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

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: Leukemia; Graft-versus-host-disease
• Intervention / Treatment: Drug: Cytarabine; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Me-CCNU; Drug: Rabbit antithymocyte globulin; Procedure: Allogeneic HSCT; Drug: Cyclosporin A; Drug: Mycophenolate Mofetil; Drug: MTX; Drug: Tocilizumab

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

• Study Contact: Name: Yi Luo, MD; Phone Number: 86-13666609126; Email: luoyijr@zju.edu.com
• Study Contact Backup: Name: Lizhen Liu, MD; Phone Number: 86-15858222740; Email: lizhenliuzju@126.com

Study Locations

• China
  • Hangzhou, China
    • Recruiting
    • The First Affiliated Hospital, College of Medicine, Zhejiang University
    • Contact: Yi Luo, MD; Phone Number: 86-13666609126; Email: luoyijr@zju.edu.com
    • Contact: Lizhen Liu, MD; Phone Number: 86-15858222740; Email: lizhenliuzju@126.com

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

1

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	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	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)	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)	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)	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	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	All patients will be tracked from Day 0 to date of myeloid and platelet engraftments, respectively.	100 days
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

Collaborators and Investigators

• Sponsor: Yi Luo
• Investigators: Principal Investigator: Yi Luo, First affiliated Hospital of Zhejiang University

Study record dates

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: hematopoietic stem cell transplantation; graft-versus-host disease
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Cyclophosphamide; Cytarabine; Mycophenolic Acid; Busulfan; Thymoglobulin; Antilymphocyte Serum; Cyclosporine; Cyclosporins
• 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