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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) (LINFOTARGAM)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00466258
First Posted: April 27, 2007
Last Update Posted: November 25, 2009
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
PETHEMA Foundation
  Purpose

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).

Condition Intervention Phase
HIV Infections Diffuse Large B Cell Lymphoma Drug: R-CHOP Drug: Highly active antiretroviral therapy Drug: Central nervous system (CNS) prophylaxis Drug: Prophylaxis of opportunistic infections and support treatment Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: LINFOTARGAM: First-line Treatment With Dose-dense Chemotherapy Plus Rituximab (R-CHOP/14) and Highly Active Antiretroviral Therapy (HAART) in Patients With Diffuse Large B Cell Lymphoma (DLBCL) and Infection With the Human Immunodeficiency Virus (HIV)

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • treatment toxicity according to the CTC criteria (version 3.0) of the National Cancer Institute (NCI) [ Time Frame: 6 months ]
  • opportunistic and non-opportunistic infections rate after 6 cycles of treatment with R-CHOP administered every 14 days and HAART in patients with DLBCL and HIV infection [ Time Frame: 6 months ]
  • 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) [ Time Frame: 6 months ]

Secondary Outcome Measures:
  • efficacy of the treatment in patients with DLBCL and HIV infection after 6 cycles of treatment with R-CHOP administered every 14 days [ Time Frame: 1 year ]
  • global response and complete remission rate [ Time Frame: 1 year ]
  • duration of the response [ Time Frame: 5 years ]
  • event-free survival probability in 5 years [ Time Frame: 5 years ]
  • global survival probability in 5 years [ Time Frame: 5 years ]
  • predictive factors of the response after 6 cycles of treatment with R-CHOP administered every 14 days in patients with DLBCL and HIV infection [ Time Frame: 2 years ]
  • impact of the therapeutic combination of R-CHOP and HAART in the parameters of the HIV infection (HIV viral load and CD4+ lymphocyte count) [ Time Frame: 1 year ]

Estimated Enrollment: 50
Study Start Date: October 2006
Study Completion Date: November 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: R-CHOP
    • Cyclophosphamide 750 mg/m2 i.v. day 1
    • Adriamycin 50 mg/m2 i.v. day 1
    • Vincristine 1,4 mg/m2 i.v. day 1
    • Prednisone 100 mg i.v or oral. days 1-5.
    Drug: Highly active antiretroviral therapy
    Combined antiretroviral treatment (TARGA) wich include at lest 3 drugs. The combination should be accepted as an initial or rescue treatment.
    Drug: Central nervous system (CNS) prophylaxis
    methotrexate (12 mg) cytarabine (30 mg) hydrocortisone (20 mg)
    Drug: Prophylaxis of opportunistic infections and support treatment
    Pegfilgrastim
Detailed Description:
This is a clinical trial with a pharmaceutical drug used in the same conditions of authorization.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with HIV infection diagnosed with DLBCL in any stage (I-IV according to the Ann Arbor classification) not previously treated for the lymphoma.
  • Patients with CD20-positive diffuse large B-cell lymphoma
  • Aged from 18 to 70 years old
  • Any score of International Prognostic Index. (It is also applicable in patients with non-Hodgkin lymphoma [NHL] infected with HIV.)
  • ECOG performance status 0 to 3
  • Written informed consent
  • Absolute neutrophil count > 1.5 x 10^9/L.
  • Absence of synchronic or non-synchronic neoplasia with the exception of non-melanoma skin tumors or in situ cervical carcinoma.
  • CD4+ lymphocyte count > 100/µL

Exclusion Criteria:

  • Patients with diffuse large B cell lymphoma previously treated.
  • Patients with primary central nervous system lymphoma.
  • Patients with Burkitt or Burkitt-like NHL.
  • CD4+ lymphocyte count < 100/µL
  • Opportunistic infections or other AIDS-related neoplasias in activity.
  • Active drug-addiction.
  • Pregnant or lactating women or adults of fertile age who do not use an effective contraceptive method.
  • Patients with serious altered renal function (creatinine > 2.5 x upper limit of normal [ULN]) or hepatic [bilirubin, ALT or AST > 2.5 x ULN], except if the investigators suspect that they are caused by the disease.
  • Cardiac insufficiency with ejection fraction < 40%
  • Patients with serious psychiatric diseases that can interfere with their capacity to understand the study (including alcoholism or active drug-addiction).
  • ECOG > 3
  • Patients with a known hypersensitivity to murine proteins or any other component of the study drugs.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00466258


Locations
Spain
H. Son Llatzer
Palma de Mallorca, Baleares, Spain
Germans Trias i Pujol
Badalona, Barcelona, Spain
Consorci Sanitari de Mataró
Mataro, Barcelona, Spain
H. Parc Taulí
Sabadell, Barcelona, Spain
Consorci Sanitari de Terrassa
Terrassa, Barcelona, Spain
Hospital de Navarra
Pamplona, Navarra, Spain
H. Clínic i Provincial, Barcelona
Barcelona, Spain
H. Vall d'Hebron, Barcelona
Barcelona, Spain
Hospital del Mar
Barcelona, Spain
Hospital Sant Pau, Barcelona
Barcelona, Spain
ICO - Duran i Reynals, Hospitalet de Llobregat
Barcelona, Spain
ICO - Josep Trueta
Girona, Spain
H. Gregorio Marañón
Madrid, Spain
H. Joan XXIII
Tarragona, Spain
Hospital Universitario Dr. Peset
Valencia, Spain
Sponsors and Collaborators
PETHEMA Foundation
Investigators
Principal Investigator: Ribera Josep M, Dr Germans Trias i Pujol Hospital
Principal Investigator: Oriol Albert, Dr Germans Trias i Pujol Hospital
  More Information

Additional Information:
Publications:
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.
Noy A. Update in HIV-associated lymphoma. Curr Opin Oncol. 2004 Sep;16(5):450-4. Review.
Bonnet F, Lewden C, May T, Heripret L, Jougla E, Bevilacqua S, Costagliola D, Salmon D, Chêne 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.
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.
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. Spanish.
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.
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.
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. Epub 2003 Dec 5.
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
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.
Pantanowitz Lbeckwith B, Dezube BJ. HIV-associated plasma cell neoplasia. HIV AIDS Rev 2004; 3: 47-50.
Mate JL, Navarro JT, Ariza A, Ribera JM, Castellà E, Juncà J, Tural C, Nomdedeu JF, Bellosillo B, Serrano S, Granada I, Millá F, Feliu E. Oral solid form of primary effusion lymphoma mimicking plasmablastic lymphoma. Hum Pathol. 2004 May;35(5):632-5.
Navarro JT, Ribera JM, Juncà J, Millá 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.
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.
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.
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.
Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe 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. Epub 2004 Feb 24.
Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe 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. Epub 2004 Mar 11.
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.
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.
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).
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. Epub 2004 Nov 18.
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.
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. Epub 2005 May 24.
Oriol A, Ribera JM, Esteve J, Sanz MA, Brunet S, Garcia-Boyero R, Fernández-Abellán P, Martí JM, Abella E, Sánchez-Delgado M, Peñarrubia 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.
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.
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.
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. Review.
Miralles P, Rubio C, Berenguer J, Ribera JM, Calvo F, Diaz Mediavilla J, Diez-Martín JL, López 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. Review. Spanish. Erratum in: Med Clin (Barc). 2002 Apr 27;118(15):582. Felipe C [corrected to Calvo F].
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. Epub 2005 Apr 18.

Responsible Party: Pethema, pethema
ClinicalTrials.gov Identifier: NCT00466258     History of Changes
Other Study ID Numbers: 2006-003750-23
LINFOTARGAM
First Submitted: April 25, 2007
First Posted: April 27, 2007
Last Update Posted: November 25, 2009
Last Verified: November 2009

Keywords provided by PETHEMA Foundation:
Diffuse large B cell lymphoma
HIV
R-CHOP
Highly active antiretroviral therapy
Treatment Experienced

Additional relevant MeSH terms:
Lymphoma
Infection
Communicable Diseases
HIV Infections
Lymphoma, B-Cell
Immunologic Deficiency Syndromes
Lymphoma, Large B-Cell, Diffuse
Acquired Immunodeficiency Syndrome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lymphoma, Non-Hodgkin
Slow Virus Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents


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