Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Irwin Walker

ORCID ID

Contact details

1200 Main St. West
Hamilton
L9G 1K9
Canada
+1 905 521 2100 ext. 76384
walkeri@mcmaster.ca

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MCT-99786; CBMTG 0801

Study information

Scientific title

A randomised trial of thymoglobulin to prevent chronic graft versus host disease in patients undergoing haematopoietic progenitor cell transplantation (HPCT) from unrelated donors

Acronym

Study hypothesis

The addition of thymoglobulin to the preparative regimen will result in a decrease in the proportion of patients with chronic graft versus host disease (cGVHD), resulting in improved quality of life but without an increase in mortality, disease relapse or death due to infection.

Ethics approval

McMaster University-Hamilton Health Sciences Research Ethics Board approved on the 28th January 2010.

Study design

Phase III multicentre randomised clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Chronic graft versus host disease

Intervention

This is a randomised trial. Patients randomised to the thymoglobulin arm will receive thymoglobulin 0.5 mg/kg on Days -2 and -1 prior to HPCT, and then a dose of 2.0 mg/kg on Day 0 (for a total dose of 4.5 mg/kg [actual body weight]). Quality of life questionnaires will be administered at screening and again at 6, 12 and 24 months post-HPCT. Participants will be asked to complete a cGVHD Symptom Scale at 100 days post-HPCT and again at 6, 12 and 24 months post-HPCT (and also at the time of diagnosis of cGVHD). Participants will also be asked to complete questionnaires related to health care resource utilisation and personal costs at 6, 12 and 24 months post-HPCT as part of a health cost comparison between the two study arms.

The preparative regimen for the control arm will not include thymoglobulin. Participants will be asked to complete the same questionnaires as the participants in the thymoglobulin arm. In both arms, all treatment and follow-up will be according to standard institutional practice (except for the addition of the thymoglobulin to the preparative regimen in the thymoglobulin arm).

Intervention type

Drug

Phase

Phase III

Drug names

Thymoglobulin

Primary outcome measures

Freedom of cGVHD at 12 months from transplantation defined as withdrawal of all systemic immunosuppressive agents without resumption up to 12 months after transplantation.

Secondary outcome measures

1. Time to engraftment: complete blood count (CBC) measured daily until engraftment of platelets and neutrophils
2. Incidence of acute GVHD: participants will be assessed daily while in hospital and then according to local institutional practice until month 24
3. Incidence of cGVHD according to NIH Consensus criteria: measured at 100 days, 6 months, 12 months and 24 months using the "Chronic GVHD Assessment Form"
4. Incidence of cGVHD according to Sullivan Criteria: measured at day 100, months 6, 12 and 24 using the "Chronic GVHD Assessment Form"
5. Time to non-relapse mortality: time dependent variable
6. Time to all-cause mortality: time dependent variable
7. Time to relapse of leukaemia: measured according to local institutional practice at time there are signs/symptoms of relapse
8. Incidence of graft rejection or failure: CBC measured daily until engraftment of platelets and neutrophils
9. Incidence of serious infection: participants are assessed for signs of infection according to local institutional practice
10. Incidence of cytomegalovirus (CMV) activation: screening CMV is to occur according to local institutional practice
11. Quality of life: questionnaires collected at screening, 6, 12 and 24 months
12. Cost effectiveness: questionnaires collected at screening, 6, 12 and 24 months
13. Incidence of specific organ grades (National Institutes of Health [NIH]) of cGVHD: measured at 100 days, 6 months, 12 months and 24 months post-HPCT
14. Number of months on immunosuppression up to 12 months post-transplant: measured at 100 days, 6, 12 and 24 months post-transplant using the "Chronic GVHD Assessment Form"
15. Proportion of patients needing immunosuppression at 24 months: measured at 24 months post-HPCT using the "Chronic GVHD Assessment Form"
16. Doses of immunosuppressive drugs at 12 months: measured (assessed) at 12 months using the "Chronic GVHD Assessment Form"
17. Immunosuppressive therapy at time of diagnosis of cGVHD, prior to treatment of cGVHD: measured (assessed) at time of diagnosis of cGVHD. "Chronic GVHD Assessment Form" is to be completed at this time.

Overall trial start date

10/03/2010

Overall trial end date

01/12/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. The recipient is aged between 16 and 70 years, either sex
2. The recipient has an haematologic malignancy i.e. one of:
2.1. Acute leukaemia, myeloid, lymphoid, or biphenotypic, in 1st or 2nd remission or be in early relapse (no chemotherapy within three months and blasts less than 10% and with previous remission having been longer than 3 months)
2.2. Chronic myeloid leukaemia, in chronic or stable accelerated phase
2.3. Chronic lymphocytic leukaemia
2.4. Lymphoma
2.5. Myelodysplastic syndrome
2.6. Myeloproliferative disorder
3. The recipient will receive one of the specified preparative regimens
4. The recipient will receive either a bone marrow ("HPC, Marrow") or blood progenitor cell ("HPC, Apheresis") graft
5. 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
6. The recipient meets the transplant centre's criteria for unrelated donor allogeneic transplantation, either myeloablative or non-myeloablative (syn. RIC)
7. The recipient has good performance status (Karnofsky greater than or equal to 60%)
8. Recipient has given signed informed consent
9. For the questionnaire component only, be able to complete the questionnaires in English or with a validated translation

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

198

Participant exclusion criteria

1. The recipient is human immunodeficiency virus (HIV) antibody positive
2. The recipient has a hypersensitivity to rabbit proteins or thymoglobulin pharmaceutical excipients, glycine or mannitol
3. The recipient has an active infection (i.e. infection requiring oral or intravenous [IV] therapy)
4. The recipient (if female and of childbearing potential) is pregnant or breast-feeding at the time of enrolment
5. The recipient (if female and of childbearing potential) does not agree to use an adequage contraceptive method from the time of enrolment until a minimum of one year following transplant
6. The recipient (if male and fertile) does not agree to use an adequate contraceptive method from the time of enrolment until a minimum of one year following transplant
7. 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)

Recruitment start date

10/03/2010

Recruitment end date

01/12/2015

Locations

Countries of recruitment

Canada

Trial participating centre

1200 Main St. West
Hamilton
L9G 1K9
Canada

Sponsor information

Organisation

McMaster University (Canada)

Sponsor details

Faculty of Health Science
HSC 1B7
1200 Main Street
Hamilton
L8N 3Z5
Canada
+1 905 521 2100 ext. 74595
ciaramem@hhsc.ca

Sponsor type

University/education

Website

http://www.hamiltonhealthsciences.ca/body.cfm?id=1067

Funders

Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-99786)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Genzyme Corporation (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Editorial Notes