High Dose Thymoglobulin for Graft-versus-Host Disease Prophylaxis
(ATG2017 Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: AHS Cancer Control Alberta
Must be taking: ATG, CSA, MTX
Must not be taking: Anti-tuberculosis drugs
Disqualifiers: Myelofibrosis, HIV, Severe obesity, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves specific treatments and conditions, it's best to discuss your current medications with the trial team to ensure there are no conflicts.
What data supports the effectiveness of the drug Thymoglobulin for preventing graft-versus-host disease?
Research shows that Thymoglobulin, a type of rabbit antithymocyte globulin, is commonly used in stem cell transplants to reduce the risk of graft-versus-host disease. Studies indicate that it is effective in preventing both acute and chronic forms of this condition, with similar efficacy to other formulations in terms of survival rates.
12345Is high dose Thymoglobulin generally safe for humans?
Thymoglobulin, also known as rabbit antithymocyte globulin, is generally used to prevent or treat conditions like organ rejection and graft-versus-host disease. While it can cause serum sickness (a type of immune reaction) in most patients without additional drugs, serious allergic reactions are rare. Adverse events during infusion may occur but are not significantly different from other similar treatments.
13567How is Thymoglobulin different from other drugs for preventing graft-versus-host disease?
Thymoglobulin is unique because it is a rabbit-derived polyclonal antibody used to suppress the immune system, which helps prevent graft-versus-host disease after stem cell transplants. Unlike other treatments, it is specifically designed to target and reduce the activity of T-cells (a type of immune cell), and its dosage and preparation can vary to optimize patient outcomes.
12389Eligibility Criteria
This trial is for adults over 17 who need their first blood stem cell transplant due to a blood cancer. They must have an HLA matched sibling or almost fully matched unrelated donor, and meet specific health criteria like normal liver function tests. People with previous transplants, certain infections (HIV, high-risk CMV), contact with tuberculosis, severe obesity, or women who are pregnant/breastfeeding or not using contraception can't join.Inclusion Criteria
I am over 17 and getting my first stem cell transplant for blood cancer with a specific treatment plan.
Exclusion Criteria
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. 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. 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). Hypersensitivity to rabbit blood protein, Thymoglobulin or a Thymoglobulin excipient. Severe obesity, defined as body mass index ≥40 kg/m2. The reason is that obese patients are at risk of achieving a high ATG area under the time vs concentration curve (AUC). 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 Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
High dose ATG is infused on days -4, -3, -2, -1, and 0. CSA is given from day 21 to 84, and methotrexate is administered on days 1, 3, 6, and 11.
12 weeks
Multiple visits for infusions and monitoring
Follow-up
Participants are monitored for the development of acute and chronic GVHD, and for relapse. Quality of life is assessed 2 years post-transplant.
2 years
Participant Groups
The study compares two approaches to prevent graft-versus-host disease after a stem cell transplant: the usual low dose of Thymoglobulin plus standard drugs versus a high dose of Thymoglobulin with a lower dose of these drugs. The goal is to see if the higher Thymoglobulin dose better prevents relapse and chronic disease without increasing other complications.
2Treatment groups
Experimental Treatment
Group I: Treatment Arm - High dose ATG, Low dose CSAExperimental Treatment1 Intervention
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.
Group II: Control Arm - Standard of careExperimental Treatment1 Intervention
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.
Thymoglobulin is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Thymoglobulin for:
- Prophylaxis and treatment of renal transplant acute rejection in conjunction with concomitant immunosuppression
- Severe aplastic anemia
🇪🇺 Approved in European Union as Thymoglobulin for:
- Prevention and treatment of acute cellular rejection after renal transplantation
- Severe aplastic anemia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Tom Baker Cancer Centre/Arthur J.E. Child Comprehensive Cancer CentreCalgary, Canada
Tom Baker Cancer CentreCalgary, Canada
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Who Is Running the Clinical Trial?
AHS Cancer Control AlbertaLead Sponsor
References
Anti-Gal and Anti-Neu5Gc Responses in Nonimmunosuppressed Patients After Treatment With Rabbit Antithymocyte Polyclonal IgGs. [2022]Polyclonal antihuman thymocyte rabbit IgGs (antithymocyte globulin [ATG]) are popular immunosuppressive drugs used to prevent or treat organ or bone-marrow allograft rejection, graft versus host disease, and autoimmune diseases. However, animal-derived glycoproteins are also strongly immunogenic and rabbit ATG induces serum sickness disease in almost all patients without additional immunosuppressive drugs, as seen in the Study of Thymoglobulin to arrest Type 1 Diabetes (START) trial of ATG therapy in new-onset type 1 diabetes.
Clinical impact of anti-thymocyte globulin on survival and graft-versus-host disease in patients undergoing human leukocyte antigen mismatched allogeneic stem cell transplantation. [2021]Rabbit anti-thymocyte globulin (ATG) is usually incorporated in hematopoietic stem cell transplantation (HSCT) to reduce the incidence of graft-versus-host disease (GVHD). This study aimed to find optimal ATG doses in patients undergoing human leukocyte antigen (HLA)-mismatched allogeneic HSCT.
Comparison of different rabbit ATG preparation effects on early lymphocyte subset recovery after allogeneic HSCT and its association with EBV-mediated PTLD. [2021]Rabbit antithymocyte globulin (ATG) is commonly used before allogeneic hematopoietic stem cell transplantation (allo-HSCT) to prevent graft-versus-host disease. Studies comparing the effect of different ATG preparations and dosages on immune reconstitution and risk for Epstein-Barr virus (EBV)-mediated post-transplant lymphoproliferative disorder (PTLD) are rare.
Comparison of Different Rabbit Anti-Thymocyte Globulin Formulations in Allogeneic Stem Cell Transplantation: Systematic Literature Review and Network Meta-Analysis. [2018]Since 2000, various phase III randomized controlled trials (RCTs) have investigated the efficacy of rabbit antithymocyte globulin (ATG) in patients following allogeneic stem cell transplantation (allo-SCT). Comparisons of different ATG formulations are lacking, however. Our aim was to synthesize all published efficacy evidence to enable a comparison of all available formulations of rabbit ATG in the allo-SCT setting. We performed a systematic literature review to identify all available phase III RCT evidence. We searched the Cochrane Library, MEDLINE, MEDLINE In-Process, and the website www.ClinicalTrials.gov. In addition, a trial presented at the Annual Meeting of the American Society of Hematology 2016 was added to include the most recent evidence. We identified a total of 6 RCTs, including 2 formulations: anti-T lymphocyte globulin (ATLG; Grafalon, Neovii Biotech, Lexington, MA) and polyclonal globulin immunized with human thymocytes (Thymoglobulin [Thymo]; Genzyme-Sanofi, Cambridge, MA). The evidence was synthesized using a conventional network meta-analysis (NMA). The best treatment for preventing graft-versus-host disease (GVHD) was ATLG, which had a more favorable hazard ratio (HR) compared with standard treatment (chronic GVHD: HR, .42; 95% confidence interval [CI], .31 to .56; acute GVHD grade II-IV: HR, .54; 95% CI, .39 to .73; acute GVHD grade III-IV: HR, .50; 95% CI, .29 to .86), whereas both ATLG and Thymo were at least similarly effective in terms of transplantation-related mortality (TRM) (ATLG: HR, .90; 95% CI, .61 to 1.32; Thymo: HR, .90; 95% CI, .56 to 1.44). Thymo tended to be the better treatment option regarding overall survival (OS) (HR, .86; 95% CI, .59 to 1.26). Our NMA provides the first report of the relative efficacy of all available rabbit ATG formulations in patients undergoing allo-SCT. Until additional data from randomized head-to-head comparisons are available, based on the present analysis, ATLG seems to be the best option to prevent chronic and acute GVHD. Both formulations show similar efficacy in terms of TRM, whereas Thymo appears to be the better treatment option in terms of OS.
Assessment of batch to batch variation in polyclonal antithymocyte globulin preparations. [2014]Antithymocyte globulins (ATGs) are used to prevent and treat allograft rejection and graft versus host disease. They are purified IgG fractions derived from rabbits immunized with the Jurkat T-cell line (ATG-Fresenius) or thymus cells (Thymoglobulin). Differences not only in the amounts of leukocyte reactive antibodies but also in the antigens targeted by ATGs could potentially affect the clinical efficacy of different batches of these polyclonal antibody preparations.
An avoidable cause of thymoglobulin anaphylaxis. [2020]Thymoglobulin® (anti-thymocyte globulin [rabbit]) is a purified pasteurised, gamma immune globulin obtained by immunisation of rabbits with human thymocytes. Anaphylactic allergic reactions to a first injection of thymoglobulin are rare.
Comparing Two Types of Rabbit ATG prior to Reduced Intensity Conditioning Allogeneic Hematopoietic SCT for Hematologic Malignancies. [2020]Different rabbit polyclonal antilymphocyte globulins (ATGs) are used in allogeneic hematopoietic stem cell transplantation (alloHSCT) to prevent graft-versus-host disease (GvHD). We compared 2 different ATGs in alloHSCT after reduced intensity conditioning (RIC) for hematological malignancies. We reviewed 30 alloHSCT for hematologic malignancies performed between 2007 and 2010 with fludarabine and i.v. busulfan as conditioning regimen. Patients alternatingly received Thymoglobulin or ATG-F. Median followup was 3.3 (2.5-4.5) years. Adverse events appeared to occur more frequently during Thymoglobulin infusion than during ATG-F infusion but without statistical significance (P = 0.14). There were also no differences in 3-year overall survival (OS), disease-free survival (DFS), relapse incidence, and transplant related mortality (TRM) in the Thymoglobulin versus ATG-F group: 45.7% versus 46.7%, 40% versus 33.7%, 40% versus 33.3%, and 20% versus 33.3%. The same held for graft failure, rejection, infectious complications, immune reconstitution, and acute or chronic GvHD. In patients transplanted for hematologic malignancies after RIC, the use of Thymoglobulin is comparable to that of ATG-F in all the aspects evaluated in the study. However due to the small number of patients in each group we cannot exclude a possible difference that may exist.
In vivo characterization of rabbit anti-mouse thymocyte globulin: a surrogate for rabbit anti-human thymocyte globulin. [2021]Polyclonal rabbit anti-human thymocyte globulin (Thymoglobulin) is used clinically for immunosuppression in solid organ transplantation; however, it is difficult to fully characterize the effects of this agent in humans.
Comparison of 2 Different Doses of Antithymocyte Globulin in Conditioning Regimens for Haploidentical Hematopoietic Stem Cell Transplantation. [2022]Antithymocyte globulin is extensively used for prophylaxis of graft-versus-host disease in patients undergoing haploidentical hematopoietic stem cell transplantation. However, different doses of antithymocyte globulin are administered in clinical practice. This study aimed to identify the optimal dose of antithymocyte globulin (thymoglobulin) in haploidentical hematopoietic stem cell transplantation.