TAC/MTX vs. TAC/MMF/PTCY for Prevention of Graft-versus-Host Disease and Microbiome and Immune Reconstitution Study (BMT CTN 1703/1801)

Summary

1703: The study is designed as a randomized, phase III, multicenter trial comparing two acute graft-versus-host disease (aGVHD) prophylaxis regimens: tacrolimus/methotrexate (Tac/MTX) versus post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) in the setting of reduced intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation. 1801: The goal of this protocol is to test the primary hypothesis that the engraftment stool microbiome diversity predicts one-year non-relapse mortality in patients undergoing reduced intensity allogeneic HCT.

Timeline

Start

2019-06-25

Primary completion

2022-09-19

Completion

2022-09-19

Outcome

Met primary endpoint

registry PTCY/Tacrolimus/MMF vs Tacrolimus/Methotrexate; p = 0.001; Hazard Ratio (HR) 0.641 (95% CI 0.492 to 0.835) NCT03959241 ↗

paper Overall study results revealed superior GVHD-free, relapse-free survival (GRFS) with PTCy-based prophylaxis. PMID 40305657 ↗

Publications

• Background Bolanos-Meade J, Hamadani M, Wu J, Al Malki MM, Martens MJ, Runaas L, Elmariah H, Rezvani AR, Gooptu M, Larkin KT, Shaffer BC, El Jurdi N, Loren AW, Solh M, Hall AC, Alousi AM, Jamy OH, Perales MA, Yao JM, Applegate K, Bhatt AS, Kean LS, Efebera YA, Reshef R, Clark W, DiFronzo NL, Leifer E, Horowitz MM, Jones RJ, Holtan SG; BMT CTN 1703 Investigators. Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis. N Engl J Med. 2023 Jun 22;388(25):2338-2348. doi: 10.1056/NEJMoa2215943.
• Abedin S, Martens MJ, Bolanos-Meade J, Al Malki MM, Lian Q, Runaas L, Elmariah H, Gooptu M, Larkin KT, Shaffer BC, Loren AW, Solh M, Alousi AM, Jamy OH, Perales MA, Rezvani A, Bhatt A, El Jurdi N, Yao JM, Applegate K, Kean LS, Efebera YA, Reshef R, Clark W, Leifer E, Saber W, Horowitz MM, Jones RJ, Holtan SG, Hamadani M. Impact of posttransplant cyclophosphamide-based GVHD prophylaxis in patients 70 years and older: an update from BMT CTN 1703. Blood Adv. 2025 Jul 22;9(14):3495-3501. doi: 10.1182/bloodadvances.2025015964.
• Holtan SG, Bolanos-Meade J, Al Malki MM, Wu J, Kitko CL, Reshef R, Rezvani AR, Shaffer BC, Solh MM, Yao JM, Runaas L, Elmariah H, Larkin KT, El Jurdi N, Gooptu M, Loren AW, Hall AC, Alousi AM, Jamy O, Clark W, Kean L, Bhatt AS, Perales MA, Applegate K, Efebera YA, Leifer E, Jones RJ, Horowitz MM, Mattila D, Saber W, Hamadani M, Martens MJ. Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-of-Life Evaluation and 2-Year Outcomes of BMT CTN 1703. J Clin Oncol. 2025 Mar 10;43(8):912-918. doi: 10.1200/JCO.24.00921. Epub 2025 Jan 3.

Drugs

Indications