blood pressure <100 mmHg).
• Peripheral neuropathy (≥ Grade 2 per NCI-CTC AE v5.0 criteria).
• Serum creatinine >1.5 × ULN.
• ALT or AST >2.5 × ULN, or DBIL or TBIL >2.0 × ULN.
• Patients with any bacterial, viral, or fungal infection not adequately controlled.
• HIV-positive at screening, or active hepatitis B virus infection (HBsAg-positive with HBV-DNA positivity or above the normal reference range), or HCV antibody-positive with HCV-RNA positivity.
• History of tuberculosis or positive interferon-gamma release assay at screening.
• Suspected hypersensitivity to Gecacitinib Hydrochloride, drugs of the same class, or any of their excipients.
• Pregnant or breastfeeding women, or patients unwilling to use effective contraception during Gecacitinib treatment and for one week after the last dose.
• Patients with any other comorbidities that may interfere with the study or a history of prior malignancies.
• Patients unable to take oral tablets.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07471503 · IIT2026005

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗