Basiliximab Combined With Ruxolitinib as Second-line Treatment of Grade 3-4 Steroid-resistant aGVHD

A Prospective Multicenter, Single-arm Clinical Study of Anti-CD25 Monoclonal Antibody Combined With Ruxolitinib in the Treatment of Grade 3-4 Steroid-resistant Acute Graft-versus-host Disease

Acute graft-versus-host disease (aGVHD) is the most common life-threatening complication of allogeneic hematopoietic stem cell transplantation. The recognized first-line treatment for grade 3-4 aGVHD is systemic glucocorticoid. However, there is no recognized second-line treatment for grade 3-4 steroid-resistant aGVHD (SR-aGVHD). The investigators try to observe the efficacy and safety of early application of anti-CD25 monoclonal antibody(basiliximab) combined with ruxotilinib in the treatment of severe SR-aGVHD.

Study Overview

• Status: Recruiting
• Conditions: Safety and Efficacy
• Intervention / Treatment: Drug: Ruxolitinib

Detailed Description

Adults ages 18-65 with grade 3-4 SR-aGVHD

Design

Participants with grade 3-4 steroid-refractory acute GVHD (progression after 3 days or lack of improvement after 5 days of 1.5-2 mg/kg/d systemic steroids) receive combined therapy of basiliximab and ruxolitinib.

Basiliximab is given 20mg twice a week for week 1, and then once a week until GVHD of the participants reaches grade 1(3 episodes for minimum).

Ruxolitinib is given 5mg twice a day for one day and then escalates to 10mg twice a day if the participant is not administered with triazole antifungal agent.

The drug dose will be adjusted according to participants' clinical manifestations, blood cell count, infection status and so on.

For participants with lower gastrointestinal GVHD, 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 (Anticipated): 50
• 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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of primary 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).
• 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.
• Ecg: QT interval > 450 ms.
• Allergic to arsenic agent.
• 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: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ruxolitinib+basiliximab; Patients with grade 3-4 steroid-refractory aGVHD receive combined therapy of basiliximab and ruxolitinib.	Drug: Ruxolitinib; Ruxolitinib and basiliximab are both second-line treatment for grade 3-4 steroid-resistant acute graft-versus-host disease.; Other Names: basiliximab

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
Time to response	Time to response, defined as time from the day treatment initiates to the date of first documentation PR or CR.	through study completion(median 12 days according to previous study)
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
incidence rate of secondary grade 3-4 liver aGVHD	incidence rate of secondary grade 3-4 liver aGVHD	through study completion, an average of 1 year
incidence rated of chronic GVHD	incidence rated of chronic GVHD	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: The Second People's Hospital of Huai'an; Soochow Hopes Hematonosis Hospital
• Investigators: Principal Investigator: Xuefeng He, doctor, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 15, 2020
• Primary Completion (ANTICIPATED): July 31, 2022
• Study Completion (ANTICIPATED): December 15, 2022

Study Registration Dates

• First Submitted: August 17, 2021
• First Submitted That Met QC Criteria: August 23, 2021
• First Posted (ACTUAL): August 25, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 23, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Basiliximab
• Other Study ID Numbers: GVHD-001

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