Thymoglobulin in Unrelated Hematopoietic Progenitor Cell Transplantation

Condition(s) targeted: Hematologic Malignancies

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

Phase: Phase 3

Status: Recruiting

Sponsored by: McMaster University

Official(s) and/or principal investigator(s):
Irwin Walker, MD, Study Chair, Affiliation: McMaster University, Faculty of Health Sciences

Overall contact:
Holly M Kerr, BA, BSN, Phone: 604-875-4111, Ext: 63196, Email: hkerr@bccancer.bc.ca

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.

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

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

Primary outcome: Freedom from Chronic GVHD

Secondary outcome: Quality of Life

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.

Minimum age: 16 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

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

Holly M Kerr, BA, BSN, Phone: 604-875-4111, Ext: 63196, Email: hkerr@bccancer.bc.ca

Vancouver General Hospital, Vancouver, British Columbia V5Z 1M9, Canada; Recruiting
Holly M Kerr, BA, BSN, Phone: 604-875-4111, Ext: 63196, Email: hkerr@bccancer.bc.ca
Catherine L Singh, Phone: 604-875-4111, Ext: 69013, Email: csingh@bccancer.bc.ca
Thomas Nevill, MD, Principal Investigator

CancerCare Manitoba, Winnipeg, Manitoba R3E 0V9, Canada; Recruiting
David Szwajcer, MD, Phone: 204-787-4179, Email: david.szwajcer@cancercare.mb.ca

Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia B3H 2YA, Canada; Recruiting
Stephen Couban, MD, Phone: 902-473-7006, Email: stephen.couban@cdha.nshealth.ca

Juravinski Hospital & Cancer Centre, Hamilton, Ontario L8V 1C3, Canada; Recruiting
Irwin Walker, MD, Phone: 905-521-2100, Ext: 76384, Email: walkeri@mcmaster.ca

Ottawa Hospital, Ottawa, Ontario K1H 8L6, Canada; Not yet recruiting
Jason Tay, MD, Phone: 613-737-8899, Ext: 73034, Email: jtay@toh.on.ca

Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada; Not yet recruiting
John Kuruvilla, MD, Phone: 416-946-4466, Email: john.kuruvilla@uhn.on.ca

Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada; Not yet recruiting
Gizelle Popradi, MD, Phone: 514-934-1934, Ext: 31558, Email: gizelle.propardi@muhc.mcgill.ca

Hopital Maisonneuve-Rosemont, Montreal, Quebec H1T 2M4, Canada; Recruiting
Jean Roy, MD, Phone: 514-252-3400, Ext: 3404, Email: jroy.hmr@ssss.gouv.qc.ca

Hopital de l'Enfant Jesus, Montreal, Quebec G1J 1Z4, Canada; Not yet recruiting
Genevieve Gallagher, MD, Phone: 418-649-5727, Email: genevieve.gallagher.cha@ssss.gouv.qc.ca

L'Hotel Dieu de Quebec, Quebec City, Quebec G1R 2J6, Canada; Not yet recruiting
Felix Couture, MD, Email: felixcou@videotron.ca

Starting date: April 2010
Last updated: October 7, 2010