Acute graft-versus-host disease (aGVHD) is the most common life-threatening complication of allogeneic hematopoietic stem cell transplantation. The recognized first-line treatment for grade 3-4 aGVHD is systemic glucocorticoid. However, there is no recognized second-line treatment for grade 3-4 steroid-resistant aGVHD (SR-aGVHD). The investigators try to observe the efficacy and safety of early application of anti-CD25 monoclonal antibody(basiliximab) combined with ruxotilinib in the treatment of severe SR-aGVHD.
Adults ages 18-65 with grade 3-4 SR-aGVHD Design Participants with grade 3-4 steroid-refractory acute GVHD (progression after 3 days or lack of improvement after 5 days of 1.5-2 mg/kg/d systemic steroids) receive combined therapy of basiliximab and ruxolitinib. Basiliximab is given 20mg twice a week for week 1, and then once a week until GVHD of the participants reaches grade 1(3 episodes for minimum). Ruxolitinib is given 5mg twice a day for one day and then escalates to 10mg twice a day if the participant is not administered with triazole antifungal agent. The drug dose will be adjusted according to participants' clinical manifestations, blood cell count, infection status and so on. For participants with lower gastrointestinal GVHD, intravenous cyclosporine or tacrolimus is given and plasma concentration is monitored in a safe and effective range. Best supportive treatment is given, including broad-spectrum anti-infection, nutrition support, and blood transfusion. The investigators access the efficacy and safety of second-line therapy once a week from day 14 until complete remission is received. Then the investigators access the hematological disease status, aGVHD, cGVHD, infection state once a month.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Ruxolitinib and basiliximab are both second-line treatment for grade 3-4 steroid-resistant acute graft-versus-host disease.
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
RECRUITINGoverall response rate at day 28
The primary endpoint is the overall response rate (ORR) at day 28 defined as proportion of patients demonstrating partial (PR) or complete response (CR) without requirement for additional systemic immunosuppressive therapy (IST) at day 28 after second-line treatment initiates.
Time frame: day 28
ORR at d14/d56
overall response rate at day 14/56
Time frame: day 14, day 56
Time to response
Time to response, defined as time from the day treatment initiates to the date of first documentation PR or CR.
Time frame: through study completion(median 12 days according to previous study)
Duration of response
Duration of response, assessed for responders only by calculating the time from first response to the date of first observation of aGvHD relapse/progression or the date of additional IST for GvHD.
Time frame: through study completion, an average of 1year
OS
Overall survival (OS) defined as time from the day treatment initiates to the date of death from any cause.
Time frame: through study completion, an average of 1year
EFS
Event-free survival (EFS) defined as the time from the day treatment initiates to the date of recurrence of underlying hematologic disease, graft failure or death due to any cause.
Time frame: through study completion, an average of 1year
incidence rate of secondary grade 3-4 liver aGVHD
incidence rate of secondary grade 3-4 liver aGVHD
Time frame: through study completion, an average of 1 year
incidence rated of chronic GVHD
incidence rated of chronic GVHD
Time frame: through study completion, an average of 1 year
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