Fludarabine / Total Body Irradiation Regimen for ALLO HCT in Acute Lymphoblastic Leukemia

Summary

The goal of this research is to test if the conditioning regimen, fludarabine and total body irradiation (FluTBI), can lead to a safer and more effective stem cell transplant treatment regimen for ALL patients older than 40 years of age and/or younger patients with high risk medical conditions. The primary objective is to establish the efficacy of allo HCT in older ALL patients using myeloablative FluTBI conditioning regimen. The investigators are also assessing the safety and toxicity of allo HCT in older ALL patients using myeloablative FluTBI conditioning regimen.

Timeline

Start

2013-08-27

Primary completion

2020-01-30

Completion

2022-08-23

Publications

• Background Gaynon PS, Angiolillo AL, Carroll WL, Nachman JB, Trigg ME, Sather HN, Hunger SP, Devidas M; Children's Oncology Group. Long-term results of the children's cancer group studies for childhood acute lymphoblastic leukemia 1983-2002: a Children's Oncology Group Report. Leukemia. 2010 Feb;24(2):285-97. doi: 10.1038/leu.2009.262. Epub 2009 Dec 17.
• Background Annino L, Vegna ML, Camera A, Specchia G, Visani G, Fioritoni G, Ferrara F, Peta A, Ciolli S, Deplano W, Fabbiano F, Sica S, Di Raimondo F, Cascavilla N, Tabilio A, Leoni P, Invernizzi R, Baccarani M, Rotoli B, Amadori S, Mandelli F; GIMEMA Group. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood. 2002 Feb 1;99(3):863-71. doi: 10.1182/blood.v99.3.863.
• Background Alvarnas JC, Brown PA, Aoun P, Ballen KK, Bellam N, Blum W, Boyer MW, Carraway HE, Coccia PF, Coutre SE, Cultrera J, Damon LE, DeAngelo DJ, Douer D, Frangoul H, Frankfurt O, Goorha S, Millenson MM, O'Brien S, Petersdorf SH, Rao AV, Terezakis S, Uy G, Wetzler M, Zelenetz AD, Naganuma M, Gregory KM; National Comprehensive Cancer Network. Acute lymphoblastic leukemia. J Natl Compr Canc Netw. 2012 Jul 1;10(7):858-914. doi: 10.6004/jnccn.2012.0089.
• Background Larson RA, Dodge RK, Burns CP, Lee EJ, Stone RM, Schulman P, Duggan D, Davey FR, Sobol RE, Frankel SR, et al. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood. 1995 Apr 15;85(8):2025-37.
• Background Yanada M, Matsuo K, Suzuki T, Naoe T. Allogeneic hematopoietic stem cell transplantation as part of postremission therapy improves survival for adult patients with high-risk acute lymphoblastic leukemia: a metaanalysis. Cancer. 2006 Jun 15;106(12):2657-63. doi: 10.1002/cncr.21932.
• Background Bachanova V, Weisdorf D. Unrelated donor allogeneic transplantation for adult acute lymphoblastic leukemia: a review. Bone Marrow Transplant. 2008 Mar;41(5):455-64. doi: 10.1038/sj.bmt.1705889. Epub 2007 Oct 29.
• Background Hahn T, Wall D, Camitta B, Davies S, Dillon H, Gaynon P, Larson RA, Parsons S, Seidenfeld J, Weisdorf D, McCarthy PL Jr. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in adults: an evidence-based review. Biol Blood Marrow Transplant. 2006 Jan;12(1):1-30. doi: 10.1016/j.bbmt.2005.10.018.
• Background Chaidos A, Kanfer E, Apperley JF. Risk assessment in haemotopoietic stem cell transplantation: disease and disease stage. Best Pract Res Clin Haematol. 2007 Jun;20(2):125-54. doi: 10.1016/j.beha.2006.10.003.
• Background Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. doi: 10.1182/blood-2007-10-116582. Epub 2007 Nov 29.
• Background Ringden O, Labopin M, Tura S, Arcese W, Iriondo A, Zittoun R, Sierra J, Gorin NC. A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol. 1996 Jun;93(3):637-45. doi: 10.1046/j.1365-2141.1996.d01-1681.x.
• Background Davies SM, Ramsay NK, Klein JP, Weisdorf DJ, Bolwell B, Cahn JY, Camitta BM, Gale RP, Giralt S, Heilmann C, Henslee-Downey PJ, Herzig RH, Hutchinson R, Keating A, Lazarus HM, Milone GA, Neudorf S, Perez WS, Powles RL, Prentice HG, Schiller G, Socie G, Vowels M, Wiley J, Yeager A, Horowitz MM. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol. 2000 Jan;18(2):340-7. doi: 10.1200/JCO.2000.18.2.340.
• Background Marks DI, Forman SJ, Blume KG, Perez WS, Weisdorf DJ, Keating A, Gale RP, Cairo MS, Copelan EA, Horan JT, Lazarus HM, Litzow MR, McCarthy PL, Schultz KR, Smith DD, Trigg ME, Zhang MJ, Horowitz MM. A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. Biol Blood Marrow Transplant. 2006 Apr;12(4):438-53. doi: 10.1016/j.bbmt.2005.12.029.
• Background Snyder DS, Nademanee AP, O'Donnell MR, Parker PM, Stein AS, Margolin K, Somlo G, Molina A, Spielberger R, Kashyap A, Fung H, Slovak ML, Dagis A, Negrin RS, Amylon MD, Blume KG, Forman SJ. Long-term follow-up of 23 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic bone marrow transplant in first complete remission. Leukemia. 1999 Dec;13(12):2053-8. doi: 10.1038/sj.leu.2401589.
• Background Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, Rimm AA, Ringden O, Rozman C, Speck B, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990 Feb 1;75(3):555-62.
• Background Gale RP, Horowitz MM. Graft-versus-leukemia in bone marrow transplantation. The Advisory Committee of the International Bone Marrow Transplant Registry. Bone Marrow Transplant. 1990 Jul;6 Suppl 1:94-7.
• Background Arnold R, Massenkeil G, Bornhauser M, Ehninger G, Beelen DW, Fauser AA, Hegenbart U, Hertenstein B, Ho AD, Knauf W, Kolb HJ, Kolbe K, Sayer HG, Schwerdtfeger R, Wandt H, Hoelzer D. Nonmyeloablative stem cell transplantation in adults with high-risk ALL may be effective in early but not in advanced disease. Leukemia. 2002 Dec;16(12):2423-8. doi: 10.1038/sj.leu.2402712.
• Background Martino R, Giralt S, Caballero MD, Mackinnon S, Corradini P, Fernandez-Aviles F, San Miguel J, Sierra J. Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning in acute lymphoblastic leukemia: a feasibility study. Haematologica. 2003 May;88(5):555-60.
• Background Hamaki T, Kami M, Kanda Y, Yuji K, Inamoto Y, Kishi Y, Nakai K, Nakayama I, Murashige N, Abe Y, Ueda Y, Hino M, Inoue T, Ago H, Hidaka M, Hayashi T, Yamane T, Uoshima N, Miyakoshi S, Taniguchi S. Reduced-intensity stem-cell transplantation for adult acute lymphoblastic leukemia: a retrospective study of 33 patients. Bone Marrow Transplant. 2005 Mar;35(6):549-56. doi: 10.1038/sj.bmt.1704776.
• Background Gutierrez-Aguirre CH, Gomez-Almaguer D, Cantu-Rodriguez OG, Gonzalez-Llano O, Jaime-Perez JC, Herena-Perez S, Manzano CA, Estrada-Gomez R, Gonzalez-Carrillo ML, Ruiz-Arguelles GJ. Non-myeloablative stem cell transplantation in patients with relapsed acute lymphoblastic leukemia: results of a multicenter study. Bone Marrow Transplant. 2007 Sep;40(6):535-9. doi: 10.1038/sj.bmt.1705769. Epub 2007 Jul 9.
• Background Mohty M, Labopin M, Tabrizzi R, Theorin N, Fauser AA, Rambaldi A, Maertens J, Slavin S, Majolino I, Nagler A, Blaise D, Rocha V; Acute Leukemia Working Party; European Group for Blood and Marrow Transplantation. Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation. Haematologica. 2008 Feb;93(2):303-6. doi: 10.3324/haematol.11960.
• Background Devine SM, Sanborn R, Jessop E, Stock W, Huml M, Peace D, Wickrema A, Yassine M, Amin K, Thomason D, Chen YH, Devine H, Maningo M, van Besien K. Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant. Bone Marrow Transplant. 2001 Sep;28(6):557-62. doi: 10.1038/sj.bmt.1703198.
• Background Ciurea SO, Saliba RM, Hamerschlak N, Karduss Aurueta AJ, Bassett R, Fernandez-Vina M, Petropoulos D, Worth LL, Chan KW, Couriel DR, Rondon G, Sharma M, Qazilbash M, Jones RB, Kebriaei P, McMannis J, Hosing CM, Nieto Y, Champlin RE, Shpall EJ, de Lima M. Fludarabine, melphalan, thiotepa and anti-thymocyte globulin conditioning for unrelated cord blood transplant. Leuk Lymphoma. 2012 May;53(5):901-6. doi: 10.3109/10428194.2011.631159. Epub 2012 Jan 3.
• Background Ram R, Storb R, Sandmaier BM, Maloney DG, Woolfrey A, Flowers ME, Maris MB, Laport GG, Chauncey TR, Lange T, Langston AA, Storer B, Georges GE. Non-myeloablative conditioning with allogeneic hematopoietic cell transplantation for the treatment of high-risk acute lymphoblastic leukemia. Haematologica. 2011 Aug;96(8):1113-20. doi: 10.3324/haematol.2011.040261. Epub 2011 Apr 20.
• Background Alousi A, de Lima M. Reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation. Clin Adv Hematol Oncol. 2007 Jul;5(7):560-70.
• Background Kroger N, Bornhauser M, Ehninger G, Schwerdtfeger R, Biersack H, Sayer HG, Wandt H, Schafer-Eckardt K, Beyer J, Kiehl M, Zander AR; German Cooperative Transplant Study Group. Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. Ann Hematol. 2003 Jun;82(6):336-42. doi: 10.1007/s00277-003-0654-9. Epub 2003 May 1.
• Background Stelljes M, Bornhauser M, Kroger M, Beyer J, Sauerland MC, Heinecke A, Berning B, Scheffold C, Silling G, Buchner T, Neubauer A, Fauser AA, Ehninger G, Berdel WE, Kienast J; Cooperative German Transplant Study Group. Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia. Blood. 2005 Nov 1;106(9):3314-21. doi: 10.1182/blood-2005-04-1377. Epub 2005 Jul 14.
• Background Nakamura Y, Mori T, Kato J, Aisa Y, Nakazato T, Shigematsu N, Okamoto S. [Allogeneic hematopoietic stem cell transplantation with fludarabine, melphalan, and total body irradiation as a conditioning for elderly patients with myeloid malignancies]. Rinsho Ketsueki. 2012 Mar;53(3):318-22. Japanese.
• 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 Fiere D, Lepage E, Sebban C, Boucheix C, Gisselbrecht C, Vernant JP, Varet B, Broustet A, Cahn JY, Rigal-Huguet F, et al. Adult acute lymphoblastic leukemia: a multicentric randomized trial testing bone marrow transplantation as postremission therapy. The French Group on Therapy for Adult Acute Lymphoblastic Leukemia. J Clin Oncol. 1993 Oct;11(10):1990-2001. doi: 10.1200/JCO.1993.11.10.1990.
• Background Sebban C, Lepage E, Vernant JP, Gluckman E, Attal M, Reiffers J, Sutton L, Racadot E, Michallet M, Maraninchi D, et al. Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. French Group of Therapy of Adult Acute Lymphoblastic Leukemia. J Clin Oncol. 1994 Dec;12(12):2580-7. doi: 10.1200/JCO.1994.12.12.2580.

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Indications