Graft-versus-host-diseasePhase 2ATG2017NCT03456817
HIgh Dose Thymoglobulin Instead of Cyclosporine With a Low Dose of Thymoglobulin for GVHD Prophylaxis
A Phase 2 study testing Treatment Arm - high dose ATG in people with Graft-versus-host-disease and Relapse, run by AHS Cancer Control Alberta at 1 site in Canada.
Trial summary
The purpose of this study is to find out whether compared to our standard low dose ATG with CSA, the high dose ATG with low-dose CSA minimizes the chances of relapse and chronic GVHD, without increasing the chances of other transplant complications. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft-versus-host-disease, Relapse
- What is being tested?
- Treatment Arm - high dose ATG
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteCanada
- Study dates
- 1 Jul 2020to 31 May 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- First allogeneic HCT, performed for a hematologic malignancy, using filgrastim-mobilized peripheral blood stem cells (PBSC).
- Conditioning with fludarabine 50 mg/m2 daily on day -6 to -2, busulfan approximately 3.2 mg/kg daily on day -5 to -2 with PK adjustment (target AUC of 3750 uM*min/L) and total body irradiation (TBI) 2 Gy x 2 given typically on day -1 and/or day 0 (before graft infusion), ie, our standard myeloablative conditioning.79 Dose and schedule adjustments per Investigator discretion are permitted.
- Planned GVHD prophylaxis with our standard of low-dose ATG (4.5 mg/kg) + MTX + high-dose CSA.
- HLA matched sibling donor, or ≥7/8 HLA allele-matched unrelated donor (maximum 1 allele mismatch at HLA-A, B, C, or DRB1).
- Age >17 years.
Who cannot join
- Nonmyeloablative conditioning.
- Cord blood or marrow graft.
- Myelofibrosis being the primary indication for HCT.
- Previous autologous or allogeneic HCT.
- Total Bilirubin >1.5-fold above upper normal limit (UNL), ALT >2.0-fold above UNL, or alkaline phosphatase >2.5-fold above UNL.
- HIV positive by a serologic test that includes detection of both antibody and antigen)
Show all 14Show fewer
- Increased risk of tuberculosis, defined as patient requiring an anti-tuberculosis drug peritransplant. All patients with a history of tuberculosis (active or latent) or contact with a person with active tuberculosis will be evaluated by an infectious disease specialist to determine whether treatment or prophylaxis of tuberculosis with an anti-tuberculosis drug peritransplant is needed. The infectious disease specialist will order tests (eg, Mantoux tuberculin skin test or interferon gamma release test) as needed to arrive at the decision on whether an anti-tuberculosis drug peritransplant is needed.
- High risk of cytomegalovirus (CMV) disease or recurrent CMViremia based on donor negative AND recipient positive CMV serostatus.2 If recipient serostatus was determined since the presentation of his/her hematologic malignancy more than once and the results are discrepant, the determination performed >4 weeks after a transfusion of platelets or plasma (or before transfusions of platelets or plasma were initiated) is considered valid. If unclear, the CMV serostatus determination will be at the discretion of the treating Investigator
- High risk of PTLD based on donor positive AND recipient negative Epstein-Barr virus (EBV) serostatus (EBNA1 or VCA IgG)80
- Hypersensitivity to rabbit blood protein, Thymoglobulin or a Thymoglobulin excipient.
- Severe obesity, defined as body mass index ≥40 kg/m2.81 The reason is that obese patients are at risk of achieving a high ATG area under the time vs concentration curve (AUC).82 This could lead to substantial toxicity (e.g., death due to an infection) when using the studied high dose (10 mg/kg) of ATG.
- Contraindication to methotrexate:
- Hypersensitivity to methotrexate or to any ingredient in the formulation or component of the container.
- Females of childbearing potential who are pregnant, breastfeeding or unwilling to use adequate contraception from the time of enrolment until at least day 100 posttransplant.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Tom Baker Cancer Centre/Arthur J.E. Child Comprehensive Cancer Centre
Calgary, Alberta
About this study
Official title: A Phase 2, Open-label Study to Evaluate Graft-vs-host Disease Prophylaxis With High Dose Thymoglobulin, Methotrexate, and Low-dose Cyclosporine in Comparison to Historical/Concurrent Controls Who Received Low Dose Thymoglobulin, Methotrexate, and High-dose Cyclosporine
The purpose of this study is to find out whether compared to our standard low dose ATG with CSA, the high dose ATG with low-dose CSA minimizes the chances of relapse and chronic GVHD, without increasing the chances of other transplant complications.
Read the detailed description
There are a number of complications of allogeneic hematopoietic cell transplantation.
The main complications are:
- Relapse (leukemia or leukemia-like disease returning). This usually leads to death.
- Acute graft-versus-host disease (GVHD). This may lead to death.
- Chronic GVHD. This may lead to poor quality of life long-term.
This study is being done to minimize the chances of patients getting relapse and chronic GVHD, without increasing the chances of getting acute GVHD.
At this time, the standard of care approach to treat this condition would be with:
- Low dose thymoglobulin (ATG), given on Day -2, -1 and 0.
- Cyclosporin (CSA), given from Day -1 through to Day 84.
- Methotrexate, given on Days 1, 3, 6 and 11
CSA reduces the chances of getting acute GVHD, but it does not reduce the chances of getting chronic GVHD and increases the chances of getting relapse. ATG reduces both acute and chronic GVHD, and does not increase relapse.
In this study, high dose ATG will be given on days -4, -3, -2, -1 and 0 (instead of only on days -2, -1 and 0), CSA will be given only from day 21 through 84 (instead of from day -1 through 84), and the routine dose of methotrexate (unchanged) will be given. We think that this may lead to better outcomes.
Patients will be followed per standard practice of the Alberta Blood and Marrow Transplant Program for the development of acute and chronic GVHD, and for relapse.
Patients will also be asked to complete a quality of life questionnaire 2 years after the transplant to assess how their treatment and illness affects their quality of life.
- Conditions
- Graft-versus-host-disease, Relapse
- Being tested
- Treatment Arm - high dose ATG, Control Arm - standard of care
- Medical subject headings
- Graft vs Host Disease, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment Arm - high dose ATGDrug
Patients agreeing to high dose ATG will be treated with 2 mg/kg daily on days -4 to 0. On days -4, -3 \& -2, ATG will be infused after fludarabine \& busulfan infusion. ATG will be infused over a minimum of 6 hrs on day -4 \& over at least 4 hrs on days -3, -2, -1 \& 0. Dose is based on actual body wt, \& rounded to nearest vial-Thymoglobulin is supplied in 25 mg vials, except if rounding would result in >5% difference from calculated dose. Foothills Medical Center Unit 57 standard practice followed for ATG infusion. ATG premeds include methylprednisolone, diphenhydramine, and an antipyretic. Meperidine 25-50 mg IVPB every 4 hours will be given as needed for rigors. MTX is given 15 mg/m2 IV on day +1 \& 10 mg/m2 on days +3, +6 \& +11 posttransplant. First dose of methotrexate is given on day +1, at least 24 hrs following end of infusion of stem cell product.
Control Arm - standard of careDrug
The historical controls will have received and the concurrent controls will receive our standard GVHD prophylaxis, ie, ATG 4.5 mg/kg i.v. (0.5 mg/kg on day -2, 2.0 mg/kg on day -1 and 2.0 mg/kg on day 0), MTX (15 mg/m2 i.v. on day 1 and 10 mg/m2 i.v. on days 3, 6 and 11) and CSA (2.5 mg/kg twice a day i.v. starting from day -1, adjusting dose to target trough plasma CSA levels of 200-400 microg/L, switching to oral formulation before discharge from peritransplant hospitalization, targeting the trough plasma levels of 200-400 microg/L until day 56, and tapering to zero between day 56 and 84).
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm - High dose ATG, Low dose CSA | Experimental | High dose ATG will be infused on days -4, -3, -2, -1 and 0. Before each infusion of ATG (thymoglobulin), patient will receive medications preventing side effects from the ATG, including diphenhydramine (Benadryl), an antipyretic (ibuprofen or acetaminophen) and methylprednisolone (Solumedrol). The high dose ATG will be given into patient's vein via central venous catheter. Each infusion of ATG will take 4-8 hours. CSA (cyclosporine A) will be given from day 21. Standard dose methotrexate will be given. Receives: Drug: Treatment Arm - high dose ATG |
| Control Arm - Standard of care | Other | Low dose ATG (thymoglobulin) will be infused on days -2, -1 and 0, and CSA (cyclosporine A) will be given from day -1 through day 84. Standard dose methotrexate will also be given. Receives: Drug: Control Arm - standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
moderate/severe chronic GVHD- and relapse-free survival (cGFRS) at 2 years post transplant
cGRFS will be compared between the study patients and the historical/concurrent controls using a Cox proportional hazards model to determine if administering high dose ATG + MTX and low dose CSA will be associated with improved cGRFS compared to historical/concurrent controls (4.5 mg/kg ATG + MTX + CSA).
Measured: 2 years
Secondary outcomes (1)
quality of life
each scale (domain) of the short form-36 (SF36) questionnaire will be compared between the high dose ATG group and the control group using Mann-Whitney-Wilcoxon signed rank test to determine if quality of life (QOL) at 2 years posttransplant will be better in the high dose ATG patients compared to the controls (due to the reduction of cGVHD).
Measured: approximately 2 years (21 to 27 months) post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2018
- Study start1 Jul 2020
- Primary completion31 May 2025
- Study completion31 May 2025
Why it stopped: Slow patient accrual and appearance of a toxicity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft-versus-host-diseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- AHS Cancer Control Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jan Storek, MD, Principal investigator, Tom Baker Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03456817
- Sponsor's protocol ID
- ATG2017
- Acronym
- ATG2017
- Status last verified
- Jul 2025
- First submitted
- 1 Mar 2018
- Last updated
- 18 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-label Study to Evaluate Graft-vs-host Disease Prophylaxis With High Dose Thymoglobulin, Methotrexate, and Low-dose Cyclosporine in Comparison to Historical/Concurrent Controls Who Received Low Dose Thymoglobulin, Methotrexate, and High-dose Cyclosporine
- ClinicalTrials.gov ID
- NCT03456817
- Acronym / sponsor ID
- ATG2017 / ATG2017
- Conditions
- Graft-versus-host-disease, Relapse
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow patient accrual and appearance of a toxicity
- Enrolment
- 68 participants (actual)
- Lead sponsor
- AHS Cancer Control AlbertaUniversity, hospital or other
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 31 May 2025 (actual)
- Study completion
- 31 May 2025 (actual)
- First posted
- 7 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out whether compared to our standard low dose ATG with CSA, the high dose ATG with low-dose CSA minimizes the chances of relapse and chronic GVHD, without increasing the chances of other transplant complications.
Detailed description
There are a number of complications of allogeneic hematopoietic cell transplantation.
The main complications are:
- Relapse (leukemia or leukemia-like disease returning). This usually leads to death.
- Acute graft-versus-host disease (GVHD). This may lead to death.
- Chronic GVHD. This may lead to poor quality of life long-term.
This study is being done to minimize the chances of patients getting relapse and chronic GVHD, without increasing the chances of getting acute GVHD.
At this time, the standard of care approach to treat this condition would be with:
- Low dose thymoglobulin (ATG), given on Day -2, -1 and 0.
- Cyclosporin (CSA), given from Day -1 through to Day 84.
- Methotrexate, given on Days 1, 3, 6 and 11
CSA reduces the chances of getting acute GVHD, but it does not reduce the chances of getting chronic GVHD and increases the chances of getting relapse. ATG reduces both acute and chronic GVHD, and does not increase relapse.
In this study, high dose ATG will be given on days -4, -3, -2, -1 and 0 (instead of only on days -2, -1 and 0), CSA will be given only from day 21 through 84 (instead of from day -1 through 84), and the routine dose of methotrexate (unchanged) will be given. We think that this may lead to better outcomes.
Patients will be followed per standard practice of the Alberta Blood and Marrow Transplant Program for the development of acute and chronic GVHD, and for relapse.
Patients will also be asked to complete a quality of life questionnaire 2 years after the transplant to assess how their treatment and illness affects their quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm - High dose ATG, Low dose CSA | Experimental | Drug: Treatment Arm - high dose ATGHigh dose ATG will be infused on days -4, -3, -2, -1 and 0. Before each infusion of ATG (thymoglobulin), patient will receive medications preventing side effects from the ATG, including diphenhydramine (Benadryl), an antipyretic (ibuprofen or acetaminophen) and methylprednisolone (Solumedrol). The high dose ATG will be given into patient's vein via central venous catheter. Each infusion of ATG will take 4-8 hours. CSA (cyclosporine A) will be given from day 21. Standard dose methotrexate will be given. |
| Control Arm - Standard of care | Other | Drug: Control Arm - standard of careLow dose ATG (thymoglobulin) will be infused on days -2, -1 and 0, and CSA (cyclosporine A) will be given from day -1 through day 84. Standard dose methotrexate will also be given. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- First allogeneic HCT, performed for a hematologic malignancy, using filgrastim-mobilized peripheral blood stem cells (PBSC).
- Conditioning with fludarabine 50 mg/m2 daily on day -6 to -2, busulfan approximately 3.2 mg/kg daily on day -5 to -2 with PK adjustment (target AUC of 3750 uM*min/L) and total body irradiation (TBI) 2 Gy x 2 given typically on day -1 and/or day 0 (before graft infusion), ie, our standard myeloablative conditioning.79 Dose and schedule adjustments per Investigator discretion are permitted.
- Planned GVHD prophylaxis with our standard of low-dose ATG (4.5 mg/kg) + MTX + high-dose CSA.
- HLA matched sibling donor, or ≥7/8 HLA allele-matched unrelated donor (maximum 1 allele mismatch at HLA-A, B, C, or DRB1).
- Age >17 years.
Key exclusion criteria (14 listed)
- Nonmyeloablative conditioning.
- Cord blood or marrow graft.
- Myelofibrosis being the primary indication for HCT.
- Previous autologous or allogeneic HCT.
- Total Bilirubin >1.5-fold above upper normal limit (UNL), ALT >2.0-fold above UNL, or alkaline phosphatase >2.5-fold above UNL.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treatment Arm - high dose ATGPatients agreeing to high dose ATG will be treated with 2 mg/kg daily on days -4 to 0. On days -4, -3 \& -2, ATG will be infused after fludarabine \& busulfan infusion. ATG will be infused over a minimum of 6 hrs on day -4 \& over at least 4 hrs on days -3, -2, -1 \& 0. Dose is based on actual body wt, \& rounded to nearest vial-Thymoglobulin is supplied in 25 mg vials, except if rounding would result in >5% difference from calculated dose. Foothills Medical Center Unit 57 standard practice followed for ATG infusion. ATG premeds include methylprednisolone, diphenhydramine, and an antipyretic. Meperidine 25-50 mg IVPB every 4 hours will be given as needed for rigors. MTX is given 15 mg/m2 IV on day +1 \& 10 mg/m2 on days +3, +6 \& +11 posttransplant. First dose of methotrexate is given on day +1, at least 24 hrs following end of infusion of stem cell product. | Drug | Treatment Arm - High dose ATG, Low dose CSA |
| Control Arm - standard of careThe historical controls will have received and the concurrent controls will receive our standard GVHD prophylaxis, ie, ATG 4.5 mg/kg i.v. (0.5 mg/kg on day -2, 2.0 mg/kg on day -1 and 2.0 mg/kg on day 0), MTX (15 mg/m2 i.v. on day 1 and 10 mg/m2 i.v. on days 3, 6 and 11) and CSA (2.5 mg/kg twice a day i.v. starting from day -1, adjusting dose to target trough plasma CSA levels of 200-400 microg/L, switching to oral formulation before discharge from peritransplant hospitalization, targeting the trough plasma levels of 200-400 microg/L until day 56, and tapering to zero between day 56 and 84). | Drug | Control Arm - Standard of care |
Primary outcome
moderate/severe chronic GVHD- and relapse-free survival (cGFRS) at 2 years post transplant
Time frame: 2 years
cGRFS will be compared between the study patients and the historical/concurrent controls using a Cox proportional hazards model to determine if administering high dose ATG + MTX and low dose CSA will be associated with improved cGRFS compared to historical/concurrent controls (4.5 mg/kg ATG + MTX + CSA).
1 secondary outcome
quality of life
Time frame: approximately 2 years (21 to 27 months) post transplant
Results and safety
The study was stopped early (reason given: Slow patient accrual and appearance of a toxicity). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Storek, MD principal investigator
Tom Baker Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Treatment Arm - high dose ATG in people with Graft-versus-host-disease and Relapse, run by AHS Cancer Control Alberta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow patient accrual and appearance of a toxicity). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
moderate/severe chronic GVHD- and relapse-free survival (cGFRS) at 2 years post transplant (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2025.