Low-dose ATG/PTCy plus ivarmacitinib to prevent acute GVHD after haploidentical PBSC transplant 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

This tests whether adding the oral JAK1 inhibitor ivarmacitinib to low-dose ATG and post‑transplant cyclophosphamide can prevent acute GVHD in adults receiving haploidentical peripheral blood stem cell transplants from parous female donors.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 82 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (Academic / other)
• Drugs / interventions: chemotherapy, Ivarmacitinib, methotrexate, cyclophosphamide, ruxolitinib, baricitinib, itacitinib
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07570745 on ClinicalTrials.gov

What this trial studies

Acute GVHD remains a major complication after haploidentical peripheral blood stem cell transplantation, especially when the donor is a parous female. This phase 2 interventional protocol combines low-dose anti-thymocyte globulin (ATG) and post‑transplant cyclophosphamide (PTCy) with oral ivarmacitinib, a selective JAK1 inhibitor, given around the time of transplant as GVHD prophylaxis. The trial tests the safety and preliminary efficacy of this three-part regimen in reducing early aGVHD and subsequent chronic GVHD. Key outcomes include incidence of grade II–IV aGVHD by day 100, safety/toxicity, and measures of GVHD‑free survival.

Who should consider this trial

Good fit: Adults aged 18–70 with hematologic malignancies planned for haploidentical peripheral blood stem cell transplantation from a healthy parous female haploidentical donor who meet standard organ‑function and performance‑status criteria.

Not a fit: Patients receiving matched donors or non‑parous donors, those with uncontrolled infections or severe organ dysfunction, or people not undergoing haploidentical PBSC transplantation are unlikely to benefit from this specific prophylaxis approach.

Why it matters

Potential benefit: If successful, the regimen could reduce rates of moderate-to-severe acute GVHD and improve GVHD‑free survival after haploidentical PBSC transplantation in this high‑risk donor subgroup.

How similar studies have performed: Previous studies combining low‑dose ATG with PTCy have lowered GVHD rates in haploidentical transplants and JAK inhibitors (e.g., ruxolitinib) are effective for treating GVHD, but using a selective JAK1 inhibitor like ivarmacitinib for prophylaxis in this donor subgroup is relatively novel with only early supportive data.

Eligibility criteria

Inclusion Criteria:

1. 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).
2. 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.
3. 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.
4. 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.
5. No significant psychiatric disorders; able to understand and voluntarily consent to participate in the study.
6. The patient has signed the informed consent form and agrees to comply with follow-up and related examinations.

Exclusion Criteria:

1. History of prior hematopoietic stem cell transplantation (including autologous or allogeneic transplant).
2. Presence of donor-specific antibodies (DSA) with a mean fluorescence intensity (MFI) ≥5000.
3. History of severe hypersensitivity or allergy to JAK inhibitors or the investigational drug.
4. Prior treatment with JAK1/2 inhibitors.
5. 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.
6. 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).

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai General Hospital Affiliated to Shanghai Jiao Tong University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Xianmin Song, PhD — Shanghai General Hospital Affiliated to Shanghai Jiao Tong University
• Study coordinator: Xianmin Song, PhD

Conditions Graft-Versus-Host Disease; Bone Marrow Transplantation; Graft-versus-host disease; Haploidentical transplantation; Low-dose ATG/PTCy; JAK1 inhibitor