steroid-refractory graft-versus-host disease
Conditions
Interventions
Treatment group:baritinib 2 mg Qd
Ruxolitinib 10 mg BID (Historical control group):None
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Inclusion criteria
Inclusion criteria: 1. The morphologic examination of bone marrow cells, flow cytometry typing of leukemia, molecular biology detection, cytogenetic detection and other relevant monitoring were completed at the initial diagnosis, and the diagnosis of the primary disease was in line with the diagnostic criteria for The Diagnosis and Efficacy of Hematologic Diseases; 2. The patient underwent allogeneic HSCT and successfully underwent hematopoietic reconstruction (neutrophil absolute count > 0.5 x 10^9/L for three consecutive days; platelet count > 20 x 10^9/L for 7 consecutive days without the support of blood transfusion, chimeric rate of donor-derived hematopoietic > 95%); 3. In line with the diagnostic criteria for graft-versus-host disease (GVHD) GVHD can be divided into aGVHD and cGVHD.According to the NIH standard, aGVHD was classified into classic aGVHD occurring within 100 days after stem cell transplantation or donor lymphocyte transfusion and delayed aGVHD occurring after 100 days after stem cell transplantation or donor lymphocyte transfusion. The clinical manifestations of both were aGVHD symptoms.cGVHD can be divided into classic cGVHD which only includes the clinical manifestations of cGVHD and overlapping syndrome of clinical manifestations of both aGVHD and cGVHD. The diagnosis and grading criteria of aGVHD should be combined with the clinical manifestations and histopathological results of patients, and the diagnosis and grading should be carried out according to the skin surface area involved in rash, the level of total bilirubin in liver function, and the amount of diarrhea, etc., with reference to the Glucksberg standard.The diagnosis of cGVHD and severity score of each organ were performed according to NIH standard 2014 Edition, and cGVHD was classified into mild, moderate and severe.Mild cGVHD involved 1 or 2 organs with a maximum score of 1 and lung score of 0. Moderate cGVHD: 3 or more organs involved with a maximum score of 1, or 1 or more organs (excluding lungs) involved with a maximum score of 2, or lung score of 1; Severe cGVHD: one or more organs involved with a maximum score of 3, or lung scores of 2 or 3. The score of the articular and fascia can also be recorded by the P-ROM scale. 4. Aged >=18 years (Children were excluded from this study due to insufficient current data on the dosage or adverse events of baritinib in patients under 18 years; 5. Prior treatment failure was defined as the presence of at least one of the following criteria; For acute graft-versus-host disease: (1) Treatment with prednisone/prednisone/methylprednisone at a dose of at least 2 mg/kg and no response after at least 7 days of treatment; (2) Prednisone/Prednisolone/methylprednisolone was treated at a dose of at least 2mg/kg and progressed after at least 3 days of treatment; (3) Failure to reduce prednisone/prednisolone dose to = 0.5 mg/kg.d; (3) Prednisone could not be gradually reduced with 0.5 mg/kg.d. 6. Eastern Collaborative Oncology Group (ECOG) performance Score 50%; 7. Adequate organ function before transplantation is defined as follows: (1) Total bilirubin less than or equal to 1.5 times the upper normal limit, unless
Exclusion criteria
Exclusion criteria: 1. Uncontrolled underlying diseases; 2. Other cancers except non-melanoma skin cancer or carcinoma in situ of the cervix or breast; 3. Uncontrolled co-morbidities. This criteria includes but is not limited to persistent or active infections, autoimmune diseases, symptomatic congestive heart failure, unstable angina pectoris, unstable arrhythmias, acute kidney injury, or mental illness/social conditions that would limit compliance with study requirements. 4. Recent (less than 1 year from the start of screening) myocardial infarction or embolic stroke; 5. No history of thrombosis or known tendency to thrombosis.Induced and/or superficial DVTS qualify if they are treated and resolved at screening; 6. Active bleeding; 7. Uncontrolled bacterial, viral, or fungal infections; 8. Absolute neutrophil counts < 1 x 10^9/L, platelets < 50 x 10^9/L; 9. Must not have myelofibrosis or other disease known to significantly affect post-transplant implantation 10. Evidence of transplant-associated microangiopathy (TMA) (According to Jodele et al., 2015,Diagnostic criteria for TMA); 11. Known allergy to one or more investigational drugs (including Rucotinib, Baritinib) or any excipient; 12. Known HIV or active hepatitis B or C infection; 13. Pregnancy and/or lactation; 14. Currently receiving or having received any investigational drug in the 30 days prior to the first dose of investigational drug (Day 3).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective remission rate;Treatment related mortality; | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinical safety indicators (general consultation and physical examination items, vital signs, possible adverse reactions, toxic side effects, allergic reactions, etc.);Laboratory safety indicators (myelotoxicity, liver function, kidney function, cardiotoxicity, etc.); | — |
Countries
China
Contacts
Public ContactXinchuan Chen
West China Hospital of Sichuan University
Outcome results
None listed