Safety and Efficacy
Conditions
Brief summary
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
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.
Interventions
DRUGRuxolitinib
Ruxolitinib and basiliximab are both second-line treatment for grade 3-4 steroid-resistant acute graft-versus-host disease.
Sponsors
Soochow Hopes Hematonosis Hospital
The Second People's Hospital of Huai'an
The First Affiliated Hospital of Soochow University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| overall response rate at day 28 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to response | through study completion(median 12 days according to previous study) | Time to response, defined as time from the day treatment initiates to the date of first documentation PR or CR. |
| Duration of response | through study completion, an average of 1year | 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. |
| OS | through study completion, an average of 1year | Overall survival (OS) defined as time from the day treatment initiates to the date of death from any cause. |
| ORR at d14/d56 | day 14, day 56 | overall response rate at day 14/56 |
| incidence rate of secondary grade 3-4 liver aGVHD | through study completion, an average of 1 year | incidence rate of secondary grade 3-4 liver aGVHD |
| incidence rated of chronic GVHD | through study completion, an average of 1 year | incidence rated of chronic GVHD |
| EFS | through study completion, an average of 1year | 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. |
Countries
China
Contacts
Primary ContactXuefeng He, doctor
Backup ContactFei Zhou, doctor
Outcome results
None listed