Graft-vs-host DiseasePhase 2NCT01994824
Preemptive Therapy of GVHD
A Phase 2 study testing rabbit antithymocyte globulin in people with Graft-vs-host Disease, run by University of Calgary at 1 site in Canada.
Trial summary
Graft-vs-host disease (GVHD) causes substantial mortality, morbidity and poor quality of life after blood or marrow transplantation (BMT). In Alberta, we use antithymocyte globulin (ATG, given on days -2, -1 and 0) in addition to methotrexate and cyclosporine for GVHD prophylaxis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft-vs-host Disease
- What is being tested?
- rabbit antithymocyte globulin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2014to 27 Sep 2021
- 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 hematopoietic cell transplantation (second transplants are rare, typically performed for relapse of leukemia, in which case the likelihood of relapse is high, and there is the theoretical risk of increasing the likelihood further with ATG).
- Conditioning including ATG 4.5 mg/kg (the predictive value of IL15 and IL2Ra levels was determined in patients whose conditioning included 4.5 mg/kg or ATG).
- Age >17 (the predictive value of IL15 and IL2Ra levels has not been studied in children).
Who cannot join
- Nonmyeloablative conditioning (possible risk of ATG increasing relapse).
- Active viral infection (risk of worsening of the viral infection with ATG).
- Neutropenic fever with hypotension. In such case, the ATG can be given on day 9 (instead of day 8) if patient no longer has hypotension.
- Hypoxemia. In such case, the ATG can be given on day 9 (instead of day 8) if patient no longer has hypoxemia.
- History of anaphylactic reaction to Thymoglobulin or another rabbit blood protein.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Alberta Health Services-CancerControl / University of Calgary / University of Alberta (Edmonton)
Calgary, Alberta, T2N 4N1
About this study
Official title: Preemptive Therapy of Graft-vs-Host Disease Using Rabbit Antithymocyte Globulin
Graft-vs-host disease (GVHD) causes substantial mortality, morbidity and poor quality of life after blood or marrow transplantation (BMT). In Alberta, we use antithymocyte globulin (ATG, given on days -2, -1 and 0) in addition to methotrexate and cyclosporine for GVHD prophylaxis. In spite of that, ~40% patients develop significant GVHD (grade 2-4 acute GVHD or chronic GVHD needing systemic immunosuppressive therapy). ATG at the dose we typically use (4.5 mg/kg) is relatively non-toxic. At higher doses, ATG could increase the likelihood of posttransplant infections or relapse. Thus an extra dose of ATG (on top of the routine 4.5 mg/kg) might be justified only for patients at high risk of developing significant GVHD. In our experience, low serum level of interleukin-15 (IL15) and high serum level of interleukin-2 receptor alpha (IL2Ra) on day 7 predict development of significant GVHD. Here we will test whether, compared to historical/concurrent controls, an extra dose of ATG (3 mg/kg on day 8) given to patients with low IL15 or high IL2Ra on day 7 reduces the incidence of significant GVHD, and improves survival free of relapse and GVHD, and quality of life.
Read the detailed description
Blood for IL15 and IL2Ra determination will be drawn in the morning of day 7 (10 ml red top tube). IL15 and IL2Ra levels will be measured in Storek/Khan Lab by enzyme-linked immunosorbent assay (ELISA) as described (Pratt LM et al: BMT 2013). Storek/Khan Lab staff will report the IL15 and IL2Ra levels to the Bone Marrow Transplant ward (Unit 57, Foothills Medical Centre) no later than in the morning of day 8. If the IL15 level is <31 ng/L or the IL2Ra level is >4500 ng/L, the physician caring for the patient on the ward will order Thymoglobulin, 3 mg/kg intravenously, to be infused over 4-8 hours on day 8. The dose is based on actual body weight, and is rounded to the nearest vial (Thymoglobulin is supplied in 25 mg vials) except if the rounding would result in >5% difference from the calculated dose. Unit 57 standard practice will be followed for the infusion of ATG (see Standard Operation Procedure BMTS40153 ["ATG Administration"]). Premedication for ATG will include methylprednisolone 40 mg IVPB, acetaminophen 1000 mg PO and diphenhydramine 50 mg IVPB. Acetaminophen 1000 mg PO and diphenhydramine 50 mg IVPB can be repeated in 4-6 hours PRN flu-like symptoms/fever/chills. Meperidine 25-50 mg IVPB every 4 hours will be given PRN for rigors.
EVALUATIONS For the endpoint of the incidence of significant GVHD, patients will be followed per standard practice of the Alberta Blood and Marrow Transplant Program for the development of acute and chronic GVHD (www.albertahealthservices.ca/hp/if-hp-cancer-guide-bmt-manual.pdf). Per this standard practice, acute GVHD is graded according to Consensus criteria (Przepiorka D: BMT 1995) and chronic GVHD is diagnosed and graded according to NIH criteria (Filipovich AH: BBMT 2005). Significant GVHD is defined as grade 2-4 acute GVHD or chronic GVHD needing systemic immunosuppressive therapy.
For the endpoint of survival free of significant GVHD and relapse, relapse will be defined by standard criteria (eg, >5% marrow blasts by morphology in case of acute leukemia).
For the endpoint of quality of life at 2 years (21-27 months) posttransplant, Short Form 36 will be used.
- Conditions
- Graft-vs-host Disease
- Being tested
- rabbit antithymocyte globulin
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rabbit antithymocyte globulinDrug
Also called Thymoglobulin
Thymoglobulin, 3 mg/kg, will be given on day 8 posttransplant to patients at high risk of significant GVHD per day 7 IL15 and IL2Ra levels.
| Study group | Role | What they receive |
|---|---|---|
| Intervention arm | Experimental | Transplant recipients will have IL15 and IL2Ra measured on day 7. If at risk for significant GVHD, the patient will get rabbit antithymocyte globulin, 3 mg/kg on day 8.
Patients from this intervention/experimental arm will be compared to historical and concurrent controls (no ATG on day 8). Receives: Drug: rabbit antithymocyte globulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of significant GVHD
Measured: 2 years
Secondary outcomes (2)
Survival free of relapse and significant GVHD
Measured: 2 years
Quality of life measured by SF36
Short Form 36
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2013 (estimated)
- Study startJan 2014
- Primary completion30 Jun 2017
- Study completion27 Sep 2021
Why it stopped: The trend was observed toward higher mortality among the patients receiving the intervention Thymoglobulin on day 8 after hematopoietic cell transplantation.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Graft-vs-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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- University of Alberta, Alberta Health services
- Responsible party
- Principal investigator, Jan Storek, University of Calgary
- Investigators
- Jan Storek, MD, PhD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01994824
- Sponsor's protocol ID
- PreemptiveATG
- Status last verified
- Nov 2023
- First submitted
- 20 Nov 2013
- Last updated
- 30 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Khanolkar RA, Kalra A, Kinzel M, Pratt LM, Dharmani-Khan P, Chaudhry A, Williamson TS, Daly A, Morris DG, Khan FM, Storek J. A biomarker-guided, prospective, phase 2 trial of pre-emptive graft-versus-host disease therapy using anti-thymocyte globulin. Cytotherapy. 2021 Nov;23(11):1007-1016. doi: 10.1016/j.jcyt.2021.06.003. Epub 2021 Aug 6.
PubMed 34373186
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preemptive Therapy of Graft-vs-Host Disease Using Rabbit Antithymocyte Globulin
- ClinicalTrials.gov ID
- NCT01994824
- Acronym / sponsor ID
- PreemptiveATG
- Conditions
- Graft-vs-host Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trend was observed toward higher mortality among the patients receiving the intervention Thymoglobulin on day 8 after hematopoietic cell transplantation.
- Enrolment
- 70 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- University of Alberta, Alberta Health services
- Study start
- Jan 2014 (actual)
- Primary completion
- 30 Jun 2017 (actual)
- Study completion
- 27 Sep 2021 (actual)
- First posted
- 26 Nov 2013 (estimated)
- 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.
Graft-vs-host disease (GVHD) causes substantial mortality, morbidity and poor quality of life after blood or marrow transplantation (BMT). In Alberta, we use antithymocyte globulin (ATG, given on days -2, -1 and 0) in addition to methotrexate and cyclosporine for GVHD prophylaxis. In spite of that, ~40% patients develop significant GVHD (grade 2-4 acute GVHD or chronic GVHD needing systemic immunosuppressive therapy). ATG at the dose we typically use (4.5 mg/kg) is relatively non-toxic. At higher doses, ATG could increase the likelihood of posttransplant infections or relapse. Thus an extra dose of ATG (on top of the routine 4.5 mg/kg) might be justified only for patients at high risk of developing significant GVHD. In our experience, low serum level of interleukin-15 (IL15) and high serum level of interleukin-2 receptor alpha (IL2Ra) on day 7 predict development of significant GVHD. Here we will test whether, compared to historical/concurrent controls, an extra dose of ATG (3 mg/kg on day 8) given to patients with low IL15 or high IL2Ra on day 7 reduces the incidence of significant GVHD, and improves survival free of relapse and GVHD, and quality of life.
Detailed description
Blood for IL15 and IL2Ra determination will be drawn in the morning of day 7 (10 ml red top tube). IL15 and IL2Ra levels will be measured in Storek/Khan Lab by enzyme-linked immunosorbent assay (ELISA) as described (Pratt LM et al: BMT 2013). Storek/Khan Lab staff will report the IL15 and IL2Ra levels to the Bone Marrow Transplant ward (Unit 57, Foothills Medical Centre) no later than in the morning of day 8. If the IL15 level is <31 ng/L or the IL2Ra level is >4500 ng/L, the physician caring for the patient on the ward will order Thymoglobulin, 3 mg/kg intravenously, to be infused over 4-8 hours on day 8. The dose is based on actual body weight, and is rounded to the nearest vial (Thymoglobulin is supplied in 25 mg vials) except if the rounding would result in >5% difference from the calculated dose. Unit 57 standard practice will be followed for the infusion of ATG (see Standard Operation Procedure BMTS40153 ["ATG Administration"]). Premedication for ATG will include methylprednisolone 40 mg IVPB, acetaminophen 1000 mg PO and diphenhydramine 50 mg IVPB. Acetaminophen 1000 mg PO and diphenhydramine 50 mg IVPB can be repeated in 4-6 hours PRN flu-like symptoms/fever/chills. Meperidine 25-50 mg IVPB every 4 hours will be given PRN for rigors.
EVALUATIONS For the endpoint of the incidence of significant GVHD, patients will be followed per standard practice of the Alberta Blood and Marrow Transplant Program for the development of acute and chronic GVHD (www.albertahealthservices.ca/hp/if-hp-cancer-guide-bmt-manual.pdf). Per this standard practice, acute GVHD is graded according to Consensus criteria (Przepiorka D: BMT 1995) and chronic GVHD is diagnosed and graded according to NIH criteria (Filipovich AH: BBMT 2005). Significant GVHD is defined as grade 2-4 acute GVHD or chronic GVHD needing systemic immunosuppressive therapy.
For the endpoint of survival free of significant GVHD and relapse, relapse will be defined by standard criteria (eg, >5% marrow blasts by morphology in case of acute leukemia).
For the endpoint of quality of life at 2 years (21-27 months) posttransplant, Short Form 36 will be used.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention arm | Experimental | Drug: rabbit antithymocyte globulinTransplant recipients will have IL15 and IL2Ra measured on day 7. If at risk for significant GVHD, the patient will get rabbit antithymocyte globulin, 3 mg/kg on day 8. Patients from this intervention/experimental arm will be compared to historical and concurrent controls (no ATG on day 8). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- First allogeneic hematopoietic cell transplantation (second transplants are rare, typically performed for relapse of leukemia, in which case the likelihood of relapse is high, and there is the theoretical risk of increasing the likelihood further with ATG).
- Conditioning including ATG 4.5 mg/kg (the predictive value of IL15 and IL2Ra levels was determined in patients whose conditioning included 4.5 mg/kg or ATG).
- Age >17 (the predictive value of IL15 and IL2Ra levels has not been studied in children).
Key exclusion criteria (5 listed)
- Nonmyeloablative conditioning (possible risk of ATG increasing relapse).
- Active viral infection (risk of worsening of the viral infection with ATG).
- Neutropenic fever with hypotension. In such case, the ATG can be given on day 9 (instead of day 8) if patient no longer has hypotension.
- Hypoxemia. In such case, the ATG can be given on day 9 (instead of day 8) if patient no longer has hypoxemia.
- History of anaphylactic reaction to Thymoglobulin or another rabbit blood protein.
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 |
|---|---|---|
| rabbit antithymocyte globulinAlso: ThymoglobulinThymoglobulin, 3 mg/kg, will be given on day 8 posttransplant to patients at high risk of significant GVHD per day 7 IL15 and IL2Ra levels. | Drug | Intervention arm |
Primary outcome
Cumulative incidence of significant GVHD
Time frame: 2 years
2 secondary outcomes
Survival free of relapse and significant GVHD
Time frame: 2 years
Quality of life measured by SF36
Time frame: 2 years
Results and safety
The study was stopped early (reason given: The trend was observed toward higher mortality among the patients receiving the intervention Thymoglobulin on day 8 after hematopoietic cell transplantation.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2023.
- Derived from this study: PubMed 34373186Khanolkar RA, Kalra A, Kinzel M, Pratt LM, Dharmani-Khan P, Chaudhry A, Williamson TS, Daly A, Morris DG, Khan FM, Storek J. A biomarker-guided, prospective, phase 2 trial of pre-emptive graft-versus-host disease therapy using anti-thymocyte globulin. Cytotherapy. 2021 Nov;23(11):1007-1016. doi: 10.1016/j.jcyt.2021.06.003. Epub 2021 Aug 6.
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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, PhD principal investigator
University of Calgary
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 rabbit antithymocyte globulin in people with Graft-vs-host Disease, run by University of Calgary 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 3 inclusion and 5 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 30 Nov 2023. 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: The trend was observed toward higher mortality among the patients receiving the intervention Thymoglobulin on day 8 after hematopoietic cell transplantation.). 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?
Cumulative incidence of significant GVHD (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01994824, which also lists 1 linked publication.
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 30 Nov 2023.