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

NCT04688021 | Unknown Phase 2 DMC

• 1 other identifier: TZ-001
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Leukemia; Graft-versus-host-disease

Keywords

hematopoietic stem cell transplantation; graft-versus-host disease

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Cumulative incidence of engraftment

  100 days

• Cumulative incidence of infections

  2 years

• Overall survival (OS)

  2 years

• Progression-free survival (PFS)

  2 years

• Cumulative incidence of transplant-related nonrelapse mortality (NRM)

  2 years

Study Arms (1)

Tocilizumab cohort

EXPERIMENTAL

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; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Me-CCNU; Drug: Rabbit antithymocyte globulin; Drug: Tocilizumab; Procedure: Allogeneic HSCT; Drug: Cyclosporin A; Drug: Mycophenolate Mofetil; Drug: MTX

Interventions

Cytarabine DRUG

4 mg/m2/day administered IV day -10 through -9.

Tocilizumab cohort

Busulfan DRUG

3.2 mg/kg/day administered IV day -8 through -6.

Tocilizumab cohort

Cyclophosphamide DRUG

1.8 g/m2/day administered IV day -5 through -4.

Tocilizumab cohort

Me-CCNU DRUG

250mg/m2 once administered orally on day -3.

Tocilizumab cohort

Rabbit antithymocyte globulin DRUG

1.5mg/kg/day administered IV day -5 through -2.

Tocilizumab cohort

Tocilizumab DRUG

8mg/kg administered IV on day -1.

Tocilizumab cohort

Allogeneic HSCT PROCEDURE

Day 0

Tocilizumab cohort

Cyclosporin A DRUG

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.

Tocilizumab cohort

Mycophenolate Mofetil DRUG

500 mg/day administered intravenously from day -9, ended in complete withdrawal on day +100.

Tocilizumab cohort

MTX DRUG

15 mg/m2 administered intravenously on day +1, 10mg/m2 on day +3, +6, and +9.

Tocilizumab cohort

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yi Luo: lead

Study Sites (1)

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, China

RECRUITING

MeSH Terms

Conditions

Leukemia; Graft vs Host Disease

Interventions

Cytarabine; Busulfan; Cyclophosphamide; Semustine; thymoglobulin; tocilizumab; Cyclosporine; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Lomustine; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Yi Luo

  First Affiliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yi Luo, MD

CONTACT

86-13666609126; luoyijr@zju.edu.com

Lizhen Liu, MD

CONTACT

86-15858222740; lizhenliuzju@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: December 11, 2020
• First Posted: December 29, 2020
• Study Start: December 3, 2020
• Primary Completion: December 3, 2024
• Study Completion: December 31, 2024
• Last Updated: February 21, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)