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)

This study has been completed.
Sponsor:
Information provided by:
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT00466258
First received: April 25, 2007
Last updated: November 23, 2009
Last verified: November 2009
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • global response and complete remission rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • duration of the response [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • event-free survival probability in 5 years [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • global survival probability in 5 years [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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. Vall d'Hebron, Barcelona
Barcelona, Spain
H. Clínic i Provincial, Barcelona
Barcelona, Spain
Hospital Sant Pau, Barcelona
Barcelona, Spain
ICO - Duran i Reynals, Hospitalet de Llobregat
Barcelona, Spain
Hospital del Mar
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:
JM Ribera, JT Navarro. Linfomas en pacientes con infección por el VIH. Las cosas han cambiado para bien. Enf Infecc Microbiol Clin 2004; 22: 313-314.
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
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.
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).
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.
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.

Responsible Party: Pethema, pethema
ClinicalTrials.gov Identifier: NCT00466258     History of Changes
Other Study ID Numbers: 2006-003750-23, LINFOTARGAM
Study First Received: April 25, 2007
Last Updated: November 23, 2009
Health Authority: Spain: Ministry of Health

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

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

ClinicalTrials.gov processed this record on October 19, 2014