Low-Dose ATG/PTCy Plus Ivarmacitinib for aGVHD Prevention in Haplo-PBSCT From Parous Female Donors
Low-Dose ATG/PTCy Plus Ivarmacitinib to Prevent Acute Graft-versus-Host Disease Following Haploidentical Peripheral Blood Stem Cell Transplantation From Parous Female Donors: A Prospective, Single-Arm, Multicenter Trial
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
82 participants
May 1, 2026
INTERVENTIONAL
Conditions
Summary
Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), significantly affecting survival and quality of life. Acute GVHD (aGVHD) typically occurs within 100 days post-transplant, commonly involving skin, gastrointestinal tract, and liver. Chronic GVHD (cGVHD) can appear months to years later. Despite prophylaxis with calcineurin inhibitors (e.g., cyclosporine or tacrolimus), methotrexate, mycophenolate mofetil, and post-transplant cyclophosphamide (PTCy), patients receiving haploidentical transplantation from parous female donors remain at high risk for moderate-to-severe aGVHD. JAK1-dependent cytokine signaling (IL-6, IFN-γ) is central to GVHD pathogenesis. Selective JAK1 inhibition may attenuate T cell-mediated inflammation while preserving hematopoiesis. Ivarmacitinib (SHR0302) is a highly selective oral JAK1 inhibitor, showing favorable safety and preliminary efficacy in autoimmune and GVHD settings, making it a candidate for early GVHD prophylaxis.
Eligibility
Inclusion Criteria6
- Age 18-70 years, any gender. Recipients must be diagnosed with hematologic malignancies, such as acute leukemia, myelodysplastic syndrome, or malignant lymphoma, and are planned to undergo haploidentical peripheral blood stem cell transplantation (Haplo-PBSCT).
- The donor must be a haploidentical relative within three degrees of kinship and a parous female (having given birth; number of pregnancies not limited), aged 18-55 years, in good health, and cleared by donor screening.
- Karnofsky performance status ≥70. The recipient is expected to tolerate transplant-related toxicity. Major organ functions must meet transplantation requirements: cardiac and pulmonary function essentially normal; liver function: ALT/AST <2× upper limit of normal, total bilirubin <1.5× upper limit of normal; renal function: creatinine clearance >50 mL/min.
- No active infection prior to transplantation (or infection effectively controlled). Chronic infections such as HBV, HCV, or syphilis must be stable under treatment; HBV DNA negative or receiving antiviral therapy is acceptable.
- No significant psychiatric disorders; able to understand and voluntarily consent to participate in the study.
- The patient has signed the informed consent form and agrees to comply with follow-up and related examinations.
Exclusion Criteria6
- History of prior hematopoietic stem cell transplantation (including autologous or allogeneic transplant).
- Presence of donor-specific antibodies (DSA) with a mean fluorescence intensity (MFI) ≥5000.
- History of severe hypersensitivity or allergy to JAK inhibitors or the investigational drug.
- Prior treatment with JAK1/2 inhibitors.
- Uncontrolled comorbidities prior to transplantation, such as uncontrolled hypertension, diabetes complications, or active gastrointestinal ulcer bleeding, which may increase unacceptable risk for trial participation as evaluated by investigators.
- Receipt of other investigational drugs within 2 weeks prior to transplantation (excluding standard chemotherapy), or simultaneous participation in other interventional clinical studies, or any other condition deemed by the investigator to make the patient unsuitable for study participation, including poor compliance or inability to complete follow-up (e.g., severe psychiatric disorders preventing cooperation).
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Interventions
Patients will receive rabbit ATG 2.5 mg/kg on Day -2 and -1 (total 5 mg/kg), post-transplant cyclophosphamide 50 mg/kg on Day +3, cyclosporine/MMF starting Day +4, and Ivarmacitinib 4 mg PO daily from Day -3 to +45, reduced to 2 mg PO daily from Day +46 to +60
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07570745