SHR0302 and Steroid as First Line Therapy for Chronic GVHD

SHR0302 and Prednisone as First Line Therapy for Chronic Graft Versus Host Disease Following Allogeneic Stem Cell Transplantation

The purpose of this study is to evaluate the efficacy of SHR0302 in combination with Prednisone as first line therapy in patients with moderate to severe chronic graft-versus-host disease (GVHD).

Study Overview

• Status: Recruiting
• Conditions: Chronic GVHD
• Intervention / Treatment: Drug: SHR0302; Drug: Prednisone

Detailed Description

Treatment: Once patients are diagnosed with chronic GVHD, the combination therapy should be initiated as soon as possible. 1. Prednisone: 1mg/kg/d po. Taper steroid every two weeks according to patient's response. 2. SHR0302 QD po. for at least 28 days. Indication for stopping SHR0302 treatment: 1. No response after SHR0302 treatment for 12 weeks. 2. Develop life-threatening complication. 3. ANC<0.5×10e9/L or PLT< 30×10e9/L.

• Study Type: Interventional
• Enrollment (Estimated): 73
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Huiying Qiu, M.D.; Phone Number: 86-21-37798987; Email: qiuhy5@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Recruiting
      • Xianmin Song
      • Contact: Xianmin Song, Doctor; Phone Number: 3932 86-21-63240090; Email: shongxm@sjtu.edu.cn
    • Shanghai, Shanghai, China, 200080
      • Recruiting
      • Shanghai General Hospital
      • Contact: Xianmin Song, MD; Phone Number: 3175 +86 21 63240090
      • Principal Investigator: Xianmin Song, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ≥ 18 years old and ≤ 70 years old, male or female;
• Patients receiving allogeneic peripheral blood stem cell transplantation for hematological diseases;
• The primary hematological malignancies are completely relieved and are expected to be stable for at least 3 months;
• Chronic GVHD that was first attacked after transplantation and at least 100 days after transplantation, reached a moderate or severe level by NIH classification;
• There was no previous systemic treatment (including in vitro illumination [ECP]);
• The patient may be receiving other immunosuppressive agents to prevent or treat acute GVHD, but if the subject receives prednisone to prevent or treat acute GVHD, it must be <0.5 mg/kg/d or equivalent dose of other glucocorticoids;
• The chronic GVHD that has started hormone therapy does not exceed 72 hours;
• Karnofsky score > 60 points;
• Patients must be able to understand and are willing to participate in the study and sign an informed consent form.

Exclusion Criteria:

• Can not tolerate prednisone dose 1mg / kg / d or equivalent dose of other glucocorticoids for the treatment of cGVHD;
• Receive any systemic treatment of cGVHD, except for corticosteroids that treat cGVHD within 72 hours prior to the signing of informed consent;
• Patients with GVHD overlap syndrome (NIH criteria);
• Treatment of acute GVHD has received other Jak inhibitors such as ruxolitinib;
• Pregnant or lactating women;
• The patient is judged by the investigator to have complications that may cause other risks;
• The patient is receiving other study medications;
• Patient blood routine: ANC <1.0 × 109 / L or PLT < 50 × 109 / L;
• Non-GVHD-related liver damage: the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio is more than 3 times normal or the direct bilirubin normal value is more than 3 times;
• Renal dysfunction: endogenous creatinine clearance (Ccr) < 50mL/min or normal serum creatinine 1.5 times or more, regardless of hemodialysis treatment;
• Uncontrolled infections: hemodynamic instability associated with infection, or new signs or signs of infection, or new infections in imaging, persistent fever without symptoms or signs and cannot be ruled out Infected person
• People living with HIV;
• Active hepatitis B (HBV), active hepatitis C (HCV) requires antiviral therapy; patients with HBV activation risk refer to patients with hepatitis B surface antigen-positive or core antibody-positive patients who are not treated with anti-HBV;
• The patient's primary malignant disease recurs and the graft is rejected;
• Those who are allergic to known JAK inhibitors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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; Experimental: combination therapy There is only 1 arm. Combination therapy arm includes SHR0302 and Prednisone Prednisone 1mg/kg/d po，At the same time give SHR0302 QDpo；	Drug: SHR0302; SHR0302 po QD; Drug: Prednisone; Prednisone 1mg/kg/d po

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of SHR0302 and prednisone	The severity of adverse events is determined according to the CTCAE V5.0 criteria.	After the first dose of SHR0302 or prednisone until 30 days after the last dose of SHR0302 or prednisone.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) at week 4	Response rate at week 4 (the proportion of responders [CR or PR]) as defined by the NIH Consensus Development Project (2014)	Within 4 weeks
Overall response rate (ORR) at week 24	Response rate at week 24 (the proportion of responders [CR or PR]) as defined by the NIH Consensus Development Project (2014)	Within 24 weeks

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): April 2, 2020
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: October 25, 2019
• First Submitted That Met QC Criteria: October 30, 2019
• First Posted (Actual): October 31, 2019

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: SHSYXY-cGVHD-2019002

Drug and device information, study documents

• 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.: Yes