Back to resultsA Single-arm Trial of Prophylactic Tocilizumab for Acute GVHD Prevention After Haploidentical HSCT.
Primary Purpose
Leukemia, Graft-versus-host-disease
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Cytarabine
Busulfan
Cyclophosphamide
Me-CCNU
Rabbit antithymocyte globulin
Tocilizumab
Allogeneic HSCT
Cyclosporin A
Mycophenolate Mofetil
MTX
Sponsored by
About this trial
This is an interventional prevention trial for Leukemia focused on measuring hematopoietic stem cell transplantation, graft-versus-host disease
Eligibility Criteria
Inclusion Criteria:
- Patients with hematological malignancies in complete remission (CR) who are eligible and planned for haploidentical HSCT. The donor specific antibody is negative
- Patient age 16-60 years
- Mother donor, or female donor (age >50) for female-male transplant
- Eastern Cooperative Oncology Group (ECOG) performance status < 2
- Creatinine clearance rate > 60 mL/min (estimate by Cockcroft-Gault Equation)
- alanine transaminase (ALT) and aspartate aminotransferase (AST)≤ 2.5×upper limit of normal (ULN), and total bilirubin ≤ 1.5×ULN （upper limit of normal, ULN）
- Left ventricular ejection fraction (LVEF) ≥50% as measured by echocardiography
- Acceptation to sign the informed consent
Exclusion Criteria:
- History of previous HSCT
- Present active infection (including bacterial, virus or fungal)
- History of Tocilizumab infection
- History of inflammatory bowel disease
- History of demyelinating disease
- Patients who are HIV-positive, or with uncontrolled chronic hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV) infections
- Women who are pregnant (β-chorionic gonadotropin+) or breast feeding
- Refusal to sign the informed consent
Sites / Locations
- The First Affiliated Hospital, College of Medicine, Zhejiang UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tocilizumab cohort
Arm Description
Each patient receives Tocilizumab (8 mg/kg, i.v.) on day -1 added to conventional acute GVHD prophylaxis regimen (CsA+MTX+low-dose MMF+ATG) of haploidentical HSCT.
Outcomes
Primary Outcome Measures
Cumulative incidence of grade II-IV acute graft-versus-host disease
Date of symptom onset, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II-IV acute graft-versus-host disease (aGVHD) will be recorded. The aGVHD score of each affected organ will be recorded.
Cumulative incidence of non grade II-IV acute graft-versus-host disease survival
All patients will be tracked from Day 0 to date of grade II-IV acute graft-versus-host disease (aGVHD) onset. Patients who did not present grade II-IV aGVHD or died will be censored at the last date they were assessed and deemed free of grade II-IV aGVHD.
Secondary Outcome Measures
Cumulative incidence of engraftment
All patients will be tracked from Day 0 to date of myeloid and platelet engraftments, respectively.
Cumulative incidence of infections
All patients will be tracked from Day 0 to date of infection diagnosis as proved by relevant standard diagnostic criteria.
Overall survival (OS)
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Progression-free survival (PFS)
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Cumulative incidence of transplant-related nonrelapse mortality (NRM)
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Cumulative incidence of disease relapse or progression
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04688021
Brief Title
A Single-arm Trial of Prophylactic Tocilizumab for Acute GVHD Prevention After Haploidentical HSCT.
Official Title
A Single-arm, Single-center Trial of Prophylactic Tocilizumab for Acute GVHD Prevention After Haploidentical HSCT.
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 3, 2020 (Actual)
Primary Completion Date
December 3, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Yi Luo
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A single-arm trial using Tocilizumab for acute GVHD prophylaxis after haploidentical HSCT.
Detailed Description
This study will enroll haploidentical HSCT patients with high risk for acute GVHD. Tocilizumab (8mg/kg) will be added to the conventional acute GVHD prophylaxis regime (CsA+Methotrexate(MTX)+low dose mycophenolate mofetil(MMF)+ATG) on day -1 of transplant. The previous patients will be used as control.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Graft-versus-host-disease
Keywords
hematopoietic stem cell transplantation, graft-versus-host disease
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
46 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tocilizumab cohort
Arm Type
Experimental
Arm Description
Each patient receives Tocilizumab (8 mg/kg, i.v.) on day -1 added to conventional acute GVHD prophylaxis regimen (CsA+MTX+low-dose MMF+ATG) of haploidentical HSCT.
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
4 mg/m2/day administered IV day -10 through -9.
Intervention Type
Drug
Intervention Name(s)
Busulfan
Intervention Description
3.2 mg/kg/day administered IV day -8 through -6.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
1.8 g/m2/day administered IV day -5 through -4.
Intervention Type
Drug
Intervention Name(s)
Me-CCNU
Intervention Description
250mg/m2 once administered orally on day -3.
Intervention Type
Drug
Intervention Name(s)
Rabbit antithymocyte globulin
Intervention Description
1.5mg/kg/day administered IV day -5 through -2.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Intervention Description
8mg/kg administered IV on day -1.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic HSCT
Intervention Description
Day 0
Intervention Type
Drug
Intervention Name(s)
Cyclosporin A
Intervention Description
2.5 mg/kg/day administered intravenously from day -7, target: 200-300ng/mL. Usually tapered during the second month, and ended in complete withdrawal during the ninth month after transplantation.
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Intervention Description
500 mg/day administered intravenously from day -9, ended in complete withdrawal on day +100.
Intervention Type
Drug
Intervention Name(s)
MTX
Intervention Description
15 mg/m2 administered intravenously on day +1, 10mg/m2 on day +3, +6, and +9.
Primary Outcome Measure Information:
Title
Cumulative incidence of grade II-IV acute graft-versus-host disease
Description
Date of symptom onset, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II-IV acute graft-versus-host disease (aGVHD) will be recorded. The aGVHD score of each affected organ will be recorded.
Time Frame
100 days
Title
Cumulative incidence of non grade II-IV acute graft-versus-host disease survival
Description
All patients will be tracked from Day 0 to date of grade II-IV acute graft-versus-host disease (aGVHD) onset. Patients who did not present grade II-IV aGVHD or died will be censored at the last date they were assessed and deemed free of grade II-IV aGVHD.
Time Frame
100 days
Secondary Outcome Measure Information:
Title
Cumulative incidence of engraftment
Description
All patients will be tracked from Day 0 to date of myeloid and platelet engraftments, respectively.
Time Frame
100 days
Title
Cumulative incidence of infections
Description
All patients will be tracked from Day 0 to date of infection diagnosis as proved by relevant standard diagnostic criteria.
Time Frame
2 years
Title
Overall survival (OS)
Description
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Time Frame
2 years
Title
Progression-free survival (PFS)
Description
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Time Frame
2 years
Title
Cumulative incidence of transplant-related nonrelapse mortality (NRM)
Description
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Time Frame
2 years
Title
Cumulative incidence of disease relapse or progression
Description
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with hematological malignancies in complete remission (CR) who are eligible and planned for haploidentical HSCT. The donor specific antibody is negative
Patient age 16-60 years
Mother donor, or female donor (age >50) for female-male transplant
Eastern Cooperative Oncology Group (ECOG) performance status < 2
Creatinine clearance rate > 60 mL/min (estimate by Cockcroft-Gault Equation)
alanine transaminase (ALT) and aspartate aminotransferase (AST)≤ 2.5×upper limit of normal (ULN), and total bilirubin ≤ 1.5×ULN （upper limit of normal, ULN）
Left ventricular ejection fraction (LVEF) ≥50% as measured by echocardiography
Acceptation to sign the informed consent
Exclusion Criteria:
History of previous HSCT
Present active infection (including bacterial, virus or fungal)
History of Tocilizumab infection
History of inflammatory bowel disease
History of demyelinating disease
Patients who are HIV-positive, or with uncontrolled chronic hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV) infections
Women who are pregnant (β-chorionic gonadotropin+) or breast feeding
Refusal to sign the informed consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yi Luo, MD
Phone
86-13666609126
Email
luoyijr@zju.edu.com
First Name & Middle Initial & Last Name or Official Title & Degree
Lizhen Liu, MD
Phone
86-15858222740
Email
lizhenliuzju@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yi Luo
Organizational Affiliation
First Affiliated Hospital of Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital, College of Medicine, Zhejiang University
City
Hangzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yi Luo, MD
Phone
86-13666609126
Email
luoyijr@zju.edu.com
First Name & Middle Initial & Last Name & Degree
Lizhen Liu, MD
Phone
86-15858222740
Email
lizhenliuzju@126.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Single-arm Trial of Prophylactic Tocilizumab for Acute GVHD Prevention After Haploidentical HSCT.
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