Status:
TERMINATED
HIgh Dose Thymoglobulin Instead of Cyclosporine With a Low Dose of Thymoglobulin for GVHD Prophylaxis
Lead Sponsor:
AHS Cancer Control Alberta
Conditions:
Graft-versus-host-disease
Relapse
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
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 increasi...
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...
Eligibility Criteria
Inclusion
- First allogeneic HCT, performed for a hematologic malignancy, using filgrastim-mobilized peripheral blood stem cells (PBSC).
- 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.
- Planned GVHD prophylaxis with our standard of low-dose ATG (4.5 mg/kg) + MTX + high-dose CSA.
- HLA matched sibling donor, or ≥7/8 HLA allele-matched unrelated donor (maximum 1 allele mismatch at HLA-A, B, C, or DRB1).
- Age \>17 years.
Exclusion
- 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.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
- High risk of PTLD based on donor positive AND recipient negative Epstein-Barr virus (EBV) serostatus (EBNA1 or VCA IgG)80
- Hypersensitivity to rabbit blood protein, Thymoglobulin or a Thymoglobulin excipient.
- 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.
- 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.
Key Trial Info
Start Date :
July 1 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 31 2025
Estimated Enrollment :
68 Patients enrolled
Trial Details
Trial ID
NCT03456817
Start Date
July 1 2020
End Date
May 31 2025
Last Update
July 18 2025
Active Locations (1)
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1
Tom Baker Cancer Centre/Arthur J.E. Child Comprehensive Cancer Centre
Calgary, Alberta, Canada