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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Safety and Efficacy
• Intervention / Treatment: Drug: Basiliximab; Drug: Vedolizumab

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xuefeng He, doctor; Phone Number: 86-18914031640; Email: hexuefeng@suda.edu.cn
• Study Contact Backup: Name: Fei Zhou, doctor; Phone Number: 86-15051425673; Email: zhoufei@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Xuefeng He, doctor; Phone Number: 86-18914031640; Email: hexuefeng@suda.edu.cn
      • Contact: Fei Zhou, doctor; Phone Number: 86-15051425673; Email: zhoufei@suda.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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: vedolizumab+basiliximab; Patients with steroid-refractory aGVHD with gastrointestinal involvement receive combined therapy of vedolizumab and basiliximab.	Drug: Basiliximab; Basiliximab is a second-line treatment for steroid-resistant acute graft-versus-host disease.; Other Names: anti-CD25 monoclonal antibody; Drug: Vedolizumab; Vedolizumab is a second-line treatment for steroid-resistant acute graft-versus-host disease.; Other Names: anti-α4β7 monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR at d14/d56	overall response rate at day 14/56	day 14, day 56
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
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
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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; Affiliated Hospital of Nantong University
• Investigators: Principal Investigator: Xuefeng He, doctor, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 31, 2023
• First Submitted That Met QC Criteria: September 27, 2023
• First Posted (Actual): October 4, 2023

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Antibodies; Immunoglobulins; Vedolizumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Basiliximab
• Other Study ID Numbers: GVHD002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No