Clinical trial NCT06682169: Evaluation of Rovadicitinib Compared to the Protocol Selected by Researchers in Third Line and Subsequent Studies of Moderate to Severe Chronic Graft-versus-host Disease
Official title: A Randomized, Open Label, Positive Controlled, Multicenter Phase III Clinical Trial Evaluating the Efficacy and Safety of the Selected Regimen of Rovadicitinib in Moderate to Severe Chronic Graft-versus-host Disease in Third Line and Beyond
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Graft-versus-host Disease
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-11-12
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective remission rate in the 24th week (ORR)
timeFrame: Week 24
Secondary outcomes:
measure: Best Objective Response Rate (BOR)
timeFrame: Week 24
measure: Duration of Relief (DOR)
timeFrame: Through study completion, an average of 2 year
measure: Improvement in Lee cGVHD symptom score of subjects in week 24
timeFrame: Week 24
measure: Failure free survival (FFS)
timeFrame: Weeks 2, 4, 8, 16, 36, 48, 60, 72, 84, 96
measure: Primary disease recurrence rate (MR)
timeFrame: Weeks 8, 16,24， 36, 48
measure: Non-Relapse Mortality (NRM)
timeFrame: Weeks 8, 16,24， 36, 48
measure: Overall survival (OS)
timeFrame: Through study completion, an average of 2 year
measure: Percentage of subjects whose daily glucocorticoid dose decreased
timeFrame: Week 24
measure: Changes in the Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT)
timeFrame: Through study completion, an average of 2 year
measure: Changes in 5-level EQ-5D (EQ-5D-5L)
timeFrame: Through study completion, an average of 2 year
measure: Adverse events (AE)
timeFrame: Through study completion, an average of 2 year
measure: Cmax
timeFrame: 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)
measure: Ctrough
timeFrame: 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)
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of USTC Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Chongqing
country: China
facility: The Southwest Hospital of AMU
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Lanzhou
country: China
facility: The 904 Hospital of the Joint Service Support Force of the People's Liberation Army of China
state: Gansu
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital The First People's Hospital Affiliated to Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical Hospital
state: Hebei
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The Third People's Hospital of Zhengzhou
state: Henan
city: Zhenzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Wuhan Union Hospital of China
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical College of HUST
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Huai'an
country: China
facility: Huai'an Second People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Tai'an
country: China
facility: Tai'an City Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Jiao Tong University School of Medicine，Renji Hospital
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School Of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Xi'an
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Chinese Academy of Medical Sciences Hematology Hospital
state: Tianjin
city: Ürümqi
country: China
facility: The First Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: The First People's Hospital of Yunnan Province
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Ningbo
country: China
facility: The Affiliated People's Hospital of Ningbo University
state: Zhejiang
city: Ningbo
country: China
facility: The First Affiliated Hospital of Ningbo University
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
References: