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First Line Therapy for High Risk Acute GVHD

Sponsor
Chinese PLA General Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT04061876
Collaborator
LU DAOPEI MEDICAL (Other), 960th Hospital of PLA (Other), The Second Hospital of Hebei Medical University (Other)
198
Enrollment
1
Location
2
Arms
76.2
Anticipated Duration (Months)
2.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy and safety of combined Ruxolitinib With Corticosteroids as First Line Therapy for the Treatment of High risk aGVHD(acute graft-versus-host disease )

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Acute graft-versus-host disease (aGVHD) is treated with systemic corticosteroid immunosuppression as first line therapy. Many patients with high risk aGVHD do not respond to primary therapy, high-dose systemic corticosteroids; therefore, survival for those patients remains particularly poor. Here we determine the efficacy and safety of combined Ruxolitinib With Corticosteroids as First Line Therapy for the Treatment of High risk aGVHD.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
198 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Ruxolitinib in Combination With Corticosteroid as First Line Therapy for the Treatment of High Risk Acute Graft-Versus-Host Disease
Actual Study Start Date :
Aug 25, 2019
Anticipated Primary Completion Date :
Jan 1, 2023
Anticipated Study Completion Date :
Dec 30, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ruxolitinib combined with Corticosteroids

Participants began oral administration of ruxolitinib at 5 mg QD; Methylprednisolone: 1mg/kg/d , iv or iv gtt for at leas 5 days, then taper according to the clinical response.

Drug: Ruxolitinib
Participants began oral administration of ruxolitinib at 5 mg QD;Methylprednisolone: 1mg/kg/d , iv or iv gtt for at least 5 days, then taper according to the clinical response.
Other Names:
  • New

    • Drug: Corticosteroid
    Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 3 days, then taper according to the clinical response. 1mg/kg/d , iv or iv gtt for at least 5 days, then taper according to the clinical response.
    Other Names:
  • Traditional

    		•
    Active Comparator: Corticosteroids

    Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 1 week, then taper according to the clinical response.

    Drug: Corticosteroid
    Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 3 days, then taper according to the clinical response. 1mg/kg/d , iv or iv gtt for at least 5 days, then taper according to the clinical response.
    Other Names:
  • Traditional

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall response rate (ORR) at Day 28 [Day 28 after treatment]

      Defined as the proportion of participants demonstrating a complete response (CR), or partial response (PR).

    Secondary Outcome Measures

    1. 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. Six-month duration of response will be assessed when all participants who are still on study complete the Day 180 visit.

    2. 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.

    3. Nonrelapse mortality (NRM) [2 years after treatment]

      NRM was defined as death from any cause without relapse. Cumulative incidence of NRM was analyzed in a competing risk framework using Gray's method.

    4. Relapse rate [2 years after treatment]

      Defined as the proportion of participants whose underlying malignancy relapsed.Relapse was defined as hematologic recurrence of malignancies after transplantation. Cumulative incidence of relapse was analyzed in a competing risk framework using Gray's method.

    5. Disease-free survival (DFS) [2 years after treatment]

      Defined as the time from first dose of ruxolitinib to the earliest date that a participant died, had a relapse/progression of the underlying malignancy, required additional therapy for aGVHD, or demonstrated signs or symptoms of chronic graft-versus-host disease (cGVHD).DFS will be evaluated in an intent-to-treat analysis by Kaplan Meier estimate and Log Rank test. Survival will be calculated from the date of randomization.

    6. Overall survival (OS) [2 years after treatment]

      Defined as the time from study enrollment (first day of ruxolitinib treatment) to death due to any cause. OS will be evaluated in an intent-to-treat analysis by Kaplan Meier estimate and Log Rank test. Survival will be calculated from the date of randomization.

    7. GVHD-free and relapse-free survival (GRFS) [2 years after treatment]

      GRFS was defined as the time onset of grade 3 to 4 aGVHD, moderate to severe cGVHD, or relapse/disease progression/death. GRFS will be evaluated in an intent-to-treat analysis by Kaplan Meier estimate and Log Rank test. Survival will be calculated from the date of randomization.

    8. recurrence of aGVHD [1 years after treatment]

      Defined as the proportion of participants whose aGVHD relapsed.Relapse was defined as recurrence of new GVHD related symptoms after complete remission of aGVHD. Cumulative incidence of recurrence of aGVHD was analyzed in a competing risk framework using Gray's method.

    9. Failure-free survival [2 years after treatment]

      Failure-free survival (FFS) refers to the time from randomization to disease relapse or progression, non-relapse mortality, or the addition of new therapy for aGVHD.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    14 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 intermediate or high risk aGVHD (based on ST2, REG3a, other 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.

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

    2. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Chinese PLA General Hospital Beijing Beijing China 100853

    Sponsors and Collaborators

    • Chinese PLA General Hospital
    • LU DAOPEI MEDICAL
    • 960th Hospital of PLA
    • The Second Hospital of Hebei Medical University

    Investigators

    • Study Director: Daihong Liu, Chines PLA General Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Daihong Liu, Director, Chinese PLA General Hospital
    ClinicalTrials.gov Identifier:
    NCT04061876
    Other Study ID Numbers:
    • S2019-177-01
    First Posted:
    Aug 20, 2019
    Last Update Posted:
    May 27, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Daihong Liu, Director, Chinese PLA General Hospital
    aGVHD

    Study Results

    No Results Posted as of May 27, 2022