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

Overview

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

• Drug Rovadicitinib
  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.
• Drug Imatinib
  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.
• Drug Methotrexate
  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.
• Drug Mycophenolate mofetil
  Metoprolol ester is an organic compound mainly used as an immunosuppressant
• Drug Rituximab
  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.

Primary outcome measures

• Objective remission rate in the 24th week (ORR) [Time frame: Week 24]

Secondary outcome measures (12)

• Best Objective Response Rate (BOR) [Time frame: Week 24]
• Duration of Relief (DOR) [Time frame: Through study completion, an average of 2 year]
• Improvement in Lee cGVHD symptom score of subjects in week 24 [Time frame: Week 24]
• Failure free survival (FFS) [Time frame: Weeks 2, 4, 8, 16, 36, 48, 60, 72, 84, 96]
• Primary disease recurrence rate (MR) [Time frame: Weeks 8, 16,24， 36, 48]
• Non-Relapse Mortality (NRM) [Time frame: Weeks 8, 16,24， 36, 48]
• Overall survival (OS) [Time frame: Through study completion, an average of 2 year]
• Percentage of subjects whose daily glucocorticoid dose decreased [Time frame: Week 24]
• Changes in the Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) [Time frame: Through study completion, an average of 2 year]
• Changes in 5-level EQ-5D (EQ-5D-5L) [Time frame: Through study completion, an average of 2 year]
• Adverse events (AE) [Time frame: Through study completion, an average of 2 year]
• Cmax [Time frame: 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)]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 41 centers

• The First Affiliated Hospital of USTC Anhui Provincial Hospital — Hefei
• Peking University First Hospital — Beijing
• Peking University People's Hospital — Beijing
• The Southwest Hospital of AMU — Chongqing
• Fujian Medical University Union Hospital — Fuzhou
• The First Affiliated Hospital of Xiamen University — Xiamen
• The First Hospital of Lanzhou University — Lanzhou
• The 904 Hospital of the Joint Service Support Force of the People's Liberation Army of Chi — Lanzhou
• … and 33 more centers

Identifiers

NCT: NCT06682169 · TQ05105-III-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗