Background and Rationale
Both antithymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) are widely used as graft-versus-host disease (GVHD) prophylaxis strategies in allogeneic hematopoietic cell transplantation (HCT). Each approach independently reduces the risk of acute and chronic GVHD without significantly compromising relapse rates.
We demonstrated with the CTTC 1901 trial the safety of this combination approach, with no increased toxicity seen, and lower rates of acute GVHD demonstrated. A definitive trial showing improvement in chronic GVHD, relapse free survival would be required to change practice.
This trial addresses this critical knowledge gap using a pragmatic design that reflects real-world decision-making and allows for center-specific standards, making it both feasible and broadly generalizable.
Study Design
• Design: Multicenter, pragmatic, open-label randomized controlled trial
• Randomization unit: Individual patient
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• Physician-driven stratification: Each site/physician selects either ATG or PTCy as their preferred standard GVHD prophylaxis based on local practice and patient-specific factors
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• Randomization: Patients are randomized 1:1 to either:
o Arm A: Physician-selected standard prophylaxis (ATG or PTCy), or
o Arm B: Combination of ATG + PTCy
This design respects physician judgment and enhances participation while directly testing the incremental benefit of dual immunosuppression.