Clinical trial NCT05021276: Basiliximab Combined With Ruxolitinib as Second-line Treatment of Grade 3-4 Steroid-resistant aGVHD
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Safety and Efficacy
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: Soochow Hopes Hematonosis Hospital
name: The Second People's Hospital of Huai'an
First posted: 2021-08-25
Enrollment: 50
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 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.

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.

Eligibility criteria: 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.

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: Time to response
timeFrame: through study completion(median 12 days according to previous study)
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
measure: incidence rate of secondary grade 3-4 liver aGVHD
timeFrame: through study completion, an average of 1 year
measure: incidence rated of chronic GVHD
timeFrame: through study completion, an average of 1 year
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: