ATG Plus PTCy vs ATG for CGVHD Prophylaxis

Phase 2

Active, not recruiting

• Conditions: Myelodysplasia; Chronic Graft-versus-host-disease; Acute Leukemia
• Interventions: Drug: Cyclophosphamide; Drug: Anti-Thymocyte globulin (rabbit)

• Registration Number: NCT04202835
• Lead Sponsor: McMaster University

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2019-11-29
• Study First Submitted QC: 2019-12-17
• Study First Posted: 2019-12-18
• Study Start: 2020-10-14
• Primary Completion: 2024-05-18
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-11
• Study Completion: 2026-02-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. The participant is aged ≥ 16 and deemed medically fit per investigator for protocol
2. The participant has either acute myeloid leukemia in 1st or 2nd complete remission (CR), or has myelodysplastic syndrome
3. The participant will receive a blood progenitor cell graft ("HPC, Apheresis")
4. The participant has a related or unrelated donor, who is fully MHC matched with the recipient at HLA-A, B, C and DRB1.
5. The participant meets the transplant centre's criteria for transplantation, using either myeloablative or reduced intensity conditioning.
6. The participant has good performance status (Karnofsky ≥60%)
7. The participant is able to understand and sign the informed consent form
8. Ability and willingness to comply with study procedures and schedule, in the Investigator's opinion.
9. The participant is receiving their first transplant

Exclusion Criteria

1. The participant is HIV antibody positive
2. The participant has a hypersensitivity to rabbit proteins or Thymoglobulin® pharmaceutical excipients, glycine or mannitol.
3. The participant has active or chronic infection (i.e. infection requiring oral or IV therapy)
4. The participant (if female and of childbearing potential) is pregnant or breast-feeding at the time of enrollment
5. 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
6. 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
7. The participant has urinary outflow obstruction
8. The participant is in poor condition (determined per institutional guidelines)
9. The participant has acute leukemia in relapse
10. The participant has myelodysplastic syndrome with > 10% marrow blasts
11. The participant is having their second transplant
12. The participant is taking T-cell antibody prophylaxis (anti-CD52)
13. The participant is receiving a cord blood graft or T-cell depleted grafts
14. The participant has mixed phenotype acute leukemia
15. 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.
16. The participant is in complete remission with incomplete recovery (CRi)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ATG/PTCy	Anti-Thymocyte globulin (rabbit)	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.
ATG/PTCy	Cyclophosphamide	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.
ATG	Anti-Thymocyte globulin (rabbit)	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).

Primary Outcome Measures

Name	Time	Method
Registration of 80 patients within twenty four months	24 months	Registration will be documented by the Clinical Research Organization (Ozmosis Research Inc.)

Secondary Outcome Measures

Name	Time	Method
CRFS	27 months	Chronic graft versus host disease free- and relapse-free survival (CRFS)
GRFS	27 months	Graft versus host disease-, and relapse-, free survival (GRFS)
Cost of study	27 months	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.
Survival	27 months	Survival (dead/alive) at 100 days for each patient
Complete data collection	27 months	The Clinical Research Organization (Ozmosis Research Inc.) will document completeness of data collection

Trial Locations

Locations (9)

Kinghorn Cancer Centre, St Vincent's Health Network; 🇦🇺 Darlinghurst, New South Wales, Australia

Royal North Shore Hospital; 🇦🇺 St. Leonards, New South Wales, Australia

Australasian Leukaemia and Lymphoma Group; 🇦🇺 Melbourne, Victoria, Australia

CancerCare Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

Queen Elizabeth II Health Sciences Centre; 🇨🇦 Halifax, Nova Scotia, Canada

Juravinski Hospital and Cancer Centre; 🇨🇦 Hamilton, Ontario, Canada

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Hôpital de l'Enfant-Jésus; 🇨🇦 Québec City, Quebec, Canada

Saskatchewan Cancer Agency; 🇨🇦 Saskatoon, Saskatchewan, Canada