Ruxolitinib as add-on Therapy in Steroid-refractory Graft-vs-host Disease

Steroid Refractory GVHD Clinical Trial

Official title:

Ruxolitinib Add-on in Steroid-refractory Graft-vs-host Disease After Allogeneic Stem Cell Transplantation: a Single Institutional Experience

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05663827
• Other study ID #: RSR-1123
• Status: Completed
• Phase: Phase 3
• Start date: January 1, 2019
• Est. completion date: November 30, 2022

Study information

• Verified date: March 2024
• Source: Chang Gung Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Steroid-refractory graft-vs-host disease (SR-GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation (HSCT). We sought to evaluate the effect and safety of ruxolitinib (RUX) add-on in the treatment of patients with SR-GVHD.

Description:

Nowadays, second-line treatment for SR-GVHD differs between centers and depends on the physician's experience. The agents commonly used as second and further lines of therapy include anti-thymocyte globulin, mycophenolate mofetil, calcineurin inhibitor, or extracorporeal photopheresis. However, the response varied. This study highlighted that corticosteroid (CS) is not a panacea for treating GVHD, and some patients with remission still experience further relapse. Additionally, the identification of multiple infections adds complexity.

Hope was supposed to come in 2019 after the Food and Drug Administration (FDA) approved RUX for the therapy of SR-GVHD in adult and pediatric patients > 12 years. RUX add-on should be withheld as the risks outweigh the benefits, especially for patients who developed scleroderma and bronchiolitis obliterans. RUX can be added on as needed for the treatment of GVHD, especially in patients receiving DLI as relapse therapy with the conversion from mixed chimerism to complete chimerism. Despite some studies showing the efficacy of RUX across affected organs, some other data bring the opposite results. Thus we conducted this study to reinforce the efficacy of RUX as an add-on therapy for SR-GVHD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: November 30, 2022
• Est. primary completion date: January 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 30 Years

Eligibility

Inclusion Criteria:

• Patients diagnosed with hematologic disorder

Exclusion Criteria:

• Those who are not applicable of receiving Ruxolitinib as immunodeficiency-modulation therapy

• Those who are actively encountering acute infectious illness

Related Conditions & MeSH terms

• Graft vs Host Disease
• Steroid Refractory GVHD

Intervention

Drug:
• Ruxolitinib
A dosage of 5mg once daily will be applied as initiation. After one week use, dose escalation or de-escalation would depend on clinical response.

Locations

Country	Name	City	State
Taiwan	Chang Gung Memorial Hospital	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Yi-Lun Wang

Country where clinical trial is conducted

Taiwan, 

References & Publications (3)

Malard F, Huang XJ, Sim JPY. Treatment and unmet needs in steroid-refractory acute graft-versus-host disease. Leukemia. 2020 May;34(5):1229-1240. doi: 10.1038/s41375-020-0804-2. Epub 2020 Apr 3. — View Citation

Przepiorka D, Luo L, Subramaniam S, Qiu J, Gudi R, Cunningham LC, Nie L, Leong R, Ma L, Sheth C, Deisseroth A, Goldberg KB, Blumenthal GM, Pazdur R. FDA Approval Summary: Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease. Onc — View Citation

Wolff D, Fatobene G, Rocha V, Kroger N, Flowers ME. Steroid-refractory chronic graft-versus-host disease: treatment options and patient management. Bone Marrow Transplant. 2021 Sep;56(9):2079-2087. doi: 10.1038/s41409-021-01389-5. Epub 2021 Jul 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GI symptoms secondary to GVHD	Diarrhea event exceeds a frequency of 5 times a day	3 years
Primary	Skin symptoms secondary to GVHD	Skin rash extends more than 25% of body surface area	3 years
Secondary	Overall survival	From diagnosis of SR-GVHD to mortality due to any cause	3 years