Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Summary

The study is designed with drugs used frequently in the treatment of AML, but with a new combination less toxic,and effective in AML multidrug resistant. Justification: * The AML patients with primary resistance or relapsed in the first 12 months after CR, have second line chemotherapy low response rate . * These patients with AML with primary resistance or relapse, that reach remission after a rescue treatment, have an interval free survival and a global survival very short * Probably the resistance to the treatments is in relation to different forms expression of the MDR. * Complete remission is considered valid evaluation, because every patient who should obtain a CR can be considered to be eligible for a possible curative treatment: Ara-C administration to high doses or the TPH treatment

Timeline

Start

2003-05

Primary completion

—

Completion

2007-04

Publications

• Background Bishop JF. The treatment of adult acute myeloid leukemia. Semin Oncol. 1997 Feb;24(1):57-69.
• Background Stone RM. Treatment of acute myeloid leukemia: state-of-the-art and future directions. Semin Hematol. 2002 Jul;39(3 Suppl 2):4-10. doi: 10.1053/shem.2002.35977.
• Background Lister TA, Rohatiner AZ. The treatment of acute myelogenous leukemia in adults. Semin Hematol. 1982 Jul;19(3):172-92.
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• Background Rees JK, Gray RG, Swirsky D, Hayhoe FG. Principal results of the Medical Research Council's 8th acute myeloid leukaemia trial. Lancet. 1986 Nov 29;2(8518):1236-41. doi: 10.1016/s0140-6736(86)92674-7.
• Background Vey N, Keating M, Giles F, Cortes J, Beran M, Estey E. Effect of complete remission on survival in patients with acute myelogenous leukemia receiving first salvage therapy. Blood. 1999 May 1;93(9):3149-50. No abstract available.
• Background Del Poeta G, Venditti A, Aronica G, Stasi R, Cox MC, Buccisano F, Bruno A, Tamburini A, Suppo G, Simone MD, Epiceno AM, Del Moro B, Masi M, Papa G, Amadori S. P-glycoprotein expression in de novo acute myeloid leukemia. Leuk Lymphoma. 1997 Oct;27(3-4):257-74. doi: 10.3109/10428199709059682.
• Background Germann UA. P-glycoprotein--a mediator of multidrug resistance in tumour cells. Eur J Cancer. 1996 Jun;32A(6):927-44. doi: 10.1016/0959-8049(96)00057-3. No abstract available.
• Background Keating MJ, Kantarjian H, Smith TL, Estey E, Walters R, Andersson B, Beran M, McCredie KB, Freireich EJ. Response to salvage therapy and survival after relapse in acute myelogenous leukemia. J Clin Oncol. 1989 Aug;7(8):1071-80. doi: 10.1200/JCO.1989.7.8.1071.
• Background Nussler V, Pelka-Fleischer R, Zwierzina H, Nerl C, Beckert B, Gieseler F, Diem H, Ledderose G, Gullis E, Sauer H, Wilmanns W. P-glycoprotein expression in patients with acute leukemia-clinical relevance. Leukemia. 1996 Jul;10 Suppl 3:S23-S31.
• Background Hendricks CB, Rowinsky EK, Grochow LB, Donehower RC, Kaufmann SH. Effect of P-glycoprotein expression on the accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analogue. Cancer Res. 1992 Apr 15;52(8):2268-78.
• Background Michelutti A, Michieli M, Damiani D, Melli C, Ermacora A, Grimaz S, Candoni A, Russo D, Fanin R, Baccarani M. Effect of fludarabine and arabinosylcytosine on multidrug resistant cells. Haematologica. 1997 Mar-Apr;82(2):143-7.
• Background Leoni F, Ciolli S, Nozzoli C, Santini V, Fanci R, Rossi Ferrini P. Fludarabine, cytarabine and topotecan (FLAT) as induction therapy for acute myeloid leukemia in the elderly: a preliminary report. Haematologica. 2001 Jan;86(1):104. No abstract available.
• Background Frewin RJ, Johnson SA. The role of purine analogue combinations in the management of acute leukemias. Hematol Oncol. 2001 Dec;19(4):151-7. doi: 10.1002/hon.686.
• Background Seiter K, Feldman EJ, Halicka HD, Traganos F, Darzynkiewicz Z, Lake D, Ahmed T. Phase I clinical and laboratory evaluation of topotecan and cytarabine in patients with acute leukemia. J Clin Oncol. 1997 Jan;15(1):44-51. doi: 10.1200/JCO.1997.15.1.44.
• Background Sierra J, Brunet S, Granena A, Olive T, Bueno J, Ribera JM, Petit J, Besses C, Llorente A, Guardia R, Macia J, Rovira M, Badell I, Vela E, Diaz de Heredia C, Vivancos P, Carreras E, Feliu E, Montserrat E, Julia A, Cubells J, Rozman C, Domingo A, Ortega JJ. Feasibility and results of bone marrow transplantation after remission induction and intensification chemotherapy in de novo acute myeloid leukemia. Catalan Group for Bone Marrow Transplantation. J Clin Oncol. 1996 Apr;14(4):1353-63. doi: 10.1200/JCO.1996.14.4.1353.
• Background Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med. 1994 Oct 6;331(14):896-903. doi: 10.1056/NEJM199410063311402.
• Background Bennett CL, Smith TJ, Weeks JC, Bredt AB, Feinglass J, Fetting JH, Hillner BE, Somerfield MR, Winn RJ. Use of hematopoietic colony-stimulating factors: the American Society of Clinical Oncology survey. The Health Services Research Committee of the American Society of Clinical Oncology. J Clin Oncol. 1996 Sep;14(9):2511-20. doi: 10.1200/JCO.1996.14.9.2511.

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