Fludarabine and Intermediate-dose TBI Followed by PTCy in Patients Undergoing Allo Transplant for Heme Malignancies

Summary

The Flu-TBI 800 trial is a prospective, single-arm, multicenter, interventional phase 2 study to evaluate whether fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy) (experimental regimen) improves the 1-year survival of allogeneic stem cell transplant recipients.

Timeline

Start

2026-01-06

Primary completion

2032-01

Completion

2032-01

Publications

• Background Martens MJ, Lian Q, Geller NL, Leifer ES, Logan BR. Sequential monitoring of time-to-event safety endpoints in clinical trials. Clin Trials. 2025 Jun;22(3):267-278. doi: 10.1177/17407745241304119. Epub 2024 Dec 29.
• Background Wu J, Chen L, Wei J, Weiss H, Chauhan A. Two-stage phase II survival trial design. Pharm Stat. 2020 May;19(3):214-229. doi: 10.1002/pst.1983. Epub 2019 Nov 21.
• Background Mycophenolate REMS (Risk Evaluation and Mitigation Strategy). https://www.accessdata.fda.gov
• Background Vaxman I, Muchtar E, Jacob E, Kapoor P, Kumar S, Dispenzieri A, Buadi F, Dingli D, Gonsalves W, Kourelis T, Warsame R, Lacy M, Hogan W, Gertz MA. The Efficacy and Safety of Chemotherapy-Based Stem Cell Mobilization in Multiple Myeloma Patients Who Are Poor Responders to Induction: The Mayo Clinic Experience. Transplant Cell Ther. 2021 Sep;27(9):770.e1-770.e7. doi: 10.1016/j.jtct.2021.06.016. Epub 2021 Jun 18.
• Background Xhaard A, Rocha V, Bueno B, de Latour RP, Lenglet J, Petropoulou A, Rodriguez-Otero P, Ribaud P, Porcher R, Socie G, Robin M. Steroid-refractory acute GVHD: lack of long-term improved survival using new generation anticytokine treatment. Biol Blood Marrow Transplant. 2012 Mar;18(3):406-13. doi: 10.1016/j.bbmt.2011.06.012. Epub 2011 Jul 4.
• Background Sengsayadeth S, Wang T, Lee SJ, Haagenson MD, Spellman S, Fernandez Vina MA, Muller CR, Verneris MR, Savani BN, Jagasia M. Cytotoxic T-lymphocyte antigen-4 single nucleotide polymorphisms are not associated with outcomes after unrelated donor transplantation: a center for international blood and marrow transplant research analysis. Biol Blood Marrow Transplant. 2014 Jun;20(6):900-3. doi: 10.1016/j.bbmt.2014.03.005. Epub 2014 Mar 14.
• Background Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.
• Background Lee JW, Cho BS, Lee SE, Eom KS, Kim YJ, Kim HJ, Lee S, Min CK, Cho SG, Min WS, Park CW. The Outcome of Unrelated Hematopoietic Stem Cell Transplants with Total Body Irradiation (800 cGy) and Cyclophosphamide (120 mg/kg) in Adult Patients with Acquired Severe Aplastic Anemia. Biol Blood Marrow Transplant. 2011 Jan;17(1):101-8. doi: 10.1016/j.bbmt.2010.06.014. Epub 2010 Jun 25.
• Background Sanchez-Petitto G, Huang Y, Bezerra E, et al. Comparison of Two Myeloablative Total-Body Irradiation (MAC-TBI) Regimens: 1200 Cgy Vs 800 Cgy of TBI for Allogeneic Stem Cell Transplantation in Adults with Hematological Malignancies. Blood. 2024;144(Supplement 1):7303-7303. doi:10.1182/blood-2024-194146
• Background Sterling CH, Hughes MS, Tsai HL, et al. Non-myeloablative allogeneic blood or marrow transplantation (AlloBMT) with post-transplant cyclophosphamide (PTCy) for peripheral T- cell lymphoma (PTCL): Improved outcomes with peripheral blood (PB) allografts and increased total body irradiation (TBI) to 400 cGV. J Clin Oncol. 2022;40(16_suppl):7047- 7047. doi:10.1200/JCO.2022.40.16_suppl.7047
• Background Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, Martin PJ, Sandmaier BM, Marr KA, Appelbaum FR, Storb R, McDonald GB. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010 Nov 25;363(22):2091-101. doi: 10.1056/NEJMoa1004383.
• Background Ciurea S, Zhang M, Kanakry C. CNIs versus post-transplant cyclophosphamide-based GVHD prophylaxis in haploidentical transplantation. Blood. 2020;137(4):444-455.
• Background Kanakry CG, Tsai HL, Bolanos-Meade J, Smith BD, Gojo I, Kanakry JA, Kasamon YL, Gladstone DE, Matsui W, Borrello I, Huff CA, Swinnen LJ, Powell JD, Pratz KW, DeZern AE, Showel MM, McDevitt MA, Brodsky RA, Levis MJ, Ambinder RF, Fuchs EJ, Rosner GL, Jones RJ, Luznik L. Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS. Blood. 2014 Dec 11;124(25):3817-27. doi: 10.1182/blood-2014-07-587477. Epub 2014 Oct 14.
• 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.
• Background Luznik L, O'Donnell PV, Fuchs EJ. Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. Semin Oncol. 2012 Dec;39(6):683-93. doi: 10.1053/j.seminoncol.2012.09.005.
• Background Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. doi: 10.1200/JCO.2016.70.7091. Epub 2017 Feb 13.
• Background Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006 Apr 27;354(17):1813-26. doi: 10.1056/NEJMra052638. No abstract available.
• Background Baron F, Labopin M, Blaise D. Reduced-intensity conditioning versus myeloablative conditioning allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia: A study from the Acute Leukemia Working Party of the EBMT. Blood. 2017;129(4):448-456.
• Background Gyurkocza B, Rezvani A, Storb RF. Allogeneic hematopoietic cell transplantation: the state of the art. Expert Rev Hematol. 2010 Jun;3(3):285-99. doi: 10.1586/ehm.10.21.

Drugs

Indications