ATG in Haploidentical HSCT for Acute Graft-versus-host Disease Prophylaxis

Dose Study of Antithymocyteglobulin in Haploidentical Hematopoietic Stem Cell Transplantation for Acute Graft-versus-host Disease Prophylaxis

The purpose of this study is to compare the incidences of GVHD and viral infections in haploidentical hematopoietic stem cell transplant recipients receiving different dose of antithymocyte globulin (ATG) for acute graft-versus-host disease(aGVHD) prophylaxis. Our first objective was to investigate the optimal dose of ATG for aGVHD and second object was to evaluate the effect of different dose of ATG on post-transplant viral infection.

Study Overview

• Status: Completed
• Conditions: Hematopoietic Stem Cell Transplantation; Viral Infection; Antithymocyte Globulin
• Intervention / Treatment: Drug: ATG

Detailed Description

Allogeneic hematopoietic stem cell transplantation (allo-HSCT)is the only therapeutic option for many hematological malignancies. Unfortunately, about 75% of patients who require allo-HSCT lack human leukocyte antigen (HLA)-matched donors. The alternative is hematopoietic stem cells from an HLA-mismatched family donor. However, this strategy, which is called haploidentical HSCT, may be associated with high risk of early death and severe GVHD.

Opportunistic infections are common complications after allo-HSCT. Due to the absence of effective preventive and therapeutic drugs for most viruses, viral infections has become one of the most important causes of death. The immunosuppression regimen including ATG has been shown effective to prevent severe GVHD in haploidentical HSCT. But this strategy delays immune reconstitution, and therefore increase the risk of viral infection.

The optimal dose of the different ATG preparations with respect to prevention of GvHD is not fully understood today. The total doses between 6 mg/kg to 15 mg/kg are effective for prevention of GVHD, but the dose above 10 mg/kg may increase the development of viral infection.

In this trial, we will focus on the incidence of aGVHD and viral infections in patients treated with 7.5mg/kg or 10mg/kg of ATG. The incidence of GVHD and viral infections will be compared between different dose arms.

• Study Type: Interventional
• Enrollment (Actual): 412
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Department of Hematology,Nanfang Hospital, Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A patient age of 14-65 years
• Haploidentical hematopoietic stem cell transplant recipient
• Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

• Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
• Patients with any conditions not suitable for the trial (investigators' decision)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ATG 7.5mg/kg; ATG 7.5mg/kg group refers to treatment with ATG in the total dose of 7.5mg/kg.	Drug: ATG; ATG will be intravenously infused via a central venous catheter in 3 or 4 days, from day -4 or -3 until day -1. The other conditioning drugs administered before transplantation include cytosine arabinoside (Ara-C), busulfan (Bu),cyclophosphamide (Cy), Semustine(Me-CCNU), and ATG. All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF), and short-term methotrexate for aGVHD prevention.
EXPERIMENTAL: ATG 10mg/kg; ATG 10mg/kg group refers to treatment with ATG in the total dose of 10mg/kg.	Drug: ATG; ATG will be intravenously infused via a central venous catheter in 3 or 4 days, from day -4 or -3 until day -1. The other conditioning drugs administered before transplantation include cytosine arabinoside (Ara-C), busulfan (Bu),cyclophosphamide (Cy), Semustine(Me-CCNU), and ATG. All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF), and short-term methotrexate for aGVHD prevention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Epstein-Barr virus(EBV) viremia	Incidence of EBV viremia within 1 year	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute GVHD	Acute GVHD was graded according to standard criteria.	100 days
Incidence of EBV-associated diseases	the Incidence of EBV-associated end-organ diseases	2 years
Immune reconstitution	Immune reconstitution is performed every 3 months after transplantation.	1 year
Survival	Survival includes overall and disease-free survival within 2 years after transplantation.	3 years
Incidence of chronic GVHD	Chronic GVHD was assessed in patients alive after day 100.	2 years
Incidence of cytomegalovirus(CMV) viremia	Incidence of CMV viremia within 1 year	1 year
Incidence of CMV-associated diseases	the Incidence of CMV-associated end-organ diseases	2 years

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Peking University People's Hospital; Fujian Medical University Union Hospital; Guangzhou General Hospital of Guangzhou Military Command; Southern Medical University, China; First Affiliated Hospital of Guangxi Medical University; Xiangya Hospital

Publications and helpful links

General Publications

• Ottinger HD, Ferencik S, Beelen DW, Lindemann M, Peceny R, Elmaagacli AH, Husing J, Grosse-Wilde H. Hematopoietic stem cell transplantation: contrasting the outcome of transplantations from HLA-identical siblings, partially HLA-mismatched related donors, and HLA-matched unrelated donors. Blood. 2003 Aug 1;102(3):1131-7. doi: 10.1182/blood-2002-09-2866. Epub 2003 Apr 10.
• Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Barbanti M, Sacchi N, Van Lint MT, Bosi A. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood. 2001 Nov 15;98(10):2942-7. doi: 10.1182/blood.v98.10.2942.
• Fan M, Wang Y, Lin R, Lin T, Huang F, Fan Z, Xu Y, Yang T, Xu N, Shi P, Nie D, Lin D, Jiang Z, Wang S, Sun J, Huang X, Liu Q, Xuan L. Haploidentical transplantation has a superior graft-versus-leukemia effect than HLA-matched sibling transplantation for Ph- high-risk B-cell acute lymphoblastic leukemia. Chin Med J (Engl). 2022 Apr 20;135(8):930-939. doi: 10.1097/CM9.0000000000001852.
• Yu S, Huang F, Fan Z, Xuan L, Nie D, Xu Y, Yang T, Wang S, Jiang Z, Xu N, Lin R, Ye J, Lin D, Sun J, Huang X, Wang Y, Liu Q. Haploidentical versus HLA-matched sibling transplantation for refractory acute leukemia undergoing sequential intensified conditioning followed by DLI: an analysis from two prospective data. J Hematol Oncol. 2020 Mar 12;13(1):18. doi: 10.1186/s13045-020-00859-5.
• Lin R, Wang Y, Huang F, Fan Z, Zhang S, Yang T, Xu Y, Xu N, Xuan L, Ye J, Sun J, Huang X, Liu Q. Two dose levels of rabbit antithymocyte globulin as graft-versus-host disease prophylaxis in haploidentical stem cell transplantation: a multicenter randomized study. BMC Med. 2019 Aug 12;17(1):156. doi: 10.1186/s12916-019-1393-7.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ACTUAL): September 1, 2017
• Study Completion (ACTUAL): January 1, 2018

Study Registration Dates

• First Submitted: June 14, 2013
• First Submitted That Met QC Criteria: June 19, 2013
• First Posted (ESTIMATE): June 21, 2013

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2018
• Last Update Submitted That Met QC Criteria: April 21, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: viral infection; Antithymocyte globulin; haploidentical hematopoietic Stem Cell Transplantation
• Additional Relevant MeSH Terms: Infections; Immune System Diseases; Virus Diseases; Graft vs Host Disease
• Other Study ID Numbers: NFEC-201304-K1