Clinical trial NCT06066840: Vedolizumab, Anti-CD25 Antibody, Rapid Reduction of Glucocorticoids for SR-aGVHD With Gastrointestinal Involvement
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Safety and Efficacy
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital with Nanjing Medical University
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Affiliated Hospital of Nantong University
First posted: 2023-10-04
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: overall response rate at day 28
timeFrame: day 28
Secondary outcomes:
measure: ORR at d14/d56
timeFrame: day 14, day 56
measure: Duration of response
timeFrame: through study completion, an average of 1year
measure: OS
timeFrame: through study completion, an average of 1year
measure: EFS
timeFrame: through study completion, an average of 1year
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Xuefeng He, doctor
role: PRINCIPAL_INVESTIGATOR
References: