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

Safety and Efficacy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05021276
• Other study ID #: GVHD-001
• Status: Recruiting
• Phase: Phase 4
• Start date: December 15, 2020
• Est. completion date: December 15, 2022

Study information

• Verified date: August 2021
• Source: The First Affiliated Hospital of Soochow University
• Contact: Xuefeng He, doctor
• Phone: 86-18914031640
• Email: hexuefeng[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 15, 2022
• Est. primary completion date: July 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Safety and Efficacy

Intervention

Drug:
• Ruxolitinib
Ruxolitinib and basiliximab are both second-line treatment for grade 3-4 steroid-resistant acute graft-versus-host disease.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (3)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University	Huai'an Second People's Hospital, Soochow Hopes Hematonosis Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	ORR at d14/d56	overall response rate at day 14/56	day 14, day 56
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	incidence rated of chronic GVHD	incidence rated of chronic GVHD	through study completion, an average of 1 year