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

Sponsor
The First Affiliated Hospital of Soochow University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05021276
Collaborator
Soochow Hopes Hematonosis Hospital (Other), The Second People's Hospital of Huai'an (Other)
50
1
1
24
2.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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 Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 15, 2020
Anticipated Primary Completion Date :
Jul 31, 2022
Anticipated Study Completion Date :
Dec 15, 2022

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. overall response rate at day 28 [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.

    Secondary Outcome Measures

    1. ORR at d14/d56 [day 14, day 56]

      overall response rate at day 14/56

    2. Time to response [through study completion(median 12 days according to previous study)]

      Time to response, defined as time from the day treatment initiates to the date of first documentation PR or CR.

    3. Duration of response [through study completion, an average of 1year]

      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.

    4. OS [through study completion, an average of 1year]

      Overall survival (OS) defined as time from the day treatment initiates to the date of death from any cause.

    5. EFS [through study completion, an average of 1year]

      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.

    6. incidence rate of secondary grade 3-4 liver aGVHD [through study completion, an average of 1 year]

      incidence rate of secondary grade 3-4 liver aGVHD

    7. incidence rated of chronic GVHD [through study completion, an average of 1 year]

      incidence rated of chronic GVHD

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 scoreā‰¤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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The First Affiliated Hospital of Soochow University Suzhou Jiangsu China 215006

    Sponsors and Collaborators

    • The First Affiliated Hospital of Soochow University
    • Soochow Hopes Hematonosis Hospital
    • The Second People's Hospital of Huai'an

    Investigators

    • Principal Investigator: Xuefeng He, doctor, The First Affiliated Hospital of Soochow University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Xuefeng He, chief physician, The First Affiliated Hospital of Soochow University
    ClinicalTrials.gov Identifier:
    NCT05021276
    Other Study ID Numbers:
    • GVHD-001
    First Posted:
    Aug 25, 2021
    Last Update Posted:
    Aug 25, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 25, 2021