Selinexor Combined With R-GemOx as Second-line Treatment in Patients With Diffuse Large B-cell Lymphoma

Summary

The goal of this interventional study is to evaluate efficiency and safety in prior one-line treated diffuse large B-cell lymphoma. The main questions it aims to answer are: * Complete remission rate * Objective remission rate * Progression-free survival * tolerance Participants will recevied a minimum of 2 and a maximum of 6 cycles of R-GemOx(rituximab 375 mg/m2 IV on day 1 , Gemcitabine 1000 mg/m2, Oxaliplatin 100 mg/m2 IV on day 2) and 60 mg selinexor on days 1, 8, and 15 of each cycle

Timeline

Start

2023-02-28

Primary completion

2024-03-31

Completion

2024-09-30

Publications

• Results Krok-Schoen JL, Fisher JL, Stephens JA, Mims A, Ayyappan S, Woyach JA, Rosko AE. Incidence and survival of hematological cancers among adults ages >/=75 years. Cancer Med. 2018 Jul;7(7):3425-3433. doi: 10.1002/cam4.1461. Epub 2018 Apr 13.
• Results Harris LJ, Patel K, Martin M. Novel Therapies for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Int J Mol Sci. 2020 Nov 13;21(22):8553. doi: 10.3390/ijms21228553.
• Results Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808. Blood. 2018 Feb 1;131(5):587-588. doi: 10.1182/blood-2017-11-817775. No abstract available.
• Results Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, Lopez-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. doi: 10.1016/S1470-2045(06)70664-7.
• Results Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. doi: 10.1016/S0140-6736(13)60313-X. Epub 2013 Apr 22.
• Results Arboe B, Olsen MH, Gorlov JS, Duun-Henriksen AK, Dalton SO, Johansen C, de Nully Brown P. Treatment intensity and survival in patients with relapsed or refractory diffuse large B-cell lymphoma in Denmark: a real-life population-based study. Clin Epidemiol. 2019 Mar 4;11:207-216. doi: 10.2147/CLEP.S178003. eCollection 2019.
• Results 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.
• Results 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.
• Results Mounier N, El Gnaoui T, Tilly H, Canioni D, Sebban C, Casasnovas RO, Delarue R, Sonet A, Beaussart P, Petrella T, Castaigne S, Bologna S, Salles G, Rahmouni A, Gaulard P, Haioun C. Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial. Haematologica. 2013 Nov;98(11):1726-31. doi: 10.3324/haematol.2013.090597. Epub 2013 Jun 10.
• Results Corazzelli G, Capobianco G, Arcamone M, Ballerini PF, Iannitto E, Russo F, Frigeri F, Becchimanzi C, Marcacci G, De Chiara A, Pinto A. Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma. Cancer Chemother Pharmacol. 2009 Oct;64(5):907-16. doi: 10.1007/s00280-009-0941-9. Epub 2009 Feb 15.
• Results Cazelles C, Belhadj K, Vellemans H, Camus V, Poullot E, Gaulard P, Veresezan L, Itti E, Becker S, Carvalho M, Dupuis J, Le Bras F, Lemonnier F, Roulin L, El Gnaoui T, Jardin F, Mounier N, Tilly H, Haioun C. Rituximab plus gemcitabine and oxaliplatin (R-GemOx) in refractory/relapsed diffuse large B-cell lymphoma: a real-life study in patients ineligible for autologous stem-cell transplantation. Leuk Lymphoma. 2021 Sep;62(9):2161-2168. doi: 10.1080/10428194.2021.1901090. Epub 2021 Mar 25.
• Results Azizian NG, Li Y. XPO1-dependent nuclear export as a target for cancer therapy. J Hematol Oncol. 2020 Jun 1;13(1):61. doi: 10.1186/s13045-020-00903-4.
• Results Gandhi UH, Senapedis W, Baloglu E, Unger TJ, Chari A, Vogl D, Cornell RF. Clinical Implications of Targeting XPO1-mediated Nuclear Export in Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2018 May;18(5):335-345. doi: 10.1016/j.clml.2018.03.003. Epub 2018 Mar 14.
• Results Deng M, Zhang M, Xu-Monette ZY, Pham LV, Tzankov A, Visco C, Fang X, Bhagat G, Zhu F, Dybkaer K, Chiu A, Tam W, Zu Y, Hsi ED, Choi WWL, Huh J, Ponzoni M, Ferreri AJM, Moller MB, Parsons BM, van Krieken JH, Piris MA, Winter JN, Hagemeister F, Alinari L, Li Y, Andreeff M, Xu B, Young KH. XPO1 expression worsens the prognosis of unfavorable DLBCL that can be effectively targeted by selinexor in the absence of mutant p53. J Hematol Oncol. 2020 Nov 4;13(1):148. doi: 10.1186/s13045-020-00982-3.
• Results Kalakonda N, Maerevoet M, Cavallo F, Follows G, Goy A, Vermaat JSP, Casasnovas O, Hamad N, Zijlstra JM, Bakhshi S, Bouabdallah R, Choquet S, Gurion R, Hill B, Jaeger U, Sancho JM, Schuster M, Thieblemont C, De la Cruz F, Egyed M, Mishra S, Offner F, Vassilakopoulos TP, Warzocha K, McCarthy D, Ma X, Corona K, Saint-Martin JR, Chang H, Landesman Y, Joshi A, Wang H, Shah J, Shacham S, Kauffman M, Van Den Neste E, Canales MA. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020 Jul;7(7):e511-e522. doi: 10.1016/S2352-3026(20)30120-4.
• Results Kazim S, Malafa MP, Coppola D, Husain K, Zibadi S, Kashyap T, Crochiere M, Landesman Y, Rashal T, Sullivan DM, Mahipal A. Selective Nuclear Export Inhibitor KPT-330 Enhances the Antitumor Activity of Gemcitabine in Human Pancreatic Cancer. Mol Cancer Ther. 2015 Jul;14(7):1570-81. doi: 10.1158/1535-7163.MCT-15-0104. Epub 2015 May 1.
• Results Corno C, Stucchi S, De Cesare M, Carenini N, Stamatakos S, Ciusani E, Minoli L, Scanziani E, Argueta C, Landesman Y, Zaffaroni N, Gatti L, Perego P. FoxO-1 contributes to the efficacy of the combination of the XPO1 inhibitor selinexor and cisplatin in ovarian carcinoma preclinical models. Biochem Pharmacol. 2018 Jan;147:93-103. doi: 10.1016/j.bcp.2017.11.009. Epub 2017 Nov 16.

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