Low Dose Ruxolitinib in Combination With Methylprednisolone

NCT ID: NCT04397367

Last Updated: 2021-12-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-01

Study Completion Date

2020-12-31

Brief Summary

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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

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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.

Conditions

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aGVHD Stem Cell Transplant Complications

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Ruxolitinib10 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.

Group Type EXPERIMENTAL

Ruxolitinib 10 mg twice a day combined with Corticosteroids

Intervention Type DRUG

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.

Ruxolitinib5 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.

Group Type EXPERIMENTAL

Ruxolitinib 5 mg twice a day combined with Corticosteroids

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Ruxolitinib 5 mg once a day combined with Corticosteroids

Intervention Type DRUG

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 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.

Ruxolitinib 2.5 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 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.

Group Type EXPERIMENTAL

Ruxolitinib 2.5 mg once a day combined with Corticosteroids

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

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 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.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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ruxolitinib 10 mg twice a day ruxolitinib 5 mg twice a day Ruxolitinib 5 mg once a day Ruxolitinib 2.5 mg once a day

Eligibility Criteria

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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.
Minimum Eligible Age

14 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chinese PLA General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Daihong Liu

Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Daihong Liu

Role: PRINCIPAL_INVESTIGATOR

Chinese PLA General Hospital

Locations

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Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Site Status

Countries

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China

References

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Dou LP, Li HH, Wang L, Li F, Huang WR, Yu L, Liu DH. Efficacy and Safety of Unmanipulated Haploidentical Related Donor Allogeneic Peripheral Blood Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Myeloid Leukemia. Chin Med J (Engl). 2018 Apr 5;131(7):790-798. doi: 10.4103/0366-6999.228243.

Reference Type BACKGROUND
PMID: 29578122 (View on PubMed)

Sandmaier BM, Kornblit B, Storer BE, Olesen G, Maris MB, Langston AA, Gutman JA, Petersen SL, Chauncey TR, Bethge WA, Pulsipher MA, Woolfrey AE, Mielcarek M, Martin PJ, Appelbaum FR, Flowers MED, Maloney DG, Storb R. Addition of sirolimus to standard cyclosporine plus mycophenolate mofetil-based graft-versus-host disease prophylaxis for patients after unrelated non-myeloablative haemopoietic stem cell transplantation: a multicentre, randomised, phase 3 trial. Lancet Haematol. 2019 Aug;6(8):e409-e418. doi: 10.1016/S2352-3026(19)30088-2. Epub 2019 Jun 24.

Reference Type BACKGROUND
PMID: 31248843 (View on PubMed)

Ruutu T, Gratwohl A, Niederwieser D, de Witte T, van der Werf S, van Biezen A, Mohty M, Kroger N, Rambaldi A, McGrath E, Sureda A, Basak G, Greinix H, Duarte RF. The EBMT-ELN working group recommendations on the prophylaxis and treatment of GvHD: a change-control analysis. Bone Marrow Transplant. 2017 Mar;52(3):357-362. doi: 10.1038/bmt.2016.298. Epub 2016 Nov 28.

Reference Type RESULT
PMID: 27892949 (View on PubMed)

Akahoshi Y, Igarashi A, Fukuda T, Uchida N, Tanaka M, Ozawa Y, Kanda Y, Onizuka M, Ichinohe T, Tanaka J, Atsuta Y, Kako S; Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation. Impact of graft-versus-host disease and graft-versus-leukemia effect based on minimal residual disease in Philadelphia chromosome-positive acute lymphoblastic leukemia. Br J Haematol. 2020 Jul;190(1):84-92. doi: 10.1111/bjh.16540. Epub 2020 Mar 2.

Reference Type RESULT
PMID: 32119132 (View on PubMed)

Yeshurun M, Weisdorf D, Rowe JM, Tallman MS, Zhang MJ, Wang HL, Saber W, de Lima M, Sandmaier BM, Uy G, Kamble RT, Cairo MS, Cooper BW, Cahn JY, Ganguly S, Camitta B, Verdonck LF, Dandoy C, Diaz MA, Savani BN, George B, Liesveld J, McGuirk J, Byrne M, Grunwald MR, Drobyski WR, Pulsipher MA, Abdel-Azim H, Prestidge T, Wieduwilt MJ, Martino R, Norkin M, Beitinjaneh A, Seo S, Nishihori T, Wirk B, Frangoul H, Bashey A, Mori S, Marks DI, Bachanova V. The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia. Blood Adv. 2019 Feb 26;3(4):670-680. doi: 10.1182/bloodadvances.2018027003.

Reference Type RESULT
PMID: 30808685 (View on PubMed)

Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, Spoerl S, Ditschkowski M, Ecsedi M, Sockel K, Ayuk F, Ajib S, de Fontbrune FS, Na IK, Penter L, Holtick U, Wolf D, Schuler E, Meyer E, Apostolova P, Bertz H, Marks R, Lubbert M, Wasch R, Scheid C, Stolzel F, Ordemann R, Bug G, Kobbe G, Negrin R, Brune M, Spyridonidis A, Schmitt-Graff A, van der Velden W, Huls G, Mielke S, Grigoleit GU, Kuball J, Flynn R, Ihorst G, Du J, Blazar BR, Arnold R, Kroger N, Passweg J, Halter J, Socie G, Beelen D, Peschel C, Neubauer A, Finke J, Duyster J, von Bubnoff N. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015 Oct;29(10):2062-8. doi: 10.1038/leu.2015.212. Epub 2015 Jul 31.

Reference Type RESULT
PMID: 26228813 (View on PubMed)

Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, Gallagher G, Kerr H, Kuruvilla J, Lee SJ, Moore J, Nevill T, Popradi G, Roy J, Schultz KR, Szwajcer D, Toze C, Foley R; Cell Therapy Transplant Canada. Addition of anti-thymocyte globulin to standard graft-versus-host disease prophylaxis versus standard treatment alone in patients with haematological malignancies undergoing transplantation from unrelated donors: final analysis of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2020 Feb;7(2):e100-e111. doi: 10.1016/S2352-3026(19)30220-0. Epub 2020 Jan 17.

Reference Type RESULT
PMID: 31958417 (View on PubMed)

Other Identifiers

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S-2019-177-01

Identifier Type: -

Identifier Source: org_study_id