Vedolizumab, Anti-CD25 Antibody, Rapid Reduction of Glucocorticoids for SR-aGVHD With Gastrointestinal Involvement

Safety and Efficacy Clinical Trial

Official title:

Vedolizumab, Anti-CD25 Antibody Combined With Rapid Reduction of Glucocorticoids as Treatment of Grade 3-4 Steroid-resistant Acute Graft-versus-host Disease With Lower Gastrointestinal Involvement

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06066840
• Other study ID #: GVHD002
• Status: Recruiting
• Phase: Phase 4
• Start date: August 1, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2023
• Source: The First Affiliated Hospital of Soochow University
• Contact: Xuefeng He, doctor
• Phone: 86-18914031640
• Email: hexuefeng[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Acute graft-versus-host disease (aGVHD) is the most common life-threatening complication of allogeneic hematopoietic stem cell transplantation. The investigators try to observe the efficacy and safety of application of vedolizumab, anti-CD25 monoclonal antibody and rapid reduction of glucocorticoids in the treatment of grade 3-4 steroid-refractory aGVHD(SR-aGVHD) with lower gastrointestinal involvement.

Description:

Sample size: According to Simon optimal two-stage design, P0=60%, P1=80%, α=0.05, β=0.2, a sample size of 45 was chosen.

Objects: Adults ages 18-65 diagnosed with grade 3-4 SR-aGVHD with lower gastrointestinal involvement.

Design

Participants with grade 3-4 SR-aGVHD with lower gastrointestinal involvement(progression after 3 days or lack of improvement after 5 days of 1-2 mg/kg/d systemic steroids) receive combined therapy of vedolizumab and anti-CD25 monoclonal antibody, with methylprednisolone terminated in 7-10 days.

Vedolizumab is given 300mg, day 1/15/43, and then once every 8 weeks until gastrointestinal GVHD reaches grade 1 (1 episodes for minimum).

Basiliximab is given 20mg twice a week for week 1, and then once a week until GVHD of the participants reaches grade 2(3 episodes for minimum). If basiliximab is not available, it can be replaced by recombinant humanized anti-CD25 monoclonal antibody injection, 50mg once with the same frequency.

Methylprednisolone is reduced to 1mg/kg/d at day 1 and is aborted in 7-10 days. If chronic GVHD or overlap syndrome is considered later during treatment, steroids (ie. methylprednisolone 0.5mg/kg/d) can be administered again.

Intravenous cyclosporine or tacrolimus is given and plasma concentration is monitored in a safe and effective range.

Best supportive treatment is given, including broad-spectrum anti-infection, nutrition support, and blood transfusion.

The investigators access the efficacy and safety of second-line therapy once a week from day 14 until complete remission is received. Then the investigators access the hematological disease status, aGVHD, cGVHD, infection state once a month.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 31, 2025
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of grade 3-4(according to MAGIC criteria) steroid-resistant acute graft-versus-host disease(progression after 3 days or lack of improvement after 5 days of systemic 1.5-2 mg/kg steroids) with gastrointestinal involvement.

• Age 18-65.

• ECOG score=3.

• Must be able to understand and willing to participate in the study and sign the informed consent.

Exclusion Criteria:

• Refractory/secondary graft-versus-host disease.

• Severe complications such as myocardial infarction, chronic cardiac insufficiency,

• hepatic failure, renal insufficiency, etc.

• Clinically uncontrolled active infections.

• Other Malignant tumors with progression.

• Heart failure: EF<30%, NYHA=grade III.

• Pregnant or lactating women.

• Expected survival <60 days.

• Undergoing other drug clinical trials.

Related Conditions & MeSH terms

• Safety and Efficacy

Intervention

Drug:
• Basiliximab
Basiliximab is a second-line treatment for steroid-resistant acute graft-versus-host disease.
• Vedolizumab
Vedolizumab is a second-line treatment for steroid-resistant acute graft-versus-host disease.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (4)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University	Affiliated Hospital of Nantong University, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, The First Affiliated Hospital with Nanjing Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall response rate at day 28	The primary endpoint is the overall response rate (ORR) at day 28 defined as proportion of patients demonstrating partial (PR) or complete response (CR) without requirement for additional systemic immunosuppressive therapy (IST) at day 28 after second-line treatment initiates.	day 28
Secondary	ORR at d14/d56	overall response rate at day 14/56	day 14, day 56
Secondary	Duration of response	Duration of response, assessed for responders only by calculating the time from first response to the date of first observation of aGvHD relapse/progression or the date of additional IST for GvHD.	through study completion, an average of 1year
Secondary	OS	Overall survival (OS) defined as time from the day treatment initiates to the date of death from any cause.	through study completion, an average of 1year
Secondary	EFS	Event-free survival (EFS) defined as the time from the day treatment initiates to the date of recurrence of underlying hematologic disease, graft failure or death due to any cause.	through study completion, an average of 1year