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

Hematopoietic Stem Cell Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01883180
• Other study ID #: NFEC-201304-K1
• Status: Completed
• Phase: Phase 4
• First received: June 14, 2013
• Last updated: April 21, 2018
• Start date: June 2013
• Est. completion date: January 2018

Study information

• Verified date: January 2018
• Source: Nanfang Hospital of Southern Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 412
• Est. completion date: January 2018
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Antithymocyte Globulin
• Graft vs Host Disease
• Hematopoietic Stem Cell Transplantation
• Viral Infection
• Virus Diseases

Intervention

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.

Locations

Country	Name	City	State
China	Department of Hematology,Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong

Sponsors (7)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University	First Affiliated Hospital of Guangxi Medical University, Fujian Medical University Union Hospital, Guangzhou General Hospital of Guangzhou Military Command, Peking University People's Hospital, Southern Medical University, China, Xiangya Hospital

Country where clinical trial is conducted

China, 

References & Publications (2)

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. — View Citation

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. Epub 2003 Apr 10. — View Citation

Outcome

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