Graft-versus-host Disease
Conditions
Brief summary
The aim of this study is to demonstrate that in subjects with moderate to severe chronic graft-versus-host disease in the third line and beyond, the use of rosuvastatin compared to the protocol chosen by the researchers can significantly improve the objective response rate of subjects at week 24.
Interventions
DRUGRovadicitinib
Rovadicitinib is an inhibitor of Janus associated kinases (JAK) family and Rho associated kinases (ROCK). It can inhibit the sustained abnormal activation of the Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway and also inhibit Rho associated kinase 2 (ROCK2). The JAK 1-JAK 2 signaling pathway is a key step in causing inflammation and tissue damage in acute and chronic graft-versus-host disease.
DRUGImatinib
Imatinib tyrosine kinase inhibitor is a small molecule protein kinase inhibitor that has the ability to block one or more protein kinases. Clinically used for the treatment of chronic myeloid leukemia and malignant gastrointestinal stromal tumors.
DRUGMethotrexate
Methotrexate is an organic compound, mainly used as an anti folate anti-tumor drug. It inhibits the synthesis of tumor cells by inhibiting dihydrofolate reductase, thereby inhibiting the growth and reproduction of tumor cells.
DRUGMycophenolate mofetil
Metoprolol ester is an organic compound mainly used as an immunosuppressant
DRUGRituximab
Rituximab activates antibody dependent cell-mediated phagocytosis and complement dependent cytotoxicity by binding to cluster of differentiation 20 (CD20) antigen, clearing malignant B cells expressing CD20 and achieving therapeutic goals.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18 to 70 years old; Karnofsky (KPS) ≥ 60 points; Expected survival period exceeding 6 months; * Previously received allogeneic hematopoietic stem cell transplantation; * According to NIH standards, the clinical diagnosis is moderate to severe cGVHD； * Previously received systematic treatment for cGVHD with 2-5 lines; * Stable dosage of corticosteroids and other immunosuppressants received within 2 weeks prior to screening; * The main organ functions well; * Starting from Day 1 after enrollment in the control group of this study, participants must receive one of the drugs specified in the study protocol; * Female participants of childbearing age should agree to use contraceptive measures (such as intrauterine devices, birth control pills, or condoms) during the study period and for 6 months after the end of the study; Serum pregnancy test negative within 7 days prior to enrollment in the study, and must be a non lactating subject; Male participants should agree to use contraceptive measures during the study period and within 6 months after the end of the study period; * Subjects voluntarily joined this study, signed informed consent, and had good compliance.
Exclusion criteria
* Has experienced or currently suffers from other malignant tumors within the past 3 years; * Known or suspected active aGVHD； * Individuals with interstitial pneumonia, non infectious pneumonia, uncontrolled active infections, or infections requiring systematic treatment within the first 7 days of randomization, except for those deemed suitable for inclusion by the researchers; * The occurrence and progression of other underlying diseases include post transplant lymphoid tissue proliferative diseases and recurrence of primary malignant hematological diseases; * Random failure of allogeneic hematopoietic stem cell transplantation within the first 6 months or having received 2 allogeneic hematopoietic stem cell transplants in the past; * Used JAK inhibitors, Bruton's tyrosine kinase (BTK) inhibitors, etc. within the first 2 weeks of randomization; * There are multiple factors that can affect oral medication, such as inability to swallow, intestinal obstruction, etc; * Individuals with a history of abuse of psychotropic drugs who are unable to quit or have mental disorders; * Subjects with any severe and/or uncontrolled illnesses; * Individuals who are allergic to research drugs or their components; * Participated in other clinical trials within the first 4 weeks of randomization; * According to the researcher's judgment, there are accompanying diseases that seriously endanger the safety of the subjects or affect the completion of the study, or subjects who are deemed unsuitable for inclusion due to other reasons.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective remission rate in the 24th week (ORR) | Week 24 | Researchers evaluated each organ according to the consensus criteria of the NIH 2014 conference, and at week 24, the percentage of subjects with complete response (CR) or partial response (PR) in all assessable organs was determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Relief (DOR) | Through study completion, an average of 2 year | The duration of symptom relief for patients after receiving treatment |
| Improvement in Lee cGVHD symptom score of subjects in week 24 | Week 24 | The Lee cGVHD Symptom Score is a tool used to assess the severity of symptoms in chronic graft-versus-host disease (cGVHD), ranging from 0 to 4 points, with a maximum total score of 16 points. The higher the score, the more severe the cGVHD symptoms. |
| Failure free survival (FFS) | Weeks 2, 4, 8, 16, 36, 48, 60, 72, 84, 96 | The time from the start of treatment to the occurrence of disease progression or death for any reason in the patient |
| Primary disease recurrence rate (MR) | Weeks 8, 16,24， 36, 48 | The probability of recurrence of the patient's disease within a certain period of time. |
| Non-Relapse Mortality (NRM) | Weeks 8, 16,24， 36, 48 | NRM was defined as death without recurrent or progressive disease |
| Overall survival (OS) | Through study completion, an average of 2 year | From randomization to the time of death caused by any reason |
| Best Objective Response Rate (BOR) | Week 24 | The best therapeutic effect among all therapeutic outcomes |
| Changes in the Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) | Through study completion, an average of 2 year | The FACT-BMT scale is a tool used to evaluate the quality of life (QOL) of patients after hematopoietic stem cell transplantation, the scale is filled out by the person closest to the patient, and each question has five possible answers on a scale of 0-4. Answer each question item based on the patient's actual situation in the past week, and mark the corresponding number with a √ |
| Changes in 5-level EQ-5D (EQ-5D-5L) | Through study completion, an average of 2 year | The scoring criteria of EQ-5D-5L scale include five dimensions: action ability, self-care ability, daily activity ability, pain or discomfort, anxiety or depression. After selecting a level for each dimension, a specific rating can be obtained. For example, if an individual chooses slightly difficult in terms of action ability, they will score 2 points on that dimension (from 0 to 5, where 0 indicates no difficulty and 5 indicates inability/very serious difficulty) |
| Adverse events (AE) | Through study completion, an average of 2 year | The incidence and severity of adverse events (AE) and serious adverse events (SAE), as well as abnormal laboratory test indicators. |
| Cmax | Day 1, day 8 on cycle 1: 0.5 hour pre-dose, 0.5 hour after dose, day 1 cycle 2: 0.5 hour pre-dose, 2 hours after dose, day 1 cycle 4: 0.5 hour pre-dose, 3 hours after dose, day 1 cycle 6: 0.5 hour pre-dose, 4 hours after dose (28 days as a cycle) | The maximum concentration of medication that enters the bloodstream after administration |
| Ctrough | Day 1, day 8 on cycle 1: 0.5 hour pre-dose, 0.5 hour after dose, day 1 cycle 2: 0.5 hour pre-dose, 2 hours after dose, day 1 cycle 4: 0.5 hour pre-dose, 3 hours after dose, day 1 cycle 6: 0.5 hour pre-dose, 4 hours after dose (28 days as a cycle) | After multiple administrations, the blood drug concentration reaches a relatively stable state, which is called the steady-state concentration |
| Percentage of subjects whose daily glucocorticoid dose decreased | Week 24 | Percentage of subjects whose daily glucocorticoid dose decreased by ≥ 50% in week 24, and percentage of subjects who discontinued all glucocorticoids |
Countries
China
Contacts
Primary ContactHe Huang, Doctor
Outcome results
None listed