A Single-arm Trial of Prophylactic Tocilizumab for Acute GVHD Prevention After Haploidentical HSCT.

Leukemia Clinical Trial

Official title:

A Single-arm, Single-center Trial of Prophylactic Tocilizumab for Acute GVHD Prevention After Haploidentical HSCT.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04688021
• Other study ID #: TZ-001
• Status: Recruiting
• Phase: Phase 2
• Start date: December 3, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2023
• Source: First Affiliated Hospital of Zhejiang University
• Contact: Yi Luo, MD
• Phone: 86-13666609126
• Email: luoyijr[@]zju.edu.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A single-arm trial using Tocilizumab for acute GVHD prophylaxis after haploidentical HSCT.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: December 31, 2024
• Est. primary completion date: December 3, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 60 Years

Eligibility

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 (ß-chorionic gonadotropin+) or breast feeding
• Refusal to sign the informed consent

Related Conditions & MeSH terms

• Graft vs Host Disease
• Graft-versus-host-disease
• Leukemia

Intervention

Drug:
• Cytarabine
4 mg/m2/day administered IV day -10 through -9.
• Busulfan
3.2 mg/kg/day administered IV day -8 through -6.
• Cyclophosphamide
1.8 g/m2/day administered IV day -5 through -4.
• Me-CCNU
250mg/m2 once administered orally on day -3.
• Rabbit antithymocyte globulin
1.5mg/kg/day administered IV day -5 through -2.
• Tocilizumab
8mg/kg administered IV on day -1.

Procedure:
• Allogeneic HSCT
Day 0

Drug:
• Cyclosporin A
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.
• Mycophenolate Mofetil
500 mg/day administered intravenously from day -9, ended in complete withdrawal on day +100.
• MTX
15 mg/m2 administered intravenously on day +1, 10mg/m2 on day +3, +6, and +9.

Locations

Country	Name	City	State
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou

Sponsors (1)

Lead Sponsor	Collaborator
Yi Luo

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	100 days
Primary	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.	100 days
Secondary	Cumulative incidence of engraftment	All patients will be tracked from Day 0 to date of myeloid and platelet engraftments, respectively.	100 days
Secondary	Cumulative incidence of infections	All patients will be tracked from Day 0 to date of infection diagnosis as proved by relevant standard diagnostic criteria.	2 years
Secondary	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.	2 years
Secondary	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.	2 years
Secondary	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.	2 years
Secondary	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.	2 years