Clinical trial NCT04146207: SHR0302 and Steroid As First Line Therapy for Chronic GVHD
Official title: SHR0302 and Prednisone As First Line Therapy for Chronic Graft Versus Host Disease Following Allogeneic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Chronic GVHD
Lead sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2019-10-31
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability of SHR0302 and prednisone
timeFrame: After the first dose of SHR0302 or prednisone until 30 days after the last dose of SHR0302 or prednisone.
Secondary outcomes:
measure: Overall response rate (ORR) at week 4
timeFrame: Within 4 weeks
measure: Overall response rate (ORR) at week 24
timeFrame: Within 24 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Shanghai
country: China
facility: Xianmin Song
state: Shanghai
Study officials:
affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
name: Xianmin Song, M.D.
role: PRINCIPAL_INVESTIGATOR
References: