A Phase Ib Study of ISF35 in Combination With Chemotherapy (FCR) in Subjects With Relapsed, Refractory, and/or 17p- CLL

Summary

The study is a Phase 1b open label, non-randomized, single institution clinical trial that is designed to evaluate the safety and tolerability of three repeat infusions of ISF35 followed by a standard regimen of three cycles of fludarabine, cyclophosphamide and rituximab (FCR) in subjects with refractory, resistant, and/or 17p- CLL.

Timeline

Start

2008-09

Primary completion

2011-04

Completion

2013-04

Publications

• Background Keating MJ, O'Brien S, Albitar M, Lerner S, Plunkett W, Giles F, Andreeff M, Cortes J, Faderl S, Thomas D, Koller C, Wierda W, Detry MA, Lynn A, Kantarjian H. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 2005 Jun 20;23(18):4079-88. doi: 10.1200/JCO.2005.12.051. Epub 2005 Mar 14.
• Background Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008 Jun 15;111(12):5446-56. doi: 10.1182/blood-2007-06-093906. Epub 2008 Jan 23.
• Background Rai KR. Characteristics and Management of Chronic Lymphocytic Leukemia. Advances in Oncology. 1996;9 No.1:17-20.
• Background Kalil N, Cheson BD. Chronic lymphocytic leukemia. Oncologist. 1999;4(5):352-69.
• Background Kay NE, Hamblin TJ, Jelinek DF, Dewald GW, Byrd JC, Farag S, Lucas M, Lin T. Chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2002:193-213. doi: 10.1182/asheducation-2002.1.193.
• Background Bosch F, Montserrat E. Refining prognostic factors in chronic lymphocytic leukemia. Rev Clin Exp Hematol. 2002 Dec;6(4):335-49; discussion 449-50. doi: 10.1046/j.1468-0734.2002.00302.x. No abstract available.
• Background Byrd JC, Waselenko JK, Keating M, Rai K, Grever MR. Novel therapies for chronic lymphocytic leukemia in the 21st century. Semin Oncol. 2000 Oct;27(5):587-97.
• Background Nabhan C, Gartenhaus RB, Tallman MS. Purine nucleoside analogues and combination therapies in B-cell chronic lymphocytic leukemia: dawn of a new era. Leuk Res. 2004 May;28(5):429-42. doi: 10.1016/j.leukres.2003.08.017.
• Background Nabhan C, Dyer MJ, Rosen ST. Current status of monoclonal antibody therapy for chronic lymphocytic leukemia. Oncology (Williston Park). 2003 Feb;17(2):253-62; discussion 264, 267, passim.
• Background Byrd JC, Stilgenbauer S, Flinn IW. Chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2004:163-83. doi: 10.1182/asheducation-2004.1.163.
• Background Rozman C, Montserrat E. Chronic lymphocytic leukemia. N Engl J Med. 1995 Oct 19;333(16):1052-7. doi: 10.1056/NEJM199510193331606. No abstract available.
• Background Ghia P, Caligaris-Cappio F. The origin of B-cell chronic lymphocytic leukemia. Semin Oncol. 2006 Apr;33(2):150-6. doi: 10.1053/j.seminoncol.2006.01.009.
• Background Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. 2005 Feb 24;352(8):804-15. doi: 10.1056/NEJMra041720. No abstract available.
• Background Perz J, Topaly J, Fruehauf S, Hensel M, Ho AD. Level of CD 20-expression and efficacy of rituximab treatment in patients with resistant or relapsing B-cell prolymphocytic leukemia and B-cell chronic lymphocytic leukemia. Leuk Lymphoma. 2002 Jan;43(1):149-51. doi: 10.1080/10428190210178.
• Background Cheson BD, Bennett JM, Rai KR, Grever MR, Kay NE, Schiffer CA, Oken MM, Keating MJ, Boldt DH, Kempin SJ, et al. Guidelines for clinical protocols for chronic lymphocytic leukemia: recommendations of the National Cancer Institute-sponsored working group. Am J Hematol. 1988 Nov;29(3):152-63. doi: 10.1002/ajh.2830290307.
• Background Lin TS, Lucas MS, Byrd JC. Rituximab in B-cell chronic lymphocytic leukemia. Semin Oncol. 2003 Aug;30(4):483-92. doi: 10.1016/s0093-7754(03)00239-2.
• Background O'Brien SM, Kantarjian H, Thomas DA, Giles FJ, Freireich EJ, Cortes J, Lerner S, Keating MJ. Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol. 2001 Apr 15;19(8):2165-70. doi: 10.1200/JCO.2001.19.8.2165.
• Background Byrd JC, Rai K, Peterson BL, Appelbaum FR, Morrison VA, Kolitz JE, Shepherd L, Hines JD, Schiffer CA, Larson RA. Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011. Blood. 2005 Jan 1;105(1):49-53. doi: 10.1182/blood-2004-03-0796. Epub 2004 May 11.
• Background Wierda W, O'Brien S, Wen S, Faderl S, Garcia-Manero G, Thomas D, Do KA, Cortes J, Koller C, Beran M, Ferrajoli A, Giles F, Lerner S, Albitar M, Kantarjian H, Keating M. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol. 2005 Jun 20;23(18):4070-8. doi: 10.1200/JCO.2005.12.516. Epub 2005 Mar 14.
• Background Kipps TJ. Chronic lymphocytic leukemia and related diseases. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, eds. Williams Hematology (ed 6). New York: McGraw-Hill, Inc.; 2001:1163-1194.
• Background Wierda WG, Cantwell MJ, Woods SJ, Rassenti LZ, Prussak CE, Kipps TJ. CD40-ligand (CD154) gene therapy for chronic lymphocytic leukemia. Blood. 2000 Nov 1;96(9):2917-24.
• Background Dicker F, Kater AP, Fukuda T, Kipps TJ. Fas-ligand (CD178) and TRAIL synergistically induce apoptosis of CD40-activated chronic lymphocytic leukemia B cells. Blood. 2005 Apr 15;105(8):3193-8. doi: 10.1182/blood-2003-10-3684. Epub 2004 Aug 31.
• Background Chu P, Deforce D, Pedersen IM, Kim Y, Kitada S, Reed JC, Kipps TJ. Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3854-9. doi: 10.1073/pnas.022604399. Epub 2002 Mar 12.
• Background Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L, Dohner K, Bentz M, Lichter P. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 28;343(26):1910-6. doi: 10.1056/NEJM200012283432602.
• Background Cantwell MJ, Sharma S, Friedmann T, Kipps TJ. Adenovirus vector infection of chronic lymphocytic leukemia B cells. Blood. 1996 Dec 15;88(12):4676-83.

Drugs

Indications