Basiliximab Combined With Ruxolitinib as Second-line Treatment of Grade 3-4 Steroid-resistant aGVHD

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Prospective Multicenter, Single-arm Clinical Study of Anti-CD25 Monoclonal Antibody Combined With Ruxolitinib in the Treatment of Grade 3-4 Steroid-resistant Acute Graft-versus-host Disease

Conditions
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Safety and Efficacy

Intervention / Treatment
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* Drug: Ruxolitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of primary grade 3-4(according to MAGIC criteria) steroid-resistant acute graft-versus-host disease(progression after 3 days or lack of improvement after 5 days of systemic 1.5-2 mg/kg steroids). Age 18-65. ECOG score≤3. Must be able to understand and willing to participate in the study and sign the informed consent. Exclusion Criteria: Refractory/secondary graft-versus-host disease. Severe complications such as myocardial infarction, chronic cardiac insufficiency, hepatic failure, renal insufficiency, etc. Clinically uncontrolled active infections. Other Malignant tumors with progression. Ecg: QT interval > 450 ms. Allergic to arsenic agent. Pregnant or lactating women. Expected survival <60 days. Undergoing other drug clinical trials.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ruxolitinib+basiliximab<br>Patients with grade 3-4 steroid-refractory aGVHD receive combined therapy of basiliximab and ruxolitinib. | Drug: Ruxolitinib<br>* Ruxolitinib and basiliximab are both second-line treatment for grade 3-4 steroid-resistant acute graft-versus-host disease.<br>* Other names: basiliximab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall 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. | day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR at d14/d56 | overall response rate at day 14/56 | 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. | 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. | 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. | 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. | 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 | through study completion, an average of 1 year | 
| incidence rated of chronic GVHD | incidence rated of chronic GVHD | through study completion, an average of 1 year |