Ruxolitinib and Steroid As First Line Therapy for Acute GVHD

Ruxolitinib and Methylprednisolone As First Line Therapy for Acute Graft Versus Host Disease Following Allogeneic Stem Cell Transplantation

The purpose of this study is to evaluate the efficacy of ruxolitinib in combination with methylprednisolone as first line therapy in patients with Grades II to IV acute graft-versus-host disease (GVHD).

Study Overview

• Status: Terminated
• Conditions: Acute GVHD
• Intervention / Treatment: Drug: Ruxolitinib Oral Tablet; Drug: Methylprednisolone

Detailed Description

Treatment:

Once patients are diagnosed with grade II~IV acute GVHD, the combination therapy should be initiated as soon as possible.

1. Methylprednisolone: 2mg/kg/d, iv or iv gtt, in two or three divided doses. Taper steroid every one or two weeks according to patient's response.
2. Ruxolitinib 5~10mg bid po for at least 28 days. If patient's ANC<0.5×10e9/L or PLT< 20×10e9/L, cease ruxolitinib until recovery of ANC higher than 0.5×10e9/L or PLT higher than 20×10e9/L.

Indication for stopping Ruxolitinib treatment:

1. No response after ruxolitinib treatment for 28 days.
2. Develop life-threatening complication.
3. ANC<0.5×10e9/L or PLT< 20×10e9/L.

Indication for second line acute GVHD treatment:

1. deterioration of acute GVHD in 3 days
2. no response after 7 days
3. no complete remission after 2 weeks.

Suggestions of second line therapy:

Basiliximab 20mg, d1, d4, d8.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Shanghai General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. diagnosed with hematological diseases.
2. recipients of allogeneic peripheral blood stem cell transplantation.
3. new onset of grade II~IV acute graft versus host disease 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 treatment other than steroid 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. non-GVHD related liver dysfunction: glutamic pyruvic transaminase>= 4 times of upper normal limit, direct bilirubin >= 4 times of upper normal limit
8. renal dysfunction: creatinine clearance < 15 mL/min or glomerular filtration rate< 15 mL/min
9. uncontrolled infection
10. human immunodeficiency virus infection
11. active hepatitis b virus, hepatitis C virus infection and need antivirus treatment.
12. relapse of primary malignant hematological diseases, or graft rejection.
13. allergic history to Janus kinase inhibitors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: combination therapy; There is only 1 arm. Combination therapy arm includes ruxolitinib and methylprednisolone.; Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 1 week, then taper according to the clinical response.; Ruxolitinib oral tablet, 5~10mg bid orally, for at least 28 days.	Drug: Ruxolitinib Oral Tablet; Ruxolitinib Oral Tablet （Jakafi）, 5~10mg bid po for at least 28 days.; Other Names: Jakafi; Drug: Methylprednisolone; Methylprednisolone: 2mg/kg/d , iv or iv gtt, for at least 1 week, then taper accordingly.; Other Names: steroid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate	overall response rate of acute GVHD treatment, including complete response rate and partial response rate after combination therapy.	28 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to response	days from beginning to the first day of maximum response	28 days after treatment
reactivation rate of cytomegalovirus	reactivation rate of cytomegalovirus infection	100 days within transplant
1 year incidence of chronic GVHD	incidence of chronic GVHD 1 year after transplant	1 year within transplant

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Xianmin Song, M.D., Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): September 20, 2024
• Study Completion (Actual): September 20, 2024

Study Registration Dates

• First Submitted: October 8, 2018
• First Submitted That Met QC Criteria: October 8, 2018
• First Posted (Actual): October 10, 2018

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: September 27, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: SHSYXY-Ruxo-GVHD-2018001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes