Thymoglobulin in Unrelated Hematopoietic Progenitor Cell Transplantation

Hematologic Malignancies Clinical Trial

Official title:

A Randomized Trial of Thymoglobulin to Prevent Chronic Graft Versus Host Disease in Patients Undergoing Hematopoietic Progenitor Cell Transplantation (HPCT) From Unrelated Donors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01217723
• Other study ID #: CBMTG 0801
• Status: Recruiting
• Phase: Phase 3
• First received: September 29, 2010
• Last updated: October 7, 2010
• Start date: April 2010
• Est. completion date: January 2014

Study information

• Verified date: September 2010
• Source: McMaster University
• Contact: Holly M Kerr, BA, BSN
• Phone: 604-875-4111
• Email: hkerr[@]bccancer.bc.ca
• Is FDA regulated: No
• Health authority: Canada: Health CanadaUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This is a randomized trial for patients undergoing hematopoietic progenitor cell transplantation (HPCT) from an unrelated donor. Approximately 50% of the patients enrolled will receive Thymoglobulin® as part of the preparative regimen prior to HPCT. The other 50% of the patients enrolled will receive a standard preparative regimen. Thymoglobulin is known to suppress the types of cells that can cause a transplant complication known as "chronic graft versus host disease (cGVHD)". The goal of this trial is to find out if adding Thymoglobulin to the preparative regimen will result in a decrease in cGVHD.

Description:

This study is a non-blinded, randomized, multicentre trial testing the effect of Thymoglobulin® vs. placebo on the primary outcome of cGVHD. Subjects will be children and adults having unrelated donor transplants.

Intervention: Infusion of Thymoglobulin® on three days prior to the transplant.

Hypothesis: The hypothesis is that the use of Thymoglobulin® in the experimental group will result in an absolute 20% increase in the number of patients free of cGVHD at 12 months, the time of peak incidence, from 20% in the control group to 40% in the experimental group.

Outcome Measures: The Primary Outcome Measure is freedom from cGVHD at 12 months from transplantation, defined as withdrawal of all systemic immunosuppressive agents and without resumption up to 12 months (a binary end-point, yes/no). Secondary outcome measures: Quality of Life, overall incidence of cGVHD (including untreated cases and resolved cases), the incidence of "extensive" cGVHD, time to non-relapse mortality, time to all-cause mortality, time to relapse of leukemia, graft rejection or failure (Yes vs. No), serious infection (Yes vs. No), CMV activation (Yes vs. No), organ-specific grading of chronic graft versus host disease, resumption of immunosuppressive agents after 12 months (Yes vs. No), doses of immunosuppressive drugs still required at 12 months, and incidence of acute graft versus host disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 198
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 70 Years

Eligibility

Inclusion Criteria:

• The recipient has a hematologic malignancy

• The recipient will receive one of the specified preparative regimens

• The recipient will receive either a bone marrow ("HPC, Marrow") or blood progenitor cell ("HPC, Apheresis") graft

• The recipient has an unrelated donor who with high resolution typing is either fully MHC matched at HLA-A, B, C and DRB1 with the recipient or is 1-antigen or 1-allele mismatched at A, B, C or DRB1 loci The recipient meets the transplant centre's criteria for unrelated donor allogeneic transplantation , either myeloablative or non-myeloablative (syn. RIC).

• The recipient has good performance status (Karnofsky =60%)

• Recipient has given signed informed consent For the questionnaire component only, be able to complete the questionnaires in English or with a validated translation (as posted on the project website)

Exclusion Criteria:

• The recipient is HIV antibody positive

• The recipient has a hypersensitivity to rabbit proteins or Thymoglobulin pharmaceutical excipients, glycine or mannitol

• The recipient has active or chronic infection (i.e. infection requiring oral or IV therapy)

• The recipient (if female and of childbearing potential) is pregnant or breast-feeding at the time of enrollment

• The recipient (if female and of childbearing potential) does not agree to use an adequate contraceptive method from the time of enrollment until a minimum of one year following transplant

• The recipient (if male and fertile) does not agree to use an adequate contraceptive method from the time of enrollment until a minimum of one year following transplant

• For the questionnaire component only, the recipient is unable to participate due to cognitive, linguistic or emotional difficulties (i.e. the recipient can participate in the main study but will be excluded from the questionnaire component

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hematologic Malignancies

Intervention

Biological:
• Anti-Thymocyte Globulin (Rabbit)
Thymoglobulin 0.5 mg/kg on Day -2 prior to the Transplant, 2.5 mg/kg on Day -1, and 2.5 mg/kg on the day of transplant.

Other:
• Patients will receive a standard preparative regimen (i.e. one that does not contain Thymoglobulin)
The standard preparative regimen can be myeloablative or reduced intensity.

Locations

Country	Name	City	State
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Juravinski Hospital & Cancer Centre	Hamilton	Ontario
Canada	Hopital de l'Enfant Jesus	Montreal	Quebec
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Royal Victoria Hospital	Montreal	Quebec
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	L'Hotel Dieu de Quebec	Quebec City	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba

Sponsors (4)

Lead Sponsor	Collaborator
McMaster University	Canadian Institutes of Health Research (CIHR), Genzyme, a Sanofi Company, The Canadian Blood and Marrow Transplant Group

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Freedom from Chronic GVHD	"Freedom from Chronic GVHD" is defined as withdrawal of all systemic immunosuppressive agents and without resumption up to 12 months (a binary endpoint, yes/no)	12 months post transplant	No
Secondary	Quality of Life	A series of questionnaires measured at the screening interval (up to 3 months prior to transplant), 6, 12 and 24 months post transplant.	Measured at Screening, Month 6, 12 and 24	No