Study of MK 2206 in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma

Summary

The purpose of this study is to evaluate the antitumor efficacy and the safety of MK 2206 in patients with relapsed or refractory diffuse large B cell lymphoma.

Timeline

Start

2011-11

Primary completion

2013-09

Completion

2014-06

Publications

• Background Thieblemont C, Gisselbrecht C. Second-line treatment paradigms for diffuse large B-cell lymphomas. Curr Oncol Rep. 2009 Sep;11(5):386-93. doi: 10.1007/s11912-009-0052-0.
• Background Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. doi: 10.1056/NEJM199512073332305.
• Background Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Briere J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. doi: 10.1200/JCO.2010.28.1618. Epub 2010 Jul 26.
• Background Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. doi: 10.1200/JCO.2005.09.131. Epub 2005 May 2.
• Background Lignon J, Sibon D, Madelaine I, Brice P, Franchi P, Briere J, Mounier N, Gisselbrecht C, Faure P, Thieblemont C. Rituximab, dexamethasone, cytarabine, and oxaliplatin (R-DHAX) is an effective and safe salvage regimen in relapsed/refractory B-cell non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk. 2010 Aug;10(4):262-9. doi: 10.3816/CLML.2010.n.055.
• Background Coiffier B. Fourteen years of high-dose CHOP (ACVB regimen): preliminary conclusions about the treatment of aggressive-lymphoma patients. Hamilton Fairley Award Lecture, European Society for Medical Oncology Meeting, Lisbon, November 21, 1994. Ann Oncol. 1995 Mar;6(3):211-7. doi: 10.1093/oxfordjournals.annonc.a059149. No abstract available.
• Background Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. doi: 10.1200/JCO.2007.13.1391. Epub 2008 Mar 31.
• Background Dupuis J, Itti E, Rahmouni A, Hemery F, Gisselbrecht C, Lin C, Copie-Bergman C, Belhadj K, El Gnaoui T, Gaillard I, Kuhnowski F, Meignan M, Haioun C. Response assessment after an inductive CHOP or CHOP-like regimen with or without rituximab in 103 patients with diffuse large B-cell lymphoma: integrating 18fluorodeoxyglucose positron emission tomography to the International Workshop Criteria. Ann Oncol. 2009 Mar;20(3):503-7. doi: 10.1093/annonc/mdn671. Epub 2008 Dec 11.
• Background Shipp MA. Molecular signatures define new rational treatment targets in large B-cell lymphomas. Hematology Am Soc Hematol Educ Program. 2007:265-9. doi: 10.1182/asheducation-2007.1.265.
• Background Altomare DA, Testa JR. Perturbations of the AKT signaling pathway in human cancer. Oncogene. 2005 Nov 14;24(50):7455-64. doi: 10.1038/sj.onc.1209085.
• Background Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov. 2005 Dec;4(12):988-1004. doi: 10.1038/nrd1902.
• Background Steelman LS, Stadelman KM, Chappell WH, Horn S, Basecke J, Cervello M, Nicoletti F, Libra M, Stivala F, Martelli AM, McCubrey JA. Akt as a therapeutic target in cancer. Expert Opin Ther Targets. 2008 Sep;12(9):1139-65. doi: 10.1517/14728222.12.9.1139.
• Background Sarbassov DD, Ali SM, Sabatini DM. Growing roles for the mTOR pathway. Curr Opin Cell Biol. 2005 Dec;17(6):596-603. doi: 10.1016/j.ceb.2005.09.009. Epub 2005 Oct 13.
• Background Gupta M, Ansell SM, Novak AJ, Kumar S, Kaufmann SH, Witzig TE. Inhibition of histone deacetylase overcomes rapamycin-mediated resistance in diffuse large B-cell lymphoma by inhibiting Akt signaling through mTORC2. Blood. 2009 Oct 1;114(14):2926-35. doi: 10.1182/blood-2009-05-220889. Epub 2009 Jul 29.
• Background Hay N. The Akt-mTOR tango and its relevance to cancer. Cancer Cell. 2005 Sep;8(3):179-83. doi: 10.1016/j.ccr.2005.08.008.
• Background Weil RJ. Incorporating molecular tools into early-stage clinical trials. PLoS Med. 2008 Jan 22;5(1):e21. doi: 10.1371/journal.pmed.0050021.
• Background Kawauchi K, Ogasawara T, Yasuyama M, Otsuka K, Yamada O. The PI3K/Akt pathway as a target in the treatment of hematologic malignancies. Anticancer Agents Med Chem. 2009 Jun;9(5):550-9. doi: 10.2174/187152009788451851.
• Background Testa JR, Bellacosa A. AKT plays a central role in tumorigenesis. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):10983-5. doi: 10.1073/pnas.211430998. No abstract available.
• Background Hasselblom S, Hansson U, Olsson M, Toren L, Bergstrom A, Nilsson-Ehle H, Andersson PO. High immunohistochemical expression of p-AKT predicts inferior survival in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Br J Haematol. 2010 May;149(4):560-8. doi: 10.1111/j.1365-2141.2010.08123.x. Epub 2010 Mar 1.
• Background Uddin S, Hussain AR, Siraj AK, Manogaran PS, Al-Jomah NA, Moorji A, Atizado V, Al-Dayel F, Belgaumi A, El-Solh H, Ezzat A, Bavi P, Al-Kuraya KS. Role of phosphatidylinositol 3'-kinase/AKT pathway in diffuse large B-cell lymphoma survival. Blood. 2006 Dec 15;108(13):4178-86. doi: 10.1182/blood-2006-04-016907. Epub 2006 Aug 31.
• Background Wanner K, Hipp S, Oelsner M, Ringshausen I, Bogner C, Peschel C, Decker T. Mammalian target of rapamycin inhibition induces cell cycle arrest in diffuse large B cell lymphoma (DLBCL) cells and sensitises DLBCL cells to rituximab. Br J Haematol. 2006 Sep;134(5):475-84. doi: 10.1111/j.1365-2141.2006.06210.x.
• Background Reeder CB, Gornet MK, Habermann TM, et al.: A phase II trial of the oral mTOR inhibitor Everolimus (RAD001) in relapsed aggressive Non-Hodgkin Lymphoma (NHL), in (ed 110; Abstract 121), 2007
• Background Johnson PB, Ansell SM, Colgan JP, et al.: Phase II trial of the oral mTOR inhibitor everolimus (RAD001) for patients with relapsed or refractory lymphoma, in (ed 25, No. 18S, Abstract 8055), 2007
• Background Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. doi: 10.1200/JCO.2010.29.2813. Epub 2010 Sep 13.
• Background Woehrer S, Hejna M, Skrabs C, Drach J, Zielinski CC, Jaeger U, Raderer M. Rituximab, Ara-C, dexamethasone and oxaliplatin is safe and active in heavily pretreated patients with diffuse large B-cell lymphoma. Oncology. 2005;69(6):499-502. doi: 10.1159/000091031. Epub 2006 Jan 16.
• Background Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008 Oct 20;26(30):4952-7. doi: 10.1200/JCO.2007.15.3429. Epub 2008 Jul 7.
• Background Goy A, Younes A, McLaughlin P, Pro B, Romaguera JE, Hagemeister F, Fayad L, Dang NH, Samaniego F, Wang M, Broglio K, Samuels B, Gilles F, Sarris AH, Hart S, Trehu E, Schenkein D, Cabanillas F, Rodriguez AM. Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2005 Feb 1;23(4):667-75. doi: 10.1200/JCO.2005.03.108. Epub 2004 Dec 21.
• Background Robertson MJ, Kahl BS, Vose JM, de Vos S, Laughlin M, Flynn PJ, Rowland K, Cruz JC, Goldberg SL, Musib L, Darstein C, Enas N, Kutok JL, Aster JC, Neuberg D, Savage KJ, LaCasce A, Thornton D, Slapak CA, Shipp MA. Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2007 May 1;25(13):1741-6. doi: 10.1200/JCO.2006.09.3146. Epub 2007 Mar 26.
• Background Casasnovas RO, Meignan M, Berriolo-Riedinger A, Bardet S, Julian A, Thieblemont C, Vera P, Bologna S, Briere J, Jais JP, Haioun C, Coiffier B, Morschhauser F; Groupe d'etude des lymphomes de l'adulte (GELA). SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma. Blood. 2011 Jul 7;118(1):37-43. doi: 10.1182/blood-2010-12-327767. Epub 2011 Apr 25.
• Background Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, Wiseman GA, Kostakoglu L, Scheidhauer K, Buck A, Naumann R, Spaepen K, Hicks RJ, Weber WA, Reske SN, Schwaiger M, Schwartz LH, Zijlstra JM, Siegel BA, Cheson BD; Imaging Subcommittee of International Harmonization Project in Lymphoma. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007 Feb 10;25(5):571-8. doi: 10.1200/JCO.2006.08.2305. Epub 2007 Jan 22.
• Background Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. doi: 10.1200/JCO.1999.17.4.1244.
• Background Meignan M, Itti E, Gallamini A, Haioun C. Interim 18F-fluorodeoxyglucose positron emission tomography in diffuse large B-cell lymphoma: qualitative or quantitative interpretation--where do we stand? Leuk Lymphoma. 2009 Nov;50(11):1753-6. doi: 10.3109/10428190903308056.
• Background Meignan M, Gallamini A, Haioun C, Polliack A. Report on the Second International Workshop on interim positron emission tomography in lymphoma held in Menton, France, 8-9 April 2010. Leuk Lymphoma. 2010 Dec;51(12):2171-80. doi: 10.3109/10428194.2010.529208. Epub 2010 Nov 15.

Drugs

Indications