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

February 19, 2023 updated by: Yi Luo

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

46

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Hangzhou, China
        • Recruiting
        • The First Affiliated Hospital, College of Medicine, Zhejiang University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tocilizumab cohort
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.
Drug: Cytarabine
4 mg/m2/day administered IV day -10 through -9.
Drug: Busulfan
3.2 mg/kg/day administered IV day -8 through -6.
Drug: Cyclophosphamide
1.8 g/m2/day administered IV day -5 through -4.
Drug: Me-CCNU
250mg/m2 once administered orally on day -3.
Drug: Rabbit antithymocyte globulin
1.5mg/kg/day administered IV day -5 through -2.
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.
Drug: Mycophenolate Mofetil
500 mg/day administered intravenously from day -9, ended in complete withdrawal on day +100.
Drug: MTX
15 mg/m2 administered intravenously on day +1, 10mg/m2 on day +3, +6, and +9.
Drug: Tocilizumab
8mg/kg administered IV on day -1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative incidence of grade II-IV acute graft-versus-host disease
Time Frame: 100 days
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
Cumulative incidence of non grade II-IV acute graft-versus-host disease survival
Time Frame: 100 days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative incidence of transplant-related nonrelapse mortality (NRM)
Time Frame: 2 years
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
Overall survival (OS)
Time Frame: 2 years
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
Progression-free survival (PFS)
Time Frame: 2 years
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
Cumulative incidence of disease relapse or progression
Time Frame: 2 years
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
Cumulative incidence of engraftment
Time Frame: 100 days
All patients will be tracked from Day 0 to date of myeloid and platelet engraftments, respectively.
100 days
Cumulative incidence of infections
Time Frame: 2 years
All patients will be tracked from Day 0 to date of infection diagnosis as proved by relevant standard diagnostic criteria.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yi Luo

Investigators

  • Principal Investigator: Yi Luo, First Affiliated Hospital of Zhejiang University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 3, 2020

Primary Completion (Anticipated)

December 3, 2024

Study Completion (Anticipated)

December 31, 2024

Study Registration Dates

First Submitted

December 11, 2020

First Submitted That Met QC Criteria

December 25, 2020

First Posted (Actual)

December 29, 2020

Study Record Updates

Last Update Posted (Estimate)

February 21, 2023

Last Update Submitted That Met QC Criteria

February 19, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TZ-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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