NCT03456817

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

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 68 (actual)
• Sponsor: AHS Cancer Control Alberta · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 increasing the chances of other transplant complications.

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.

Conditions

• Graft-versus-host-disease
• Relapse

Interventions

Type	Name	Description
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.
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).

Timeline

• Start date: 2020-07-01
• Primary completion: 2025-05-31
• Completion: 2025-05-31
• First posted: 2018-03-07
• Last updated: 2025-07-18

Locations

1 site across 1 country: Canada