Thymoglobulin to prevent chronic graft versus host disease in hematopoietic progenitor cell transplantation patients

ISRCTN	ISRCTN29899028
DOI	https://doi.org/10.1186/ISRCTN29899028
ClinicalTrials.gov (NCT)	NCT01217723
Protocol serial number	MCT-99786; CBMTG 0801
Sponsor	McMaster University (Canada)
Funders	Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-99786), Genzyme

Submission date: 18/02/2010
Registration date: 23/02/2010
Last edited: 21/01/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Injury, Occupational Diseases, Poisoning

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Irwin Walker
Scientific

1200 Main St. West
Hamilton
L9G 1K9
Canada

Phone	+1 (0)905 521 2100 ext. 76384
Email	walkeri@mcmaster.ca

Study information

Primary study design	Interventional
Study design	Phase III multicentre randomised clinical trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
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
Study objectives	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(s)	McMaster University-Hamilton Health Sciences Research Ethics Board, 28/01/2010
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Thymoglobulin
Primary outcome measure(s)	Freedom of cGVHD at 12 months from transplantation defined as withdrawal of all systemic immunosuppressive agents without resumption up to 12 months after transplantation.
Key secondary outcome measure(s)	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.
Completion date	01/12/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	198
Total final enrolment	203
Key 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
Key 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)
Date of first enrolment	10/03/2010
Date of final enrolment	01/12/2015

Locations

Countries of recruitment

Canada

Study participating centre

1200 Main St. West

Hamilton
L9G 1K9
Canada

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/02/2016		Yes	No
Results article	results	01/02/2020	21/01/2020	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

21/01/2020: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
3. ClinicalTrials.gov number added.