Clinical trial NCT05663827: Ruxolitinib as add-on Therapy in Steroid-refractory Graft-vs-host Disease
Official title: Ruxolitinib Add-on in Steroid-refractory Graft-vs-host Disease After Allogeneic Stem Cell Transplantation: a Single Institutional Experience
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Steroid Refractory GVHD
Keywords: acute lymphoblastic leukemia
hematopoietic stem cell transplantation
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2022-12-23
Enrollment: 6
Sex: ALL
Minimum age (years): 3
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Cases with steroid-refractory GVHD would be given an add-on therapy of age/weight adjusted dosage of Ruxolitinib
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: GI symptoms secondary to GVHD
timeFrame: 3 years
measure: Skin symptoms secondary to GVHD
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Division of Hematology/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital
name: Tang-Her Jaing
role: STUDY_DIRECTOR
References:
citation: 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.
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.
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. Oncologist. 2020 Feb;25(2):e328-e334. doi: 10.1634/theoncologist.2019-0627. Epub 2019 Oct 22.