LINFOTARGAM: Treatment With Chemotherapy Plus Rituximab and Highly Active Antiretroviral Therapy in Patients With Diffuse Large B Cell Lymphoma and Infection With the Human Immunodeficiency Virus (HIV)

Summary

Main objective: * To evaluate the applicability of the treatment: 1. To evaluate the treatment toxicity according to the Common Terminology Criteria (CTC) version 3.0 of the National Cancer Institute (NCI). 2. To evaluate opportunistic and non-opportunistic infections after 6 cycles of treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) administered every 14 days and highly active antiretroviral therapy (HAART) in patients with diffuse large B cell lymphoma (DLBCL) and HIV infection. 3. To evaluate the adherence to the treatment with 6 cycles of R-CHOP considering the delays in the administration of the cycles and the reductions in the doses of chemotherapy (planned dose administered in predicted term). Secondary objectives: * To evaluate the efficacy of the treatment in patients with DLBCL and HIV infection after 6 cycles of treatment with R-CHOP administered every 14 days (R-CHOP/14): 1. To determine the global response and complete remission tax. 2. To evaluate the duration of the response. 3. To evaluate the probability of event-free survival in 5 years. 4. To evaluate the probability of global survival in 5 years. * To identify predictive factors of response after 6 cycles of treatment with R-CHOP administered every 14 days in patients with DLBCL and HIV infection. * To evaluate the impact of the therapeutic combination of R-CHOP and HAART in the parameters of the HIV infection (HIV viral load and CD4+ lymphocyte count).

Timeline

Start

2006-10

Primary completion

2009-05

Completion

2009-11

Publications

• Background Engels EA, Goedert JJ. Human immunodeficiency virus/acquired immunodeficiency syndrome and cancer: past, present, and future. J Natl Cancer Inst. 2005 Mar 16;97(6):407-9. doi: 10.1093/jnci/dji085. No abstract available.
• Background Noy A. Update in HIV-associated lymphoma. Curr Opin Oncol. 2004 Sep;16(5):450-4. doi: 10.1097/00001622-200409000-00007.
• Background Bonnet F, Lewden C, May T, Heripret L, Jougla E, Bevilacqua S, Costagliola D, Salmon D, Chene G, Morlat P. Malignancy-related causes of death in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy. Cancer. 2004 Jul 15;101(2):317-24. doi: 10.1002/cncr.20354.
• Background Carrieri MP, Pradier C, Piselli P, Piche M, Rosenthal E, Heudier P, Durant J, Serraino D. Reduced incidence of Kaposi's sarcoma and of systemic non-hodgkin's lymphoma in HIV-infected individuals treated with highly active antiretroviral therapy. Int J Cancer. 2003 Jan 1;103(1):142-4. doi: 10.1002/ijc.10790. No abstract available.
• Background Ribera JM, Navarro JT. [Lymphomas in patients with HIV infection. A change for the better]. Enferm Infecc Microbiol Clin. 2004 Jun-Jul;22(6):313-4. doi: 10.1157/13063040. No abstract available. Spanish.
• Background Hoffmann C, Chow KU, Wolf E, Faetkenheuer G, Stellbrink HJ, van Lunzen J, Jaeger H, Stoehr A, Plettenberg A, Wasmuth JC, Rockstroh J, Mosthaf F, Horst HA, Brodt HR. Strong impact of highly active antiretroviral therapy on survival in patients with human immunodeficiency virus-associated Hodgkin's disease. Br J Haematol. 2004 May;125(4):455-62. doi: 10.1111/j.1365-2141.2004.04934.x.
• Background Navarro JT, Lloveras N, Ribera JM, Oriol A, Mate JL, Feliu E. The prognosis of HIV-infected patients with diffuse large B-cell lymphoma treated with chemotherapy and highly active antiretroviral therapy is similar to that of HIV-negative patients receiving chemotherapy. Haematologica. 2005 May;90(5):704-6.
• Background Spina M, Carbone A, Vaccher E, Gloghini A, Talamini R, Cinelli R, Martellotta F, Tirelli U. Outcome in patients with non-hodgkin lymphoma and with or without human immunodeficiency virus infection. Clin Infect Dis. 2004 Jan 1;38(1):142-4. doi: 10.1086/380129. Epub 2003 Dec 5.
• Background J Berenguer, R Rubio, JM Ribera, A Antela, J Santos, P Miralles, et al. 10Th Congress of Retroviruses and Opportunistic infections. 2003. Characteristics and outcome of AIDS-related non-Hodgkin's lymphoma before and alter the introduction of HAART (GESIDA 23/01). Abstract 802
• Background Simonelli C, Spina M, Cinelli R, Talamini R, Tedeschi R, Gloghini A, Vaccher E, Carbone A, Tirelli U. Clinical features and outcome of primary effusion lymphoma in HIV-infected patients: a single-institution study. J Clin Oncol. 2003 Nov 1;21(21):3948-54. doi: 10.1200/JCO.2003.06.013.
• Background Pantanowitz Lbeckwith B, Dezube BJ. HIV-associated plasma cell neoplasia. HIV AIDS Rev 2004; 3: 47-50.
• Background Mate JL, Navarro JT, Ariza A, Ribera JM, Castella E, Junca J, Tural C, Nomdedeu JF, Bellosillo B, Serrano S, Granada I, Milla F, Feliu E. Oral solid form of primary effusion lymphoma mimicking plasmablastic lymphoma. Hum Pathol. 2004 May;35(5):632-5. doi: 10.1016/j.humpath.2003.11.005.
• Background Navarro JT, Ribera JM, Junca J, Milla F. Anorectal lymphoma without effusion associated with human herpesvirus-8 and type 1 Epstein-Barr virus in an HIV-infected patient. Hum Pathol. 2003 Jun;34(6):630. doi: 10.1016/s0046-8177(03)00093-5. No abstract available.
• Background Skiest DJ, Crosby C. Survival is prolonged by highly active antiretroviral therapy in AIDS patients with primary central nervous system lymphoma. AIDS. 2003 Aug 15;17(12):1787-93. doi: 10.1097/00002030-200308150-00007.
• Background JM Ribera, A Oriol, M Morgades, E Gonzalez-Barca, A López-Guillermo, A López, et al. Treatment with rituximab, CHOP and highly active antiretroviral therapy (HAART) in AIDS-related diffuse large B-cell lymphomas (DLBCL). Study of 60 patients. American Society of Hematology. 47th Annual Meeting. Atlanta, December 10-13, 2005. Abstract 774. Blood 2005, 106 (11): 228a.
• Background Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. doi: 10.1056/NEJMoa011795.
• Background Pfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rube C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. doi: 10.1182/blood-2003-06-2094. Epub 2004 Feb 24.
• Background Pfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rube C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. doi: 10.1182/blood-2003-06-2095. Epub 2004 Mar 11.
• Background Tanosaki R, Okamoto S, Akatsuka N, Ishida A, Michikawa N, Masuda Y, Uchida H, Murata M, Kizaki M, Ikeda Y. Dose escalation of biweekly cyclophosphamide, doxorubicin, vincristine, and prednisolone using recombinant human granulocyte colony stimulating factor in non-Hodgkin's lymphoma. Cancer. 1994 Oct 1;74(7):1939-44. doi: 10.1002/1097-0142(19941001)74:73.0.co;2-c.
• Background Grigg A, Solal-Celigny P, Hoskin P, Taylor K, McMillan A, Forstpointner R, Bacon P, Renwick J, Hiddemann W; International Study Group. Open-label, randomized study of pegfilgrastim vs. daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkin's lymphoma. Leuk Lymphoma. 2003 Sep;44(9):1503-8. doi: 10.1080/1042819031000103953.
• Background Lopez A, Fernandez de Sevilla, A, Castaigne S, Greil R, Sierra J, Sanchez J, et al. Pegfigrastim supports delivery of CHOP-R chemotherapy administered every 14 days: a randomised phase II study. Blood 2004; 104: 904a-905a (abstract 3311).
• Background Spina M, Jaeger U, Sparano JA, Talamini R, Simonelli C, Michieli M, Rossi G, Nigra E, Berretta M, Cattaneo C, Rieger AC, Vaccher E, Tirelli U. Rituximab plus infusional cyclophosphamide, doxorubicin, and etoposide in HIV-associated non-Hodgkin lymphoma: pooled results from 3 phase 2 trials. Blood. 2005 Mar 1;105(5):1891-7. doi: 10.1182/blood-2004-08-3300. Epub 2004 Nov 18.
• Background Boue F, Gabarre J, Gisselbrecht Ch, Reynes J, Plantier I, Morlat P, et al. CHOP chemotherapy plus rituximab in HIV patients with high-grade lymphoma. Results of an ANRS trial. 44th Annual Meeting of the American Society of Hematology 2002. Blood 2002; 100 (suppl): 470a.
• Background Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. doi: 10.1182/blood-2005-04-1437. Epub 2005 May 24.
• Background Oriol A, Ribera JM, Esteve J, Sanz MA, Brunet S, Garcia-Boyero R, Fernandez-Abellan P, Marti JM, Abella E, Sanchez-Delgado M, Penarrubia MJ, Besalduch J, Moreno MJ, Borrego D, Feliu E, Ortega JJ; PETHEMA Group, Spanish Society of Hematology. Lack of influence of human immunodeficiency virus infection status in the response to therapy and survival of adult patients with mature B-cell lymphoma or leukemia. Results of the PETHEMA-LAL3/97 study. Haematologica. 2003 Apr;88(4):445-53.
• Background Oriol A, Ribera JM, Brunet S, del Potro E, Abella E, Esteve J. Highly active antiretroviral therapy and outcome of AIDS-related Burkitt's lymphoma or leukemia. Results of the PETHEMA-LAL3/97 study. Haematologica. 2005 Jul;90(7):990-2.
• Background Thomas DA, Cortes J, Giles FJ, Faderl S, O'Brien S, Garcia-Manero G, et al. Rituximab and hyper-CVAD for adult Burkitt's or Burkitt-like leukemia or lymphoma. 44th Annual Meeting of the American Society of Hematology 2002. Blood 2002; 100 Suppl 763a.
• Background Bokemeyer C, Aapro MS, Courdi A, Foubert J, Link H, Osterborg A, Repetto L, Soubeyran P. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer. Eur J Cancer. 2004 Oct;40(15):2201-16. doi: 10.1016/j.ejca.2004.07.015.
• Background Miralles P, Rubio C, Berenguer J, Ribera JM, Calvo F, Diaz Mediavilla J, Diez-Martin JL, Lopez Aldeguer J, Valencia E, Rubio R. [GESIDA/PETHEMA guidelines for the diagnosis and treatment of lymphomas in HIV-infected patients]. Med Clin (Barc). 2002 Feb 23;118(6):225-36. doi: 10.1016/s0025-7753(02)72342-7. No abstract available. Spanish.
• Background Juweid ME, Wiseman GA, Vose JM, Ritchie JM, Menda Y, Wooldridge JE, Mottaghy FM, Rohren EM, Blumstein NM, Stolpen A, Link BK, Reske SN, Graham MM, Cheson BD. Response assessment of aggressive non-Hodgkin's lymphoma by integrated International Workshop Criteria and fluorine-18-fluorodeoxyglucose positron emission tomography. J Clin Oncol. 2005 Jul 20;23(21):4652-61. doi: 10.1200/JCO.2005.01.891. Epub 2005 Apr 18.

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