ATG Plus PTCy vs ATG for CGVHD Prophylaxis

Study Overview
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Brief Summary
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A Randomized Pilot Trial to test the feasibility of comparing anti-thymocyte globulin plus post transplant cyclophosphamide with anti-thymocyte globulin alone to prevent chronic graft versus host disease.

Detailed Description
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Patients with acute leukemia or myelodysplastic syndrome will be randomized to receive, or not receive, post transplant cyclophosphamide in addition to anti-thymocyte globulin.

Official Title
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A Randomized Pilot Trial Comparing Anti-Thymocyte Globulin (ATG) With ATG Plus Post Transplant Cyclophosphamide (PTCy) for Prophylaxis Against Acute and Chronic Graft Versus Host Disease (GVHD)

Conditions
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Acute Leukemia, Myelodysplasia, Chronic Graft-versus-host-disease

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Anti-Thymocyte globulin (rabbit)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant is aged ≥ 16 and deemed medically fit per investigator for protocol The participant has either acute myeloid leukemia in 1st or 2nd complete remission (CR), or has myelodysplastic syndrome The participant will receive a blood progenitor cell graft (HPC, Apheresis) The participant has a related or unrelated donor, who is fully MHC matched with the recipient at HLA-A, B, C and DRB1. The participant meets the transplant centre's criteria for transplantation, using either myeloablative or reduced intensity conditioning. The participant has good performance status (Karnofsky ≥60%) The participant is able to understand and sign the informed consent form Ability and willingness to comply with study procedures and schedule, in the Investigator's opinion. The participant is receiving their first transplant Exclusion Criteria: The participant is HIV antibody positive The participant has a hypersensitivity to rabbit proteins or Thymoglobulin® pharmaceutical excipients, glycine or mannitol. The participant has active or chronic infection (i.e. infection requiring oral or IV therapy) The participant (if female and of childbearing potential) is pregnant or breast-feeding at the time of enrollment The participant (if female and of childbearing potential) does not agree to use an adequate contraceptive method from the time of enrollment until a minimum of one year following transplant3 The participant (if male and fertile) does not agree to use an adequate contraceptive method from the time of enrollment until a minimum of one year following transplant3 The participant has urinary outflow obstruction The participant is in poor condition (determined per institutional guidelines) The participant has acute leukemia in relapse The participant has myelodysplastic syndrome with > 10% marrow blasts The participant is having their second transplant The participant is taking T-cell antibody prophylaxis (anti-CD52) The participant is receiving a cord blood graft or T-cell depleted grafts The participant has mixed phenotype acute leukemia The participant has prior malignancies, except resected nonmelanoma or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent < 5 years previously must be reviewed and approved by the sponsors. The participant is in complete remission with incomplete recovery (CRi)

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized pilot trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATG/PTCy<br>Anti-Thymocyte Globulin (ATG, Thymoglobulin) 4.5 mg/kg IV (divided 0.5, 2.0, 2.0 mg/kg on days -2, -1 and +1); cyclophosphamide (Post Transplant Cyclophosphamide, PTCy) 50 mg/kg IV daily on days +3 and +4. | Drug: Cyclophosphamide<br>* Post Transplant Cyclophosphamide<br>Drug: Anti-Thymocyte globulin (rabbit)<br>* Anti-Thymocyte Globulin (rabbit, Thymoglobulin)<br>* Other names: Thymoglobulin;|
| Active Comparator: ATG<br>Anti-Thymocyte Globulin (ATG, Thymoglobulin) 4.5 mg/kg IV (divided 0.5, 2.0, 2.0 mg/kg on days -2, -1 and +1). | Drug: Anti-Thymocyte globulin (rabbit)<br>* Anti-Thymocyte Globulin (rabbit, Thymoglobulin)<br>* Other names: Thymoglobulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Registration of 80 patients within twenty four months | Registration will be documented by the Clinical Research Organization (Ozmosis Research Inc.) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRFS | Chronic graft versus host disease free- and relapse-free survival (CRFS) | 27 months | 
| GRFS | Graft versus host disease-, and relapse-, free survival (GRFS) | 27 months | 
| Survival | Survival (dead/alive) at 100 days for each patient | 27 months | 
| Complete data collection | The Clinical Research Organization (Ozmosis Research Inc.) will document completeness of data collection | 27 months | 
| Cost of study | The sponsor (McMaster University) and the Clinical Research Organization (Ozmosis Research Inc.) will compare actual total trial costs in Canadian dollars at trial completion (at completion of outcomes analysis and report) with expected costs as determined for the trial budget. | 27 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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post transplant cyclophosphamide, anti-thymocyte globulin