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

NCT ID: NCT06066840

Last Updated: 2023-10-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-01
• Study Completion Date: 2025-12-31

Brief 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.

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.

Conditions

Safety and Efficacy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

vedolizumab+basiliximab

Patients with steroid-refractory aGVHD with gastrointestinal involvement receive combined therapy of vedolizumab and basiliximab.

Group Type: EXPERIMENTAL

Basiliximab

Intervention Type: DRUG

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

Vedolizumab

Intervention Type: DRUG

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

Interventions

Basiliximab

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

Intervention Type: DRUG

Vedolizumab

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

Intervention Type: DRUG

Other Intervention Names

anti-CD25 monoclonal antibody; anti-α4β7 monoclonal antibody

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: collaborator

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

OTHER

Sponsor Role: collaborator

Affiliated Hospital of Nantong University

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xuefeng He, doctor

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Soochow University

Locations

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xuefeng He, doctor

Role: CONTACT

hexuefeng@suda.edu.cn

86-18914031640

Fei Zhou, doctor

Role: CONTACT

zhoufei@suda.edu.cn

86-15051425673

Facility Contacts

Xuefeng He, doctor

Role: primary

hexuefeng@suda.edu.cn

86-18914031640

Fei Zhou, doctor

Role: backup

zhoufei@suda.edu.cn

86-15051425673

Other Identifiers

GVHD002

Identifier Type: -

Identifier Source: org_study_id