Low-Dose ATG/PTCy Plus Ivarmacitinib for aGVHD Prevention in Haplo-PBSCT From Parous Female Donors

NCT07570745 | Recruiting Phase 2 DMC

• 1 other identifier: SHSYXY-PARITY-aGVHD-20251007
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bone Marrow Transplantation; Graft-Versus-Host Disease(GVHD)

Keywords

Graft-versus-host disease; Haploidentical transplantation; Low-dose ATG/PTCy; JAK1 inhibitor (Ivarmacitinib / SHR0302)

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Grades II-IV Acute GVHD

  Acute graft-versus-host disease (aGVHD) will be assessed according to standard criteria (Glucksberg or MAGIC). The primary measure is the occurrence of grade II-IV aGVHD in any organ (skin, liver, gastrointestinal tract) within 180 days after haploidentical peripheral blood stem cell transplantation. Severity will be graded based on clinical manifestations, laboratory results, and endoscopic or biopsy findings where applicable.

  From Day 0 to Day 180 post-transplant

Secondary Outcomes (2)

• Number of Participants With Graft Failure

  Day 28 post-transplant

• Number of Participants With Non-Relapse Mortality by Day +180

  Up to 180 days post-transplant

Other Outcomes (6)

• Number of Participants With Chronic Graft-Versus-Host Disease by 1 Year

  Up to 1 year post-transplant

• Number of Participants With Relapse by 1 Year

  Up to 1 year post-transplant

• Number of Participants Alive at 1 Year

  Up to 1 year post-transplant

Study Arms (1)

Low-dose ATG + PTCy + Ivarmacitinib

EXPERIMENTAL

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

Drug: Low-dose ATG + PTCy + Ivarmacitinib

Interventions

Low-dose ATG + PTCy + Ivarmacitinib DRUG

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

Low-dose ATG + PTCy + Ivarmacitinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: lead

Study Sites (1)

Shanghai General Hospital Affiliated to Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, 210000, China

RECRUITING

Related Publications (10)

• He Q, Sun X, Niu J, Yang J, Wang Y, Huang C, Zhou K, Tong Y, Cai Y, Dong B, Wan L, Song X, Qiu H. A Novel JAK1 Inhibitor SHR0302 Combined With Prednisone for First-Line Treatment of Chronic Graft-Versus-Host Disease: A Phase I Clinical Trial. Cell Transplant. 2024 Jan-Dec;33:9636897241254678. doi: 10.1177/09636897241254678.

  PMID: 38798038 BACKGROUND

• Sun X, He Q, Yang J, Wang A, Zhang F, Qiu H, Zhou K, Wang P, Ding X, Yuan X, Li H, Zhang Y, Song X. Preventive and Therapeutic Effects of a Novel JAK Inhibitor SHR0302 in Acute Graft-Versus-Host Disease. Cell Transplant. 2021 Jan-Dec;30:9636897211033778. doi: 10.1177/09636897211033778.

  PMID: 34269100 BACKGROUND

• Schroeder MA, Khoury HJ, Jagasia M, Ali H, Schiller GJ, Staser K, Choi J, Gehrs L, Arbushites MC, Yan Y, Langmuir P, Srinivas N, Pratta M, Perales MA, Chen YB, Meyers G, DiPersio JF. A phase 1 trial of itacitinib, a selective JAK1 inhibitor, in patients with acute graft-versus-host disease. Blood Adv. 2020 Apr 28;4(8):1656-1669. doi: 10.1182/bloodadvances.2019001043.

  PMID: 32324888 BACKGROUND

• Kim S, Ashami K, Lim S, Staser K, Vij K, Santhanam S, Ritchey J, Peterson S, Gao F, Ciorba MA, Cooper ML, DiPersio JF, Choi J. Baricitinib prevents GvHD by increasing Tregs via JAK3 and treats established GvHD by promoting intestinal tissue repair via EGFR. Leukemia. 2022 Jan;36(1):292-295. doi: 10.1038/s41375-021-01360-9. Epub 2021 Jul 24. No abstract available.

  PMID: 34304247 BACKGROUND

• Loren AW, Bunin GR, Boudreau C, Champlin RE, Cnaan A, Horowitz MM, Loberiza FR, Porter DL. Impact of donor and recipient sex and parity on outcomes of HLA-identical sibling allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2006 Jul;12(7):758-69. doi: 10.1016/j.bbmt.2006.03.015.

  PMID: 16785065 BACKGROUND

• Yang J Sr, Jia Y, Hu X, Zhou F, Ni X, Wan J, Ding Y, Kang M, Yu X, Jiang C, Wang L, Wan L, Cai Y, Huang C, Qiu H, Ding X, Tong Y, Dong B, Zhou K, Song X. Randomized trial of GvHD Prophylaxis in Haploidentical PBSC Transplantation: ATG, PTCy, and Low-Dose Combination Therapy. Blood. 2026 Mar 18:blood.2025032569. doi: 10.1182/blood.2025032569. Online ahead of print.

  PMID: 41849227 BACKGROUND

• Xu X, Yang J, Cai Y, Li S, Niu J, Zhou K, Jiang Y, Xu X, Shen C, Huang C, Qiu H, Wei D, Kang M, Tong Y, Wei Z, Liu P, Wan L, Song X. Low dose anti-thymocyte globulin with low dose posttransplant cyclophosphamide (low dose ATG/PTCy) can reduce the risk of graft-versus-host disease as compared with standard-dose anti-thymocyte globulin in haploidentical peripheral hematopoietic stem cell transplantation combined with unrelated cord blood. Bone Marrow Transplant. 2021 Mar;56(3):705-708. doi: 10.1038/s41409-020-01047-2. Epub 2020 Sep 1. No abstract available.

  PMID: 32873913 BACKGROUND

• Cooke KR, Luznik L, Sarantopoulos S, Hakim FT, Jagasia M, Fowler DH, van den Brink MRM, Hansen JA, Parkman R, Miklos DB, Martin PJ, Paczesny S, Vogelsang G, Pavletic S, Ritz J, Schultz KR, Blazar BR. The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2017 Feb;23(2):211-234. doi: 10.1016/j.bbmt.2016.09.023. Epub 2016 Oct 3.

  PMID: 27713092 BACKGROUND

• Blazar BR, Murphy WJ, Abedi M. Advances in graft-versus-host disease biology and therapy. Nat Rev Immunol. 2012 May 11;12(6):443-58. doi: 10.1038/nri3212.

  PMID: 22576252 BACKGROUND

• Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009 May 2;373(9674):1550-61. doi: 10.1016/S0140-6736(09)60237-3. Epub 2009 Mar 11.

  PMID: 19282026 BACKGROUND

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

ivarmacitinib

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Xianmin Song, PhD

  Shanghai General Hospital Affiliated to Shanghai Jiao Tong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xianmin Song, PhD

CONTACT

+021-63240090; shongxm@sjtu.edu.cn

Xianmin Song, PhD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Department Director

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: May 6, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)