Thymoglobulin in Unrelated Hematopoietic Progenitor Cell Transplantation

Phase 3

Interventions: Biological: Anti-Thymocyte Globulin (Rabbit)
Other: Patients will receive a standard preparative regimen (i.e. one that does not contain Thymoglobulin)

Brief 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.

Detailed 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 & 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

Arm && Interventions

Group	Intervention	Description
Thymoglobulin	Anti-Thymocyte Globulin (Rabbit)	Thymoglobulin will be administered on Days -2, -1 prior to the transplant and on the day of transplant.
No Thymoglobulin	Patients will receive a standard preparative regimen (i.e. one that does not contain Thymoglobulin)	Patients will receive a standard preparative regimen. (i.e. one that does not normally contain Thymoglobulin.)

Primary Outcome Measures

Name	Time	Method
Freedom from Chronic GVHD	12 months post transplant	"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)

Secondary Outcome Measures

Name	Time	Method
Quality of Life	Measured at Screening, Month 6, 12 and 24	A series of questionnaires measured at the screening interval (up to 3 months prior to transplant), 6, 12 and 24 months post transplant.

Locations (10): Royal Victoria Hospital
🇨🇦
Montreal, Quebec, Canada
Hopital Maisonneuve-Rosemont
🇨🇦
Montreal, Quebec, Canada
Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada
L'Hotel Dieu de Quebec
🇨🇦
Quebec City, Quebec, Canada
Ottawa Hospital
🇨🇦
Ottawa, Ontario, Canada
CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
Juravinski Hospital & Cancer Centre
🇨🇦
Hamilton, Ontario, Canada
Hopital de l'Enfant Jesus
🇨🇦
Montreal, Quebec, Canada
Vancouver General Hospital
🇨🇦
Vancouver, British Columbia, Canada
Queen Elizabeth II Health Sciences Centre
🇨🇦
Halifax, Nova Scotia, Canada