ATG Plus PTCy vs ATG for CGVHD Prophylaxis

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Leukemia; Myelodysplasia; Chronic Graft-versus-host-disease
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Anti-Thymocyte globulin (rabbit)

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 Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sarah Garisto, BSc; Phone Number: 1 416 634 8300; Email: sarah.garisto@ozmosisresearch.ca

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Recruiting
      • Kinghorn Cancer Centre, St Vincent's Health Network
      • Contact: Louise Christophersen
    • St. Leonards, New South Wales, Australia, 2065
      • Recruiting
      • Royal North Shore Hospital
      • Contact: Molly Forbes
  • Victoria
    • Melbourne, Victoria, Australia, 3121
      • Recruiting
      • Australasian Leukaemia and Lymphoma Group
      • Contact: Nada Hamad, MBBS MSc
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Recruiting
      • CancerCare Manitoba
      • Contact: Kristjan Paulson, MD
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Recruiting
      • Queen Elizabeth II Health Sciences Centre
      • Contact: Mahmoud Elsawy, MD
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Recruiting
      • Juravinski Hospital and Cancer Centre
      • Contact: Irwin Walker, MBBS; Phone Number: 76384 905 521 2100; Email: walkeri@mcmaster.ca
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • London Health Sciences Centre
      • Contact: Uday Deotare, MD
  • Quebec
    • Québec City, Quebec, Canada, G1R 2J6
      • Recruiting
      • Hôpital de L'Enfant-Jésus
      • Contact: Geneviève Gallagher, MD
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Recruiting
      • Saskatchewan Cancer Agency
      • Contact: Mohamed Elemary, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATG/PTCy; 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; Post Transplant Cyclophosphamide; Drug: Anti-Thymocyte globulin (rabbit); Anti-Thymocyte Globulin (rabbit, Thymoglobulin); Other Names: Thymoglobulin
Active Comparator: ATG; 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); Anti-Thymocyte Globulin (rabbit, Thymoglobulin); Other Names: Thymoglobulin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Sanofi; Ozmosis Research Inc.; Cell Therapy Transplant Canada
• Investigators: Principal Investigator: Irwin R Walker, MBBS, McMaster University; Principal Investigator: Kristjan Paulson, MD, CancerCare Manitoba

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2020
• Primary Completion (Anticipated): October 13, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: November 29, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (Actual): December 18, 2019

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: post transplant cyclophosphamide; anti-thymocyte globulin
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Preleukemia; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Thymoglobulin; Antilymphocyte Serum
• Other Study ID Numbers: CTTC1901; OZM-099 (Other Identifier: Ozmosis Research Inc)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes