Thymoglobulin in Unrelated Hematopoietic Progenitor Cell Transplantation

NCT ID: NCT01217723

Last Updated: 2010-10-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

198 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-04-30

Study Completion Date

2014-01-31

Brief Summary

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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

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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.

Conditions

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Hematologic Malignancies

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Thymoglobulin

Thymoglobulin will be administered on Days -2, -1 prior to the transplant and on the day of transplant.

Group Type EXPERIMENTAL

Anti-Thymocyte Globulin (Rabbit)

Intervention Type BIOLOGICAL

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.

No Thymoglobulin

Patients will receive a standard preparative regimen. (i.e. one that does not normally contain Thymoglobulin.)

Group Type OTHER

Patients will receive a standard preparative regimen (i.e. one that does not contain Thymoglobulin)

Intervention Type OTHER

The standard preparative regimen can be myeloablative or reduced intensity.

Interventions

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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.

Intervention Type BIOLOGICAL

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.

Intervention Type OTHER

Other Intervention Names

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Thymoglobulin ATGr rabbit

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role collaborator

The Canadian Blood and Marrow Transplant Group

NETWORK

Sponsor Role collaborator

McMaster University

OTHER

Sponsor Role lead

Responsible Party

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McMaster University

Principal Investigators

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Irwin Walker, MD

Role: STUDY_CHAIR

McMaster University, Faculty of Health Sciences

Locations

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Vancouver General Hospital

Vancouver, British Columbia, Canada

Site Status RECRUITING

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status RECRUITING

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Site Status RECRUITING

Juravinski Hospital & Cancer Centre

Hamilton, Ontario, Canada

Site Status RECRUITING

Ottawa Hospital

Ottawa, Ontario, Canada

Site Status NOT_YET_RECRUITING

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status NOT_YET_RECRUITING

Hopital de l'Enfant Jesus

Montreal, Quebec, Canada

Site Status NOT_YET_RECRUITING

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Site Status RECRUITING

Royal Victoria Hospital

Montreal, Quebec, Canada

Site Status NOT_YET_RECRUITING

L'Hotel Dieu de Quebec

Québec, Quebec, Canada

Site Status NOT_YET_RECRUITING

Countries

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Canada

Central Contacts

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Holly M Kerr, BA, BSN

Role: CONTACT

604-875-4111 ext. 63196

Catherine L Singh

Role: CONTACT

604-875-411 ext. 69013

Facility Contacts

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Holly M Kerr, BA, BSN

Role: primary

604-875-4111 ext. 63196

Catherine L Singh

Role: backup

604-875-4111 ext. 69013

David Szwajcer, MD

Role: primary

204-787-4179

Stephen Couban, MD

Role: primary

902-473-7006

Irwin Walker, MD

Role: primary

905-521-2100 ext. 76384

Jason Tay, MD

Role: primary

613-737-8899 ext. 73034

John Kuruvilla, MD

Role: primary

416-946-4466

Genevieve Gallagher, MD

Role: primary

418-649-5727

Jean Roy, MD

Role: primary

514-252-3400 ext. 3404

Gizelle Popradi, MD

Role: primary

514-934-1934 ext. 31558

Felix Couture, MD

Role: primary

References

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Chakupurakal G, Freudenberger P, Skoetz N, Ahr H, Theurich S. Polyclonal anti-thymocyte globulins for the prophylaxis of graft-versus-host disease after allogeneic stem cell or bone marrow transplantation in adults. Cochrane Database Syst Rev. 2023 Jun 21;6(6):CD009159. doi: 10.1002/14651858.CD009159.pub3.

Reference Type DERIVED
PMID: 37341189 (View on PubMed)

Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, Gallagher G, Kerr H, Kuruvilla J, Lee SJ, Moore J, Nevill T, Popradi G, Roy J, Schultz KR, Szwajcer D, Toze C, Foley R; Cell Therapy Transplant Canada. Addition of anti-thymocyte globulin to standard graft-versus-host disease prophylaxis versus standard treatment alone in patients with haematological malignancies undergoing transplantation from unrelated donors: final analysis of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2020 Feb;7(2):e100-e111. doi: 10.1016/S2352-3026(19)30220-0. Epub 2020 Jan 17.

Reference Type DERIVED
PMID: 31958417 (View on PubMed)

Naeije L, Kariminia A, Abdossamadi S, Azadpour S, Subrt P, Kuzeljevic B, Irvine MA, Walker I, Schultz KR. Anti-Thymocyte Globulin Prophylaxis Induces a Decrease in Naive Th Cells to Inhibit the Onset of Chronic Graft-versus-Host Disease: Results from the Canadian Bone Marrow Transplant Group (CBMTG) 0801 Study. Biol Blood Marrow Transplant. 2020 Mar;26(3):438-444. doi: 10.1016/j.bbmt.2019.11.015. Epub 2019 Nov 19.

Reference Type DERIVED
PMID: 31756535 (View on PubMed)

Other Identifiers

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CBMTG 0801

Identifier Type: -

Identifier Source: org_study_id