HIgh Dose Thymoglobulin Instead of Cyclosporine With a Low Dose of Thymoglobulin for GVHD Prophylaxis (ATG2017)
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|ClinicalTrials.gov Identifier: NCT03456817|
Recruitment Status : Not yet recruiting
First Posted : March 7, 2018
Last Update Posted : June 29, 2018
|Condition or disease||Intervention/treatment||Phase|
|Graft-versus-host-disease Relapse||Drug: Treatment Arm - high dose ATG Drug: Control Arm - standard of care||Phase 2|
There are a number of complications of allogeneic hematopoietic cell transplantation.
The main complications are:
- Recurrence (relapse) of the disease for which the transplantation is done (for example, leukemia). The relapse 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), no CSA (instead of CSA from day -1 through 84) will be given, 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Graft-vs-host Disease Prophylaxis With High Dose Thymoglobulin (10 mg/kg) and Methotrexate in Comparison to Historical/Concurrent Controls Who Received Thymoglobulin (4.5 mg/kg), Methotrexate and Cyclosporine|
|Estimated Study Start Date :||October 2018|
|Estimated Primary Completion Date :||September 2023|
|Estimated Study Completion Date :||September 2023|
Experimental: Treatment Arm - high dose ATG
High dose ATG at 10 mg/kg 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), acetaminophen (Tylenol) 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. No CSA (cyclosporine A) will be given. Standard dose methotrexate will be given.
Drug: Treatment Arm - high dose ATG
Patients agreeing to 10 mg/kg 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 40 mg IVPB, acetaminophen 1000 mg PO & diphenhydramine 50 mg IVPB. Acetaminophen 1000 mg PO & diphenhydramine 50 mg IVPB can be repeated in 4-6 hrs PRN for flu-like symptoms/fever/chills. Meperidine 25-50 mg IVPB given PRN every 4 hrs 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 care
Low dose ATG (thymoglobulin) at 4.5 mg/kg 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.
Drug: Control Arm - standard of care
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).
- 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 10 mg/kg ATG + MTX and no CSA will be associated with improved cGRFS compared to historical/concurrent controls (4.5 mg/kg ATG + MTX + CSA).
- quality of life [ Time Frame: approximately 2 years (21 to 27 months) post transplant ]each scale (domain) of the short form-36 (SF36) questionnaire will be compared between the 10 mg/kg 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 10 mg/kg ATG patients compared to the controls (due to the reduction of cGVHD).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03456817
|Contact: Jan Storek, MDfirstname.lastname@example.org|
|Principal Investigator:||Jan Storek, MD||Tom Baker Cancer Centre|