Efficacy and Safety of Anti-CD25 rhMAb in the Treatment of Steroid-Refractory cGVHD

Study on the Efficacy and Safety of Anti-CD25 rhMAb in the Treatment of Steroid-Refractory Chronic Graft-Versus-Host Disease (cGVHD) of the Liver Following Allogeneic Hematopoietic Stem Cell Transplantatio

The study plan aims to include patients who have been diagnosed with steroid-refractory chronic GVHD in the liver following allogeneic hematopoietic stem cell transplantation. After obtaining informed consent, the patients will be randomly assigned to either the Anti-CD25 rhMAb treatment group or the traditional treatment group. The objective is to assess the effectiveness and safety of Anti-CD25 rhMAb in the treatment of severe chronic GVHD affecting the liver.

Study Overview

• Status: Not yet recruiting
• Conditions: cGVHD
• Intervention / Treatment: Drug: anti-CD25 rhMAb; Drug: Prednisone; Drug: Ruxolitinib; Drug: Cyclosporine

• Study Type: Interventional
• Enrollment (Estimated): 118
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 16 and 65 years
2. Received allogeneic hematopoietic stem cell transplantation
3. Developed chronic GVHD in the liver after transplantation
4. Ineffective prednisone treatment prior to screening
5. Received ≤4 lines of systemic therapy prior to screening
6. After informed consent, the patient agreed to receive anti-CD25 rhMAb treatment

Exclusion Criteria:

1. Elevation of bilirubin, ALT, or alkaline phosphatase due to reasons other than chronic GVHD
2. No prior treatment with prednisone
3. Overlap syndrome
4. Uncontrolled active infection
5. Organ failure
6. Early progression or recurrence of hematologic diseases
7. Allergy to anti-CD25 rhMAb
8. Received other interleukin-2 receptor monoclonal antibody treatment due to various reasons within one month after transplantation
9. Participated in other clinical studies within one month

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anti-CD25 rhMAb + traditional therapy	Drug: anti-CD25 rhMAb; 1 mg/kg/day administered IV day 1, 4, and 8, then weekly for 6 doses. For patients achieving partial remission, an extra dose of Anti-CD25 rhMAb can be given on days 39 and 49.; Drug: Prednisone; Maintain pre-screening dose; Drug: Ruxolitinib; 10mg, BID PO; Drug: Cyclosporine; 1.25mg/kg, BID PO/IV, target:150-250ng/ml
Placebo Comparator: traditional therapy	Drug: Prednisone; Maintain pre-screening dose; Drug: Ruxolitinib; 10mg, BID PO; Drug: Cyclosporine; 1.25mg/kg, BID PO/IV, target:150-250ng/ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate (ORR)	ORR is defined as the percentage of complete response (CR) and partial response (PR).	56 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
duration of response（DOR）	DOR is defined as the duration calculated from the time of achieving PR or CR until the progression of GVHD, the addition of other systemic immunosuppressive therapy, or death.	1 year
patient-reported outcomes (PRO)	Based on the Lee Chronic GVHD Symptom Scale.	1 year
disease-free survival (DFS)	DFS is defined as the duration of survival after treatment in which the original hematologic disease is in a state of complete remission.	1 year
failure-free survival (FFS)	Events that are considered as failures include the onset of new chronic GVHD, relapse, and death.	1 year
non-relapse mortality (NRM)	NRM is defined as death due to reasons other than progression/relapse of hematologic disease.	1 year
overall survival （OS）	OS is defined as the time from treatment until death from any cause or the last follow-up.	1 year
adverse drug reactions (ADR)	The occurrence of various organ toxicities related to treatment that emerge following treatment.	1 year

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: April 12, 2024
• First Posted (Estimated): April 15, 2024

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Prednisone; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 2024PHD002-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Our plan is to disseminate the findings of this trial via peer-reviewed articles.

Drug and device information, study documents

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