Low Dose Ruxolitinib in Combination With Methylprednisolone

Phase 1

Completed

• Conditions: Stem Cell Transplant Complications; aGVHD
• Interventions: Drug: Ruxolitinib 5 mg twice a day combined with Corticosteroids; Drug: Ruxolitinib 5 mg once a day combined with Corticosteroids; Drug: Ruxolitinib 10 mg twice a day combined with Corticosteroids; Drug: Ruxolitinib 2.5 mg once a day combined with Corticosteroids

• Registration Number: NCT04397367
• Lead Sponsor: Chinese PLA General Hospital

Brief Summary

This study is to determine the efficacy and safety of combined Low dose Ruxolitinib With Methylprednisone as Initial Therapy for the aGVHD(acute graft-versus-host disease )

Detailed Description

Corticosteroid is used as a first-line treatment for acute GVHD. However, it is effective in only about half of patients. In this prospective study, the investigators prospectively combined low dose ruxolitinib and 1mg/kg methylprednisolone in the initial treatment of acute GVHD. In order to effectively control GVHD without exposing acute GVHD patients to more intense and prolonged immunosuppression, we used ruxolitinib (20mg/day, 10mg/day, 5mg/day, 2.5mg/day) combined with 1mg/kg methylprednisolone. To ally steroid-related complications, we decreased steroid exposure time (39 days) and cumulative methylprednisolone doses (15.4 mg/kg) to spare the associated toxicity of glucocorticoid therapy.

Study Timeline

• Study Start: 2019-01-01
• Study First Submitted: 2020-05-17
• Study First Submitted QC: 2020-05-17
• Study First Posted: 2020-05-21
• Primary Completion: 2020-07-01
• Study Completion: 2020-12-31
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-12
• Last Update Posted: 2021-12-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

1. diagnosed with hematological diseases.
2. Have undergone first allogeneic hematopoietic stem cell transplantation (allo-HSCT) from any donor source using bone marrow, peripheral blood stem cells, or cord blood for hematologic malignancies.
3. new onset of grade II~IV aGVHD or high risk aGVHD [based on suppression of tumorigenicity 2 (also ST2), Regenerating Islet Derived Protein 3 Alpha (also REG3a), experimental objects) within 100 days post-transplantation.

Exclusion Criteria

1. recipients of second allogeneic stem cell transplant.

2. acute GVHD induced by donor lymphocyte infusion, interferon.

3. received first line aGVHD treatment before enrollment.

4. overlap GVHD syndrome.

5. pregnant or breast-feeding women.

6. absolute neutrophil count (ANC) <0.5×10e9/L or platelet count (PLT) < 20×10e9/L

7. Serum creatinine > 2.0 mg/dL or creatinine clearance < 40 mL/min measured or calculated by Cockroft-Gault equation.

8. uncontrolled infection

9. human immunodeficiency virus infection

10. active hepatitis b virus, hepatitis C virus infection and need antivirus treatment.

11. Subjects with evidence of relapsed primary disease, or subjects who have been treated for relapse after the allo-HSCT was performed, or graft rejection.

12. allergic history to Janus kinase inhibitors.

13. Severe organ dysfunction unrelated to underlying GVHD, including:

    Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction). Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy. Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.

14. Received Janus kinase inhibitor therapy after allo-HSCT for any indication.

15. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Ruxolitinib5 mg twice a day combined with Corticosteroids	Ruxolitinib 5 mg twice a day combined with Corticosteroids	Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 5 mg twice a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.
Ruxolitinib5 mg once a day combined with Corticosteroids	Ruxolitinib 5 mg once a day combined with Corticosteroids	Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 5mg once a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.
Ruxolitinib10 mg twice a day combined with Corticosteroids	Ruxolitinib 10 mg twice a day combined with Corticosteroids	Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 10 mg twice a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.
Ruxolitinib 2.5 mg twice a day combined with Corticosteroids	Ruxolitinib 2.5 mg once a day combined with Corticosteroids	Newly diagnosed acute GVHD patients started therapy with methylprednisolone of 1 mg/kg/day after diagnosis. Ruxolitinib was administered at a median of 2 days after the use of methylprednisolone. Participants began oral administration of ruxolitinib at 2.5 mg once a day. Ruxolitinib was subsequently tapered due to the resolution of acute GVHD after three months of therapy. A dose-tapering schedule that would discontinue ruxolitinib in three months was recommended.

Primary Outcome Measures

Name	Time	Method
complete remission rate of acute GVHD 28 days after enrollment.	Day 28 after treatment	Defined as the proportion of participants demonstrating a complete response (CR), or partial response (PR) of acute GVHD

Secondary Outcome Measures

Name	Time	Method
the incidence of relapsed acute GVHD	Day 90 after treatment	Defined as the proportion of participants whose improved acute GVHD.
Six-month duration of response	Six-month after treatment	Defined as the time from first response until graft-versus-host disease (GVHD) progression or death. Duration of response will be assessed when all participants who are still on study complete the Day 180 visit.
Duration of response	Day 90 after treatment	Defined as the time from first response until GVHD progression or death, when all participants who are still on study complete the Day 90 visit.
Nonrelapse mortality (NRM)	6 months after treatment	Defined as the proportion of subjects who died due to causes other than malignancy relapse.
Relapse rate	2 years after treatment	Defined as the proportion of participants whose underlying malignancy relapsed.

Trial Locations

Locations (1)

Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China