HIgh Dose Thymoglobulin Instead of Cyclosporine With a Low Dose of Thymoglobulin for GVHD Prophylaxis (ATG2017)

July 16, 2025 updated by: AHS Cancer Control Alberta

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
68

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
        • Tom Baker Cancer Centre/Arthur J.E. Child Comprehensive Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. First allogeneic HCT, performed for a hematologic malignancy, using filgrastim-mobilized peripheral blood stem cells (PBSC).
  2. 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.
  3. Planned GVHD prophylaxis with our standard of low-dose ATG (4.5 mg/kg) + MTX + high-dose CSA.
  4. HLA matched sibling donor, or ≥7/8 HLA allele-matched unrelated donor (maximum 1 allele mismatch at HLA-A, B, C, or DRB1).
  5. Age >17 years.

Exclusion Criteria:

  1. Nonmyeloablative conditioning.
  2. Cord blood or marrow graft.
  3. Myelofibrosis being the primary indication for HCT.
  4. Previous autologous or allogeneic HCT.
  5. Total Bilirubin >1.5-fold above upper normal limit (UNL), ALT >2.0-fold above UNL, or alkaline phosphatase >2.5-fold above UNL.
  6. HIV positive by a serologic test that includes detection of both antibody and antigen)
  7. 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.
  8. 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
  9. High risk of PTLD based on donor positive AND recipient negative Epstein-Barr virus (EBV) serostatus (EBNA1 or VCA IgG)80
  10. Hypersensitivity to rabbit blood protein, Thymoglobulin or a Thymoglobulin excipient.
  11. 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.

  12. Contraindication to methotrexate:

    1. Hypersensitivity to methotrexate or to any ingredient in the formulation or component of the container.
    2. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment Arm - High dose ATG, Low dose CSA
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.
Drug: Treatment Arm - high dose ATG
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.
Other: Control Arm - Standard of care
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.
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).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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 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).
approximately 2 years (21 to 27 months) post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AHS Cancer Control Alberta

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jan Storek, MD, Tom Baker Cancer Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 1, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 7, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 18, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ATG2017

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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