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)

HIV Infections Clinical Trial

— LINFOTARGAM  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00466258
• Other study ID #: 2006-003750-23
• Secondary ID: LINFOTARGAM
• Status: Completed
• Phase: Phase 4
• First received: April 25, 2007
• Last updated: November 23, 2009
• Start date: October 2006
• Est. completion date: November 2009

Study information

• Verified date: November 2009
• Source: PETHEMA Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial 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).

Description:

This is a clinical trial with a pharmaceutical drug used in the same conditions of authorization.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: November 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Diffuse Large B Cell Lymphoma
• HIV Infections
• Immunologic Deficiency Syndromes
• Infection
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

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.
• 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.
• Central nervous system (CNS) prophylaxis
methotrexate (12 mg) cytarabine (30 mg) hydrocortisone (20 mg)
• Prophylaxis of opportunistic infections and support treatment
Pegfilgrastim

Locations

Country	Name	City	State
Spain	Germans Trias i Pujol	Badalona	Barcelona
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	Consorci Sanitari de Mataró	Mataro	Barcelona
Spain	H. Son Llatzer	Palma de Mallorca	Baleares
Spain	Hospital de Navarra	Pamplona	Navarra
Spain	H. Parc Taulí	Sabadell	Barcelona
Spain	H. Joan XXIII	Tarragona
Spain	Consorci Sanitari de Terrassa	Terrassa	Barcelona
Spain	Hospital Universitario Dr. Peset	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
PETHEMA Foundation

Country where clinical trial is conducted

Spain, 

References & Publications (30)

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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.

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. — View Citation

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. — View Citation

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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. — View Citation

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]. — View Citation

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. — View Citation

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. — View Citation

Noy A. Update in HIV-associated lymphoma. Curr Opin Oncol. 2004 Sep;16(5):450-4. Review. — View Citation

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. — View Citation

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. — View Citation

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	treatment toxicity according to the CTC criteria (version 3.0) of the National Cancer Institute (NCI)		6 months	Yes
Primary	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		6 months	Yes
Primary	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)		6 months	No
Secondary	efficacy of the treatment in patients with DLBCL and HIV infection after 6 cycles of treatment with R-CHOP administered every 14 days		1 year	No
Secondary	global response and complete remission rate		1 year	No
Secondary	duration of the response		5 years	No
Secondary	event-free survival probability in 5 years		5 years	No
Secondary	global survival probability in 5 years		5 years	No
Secondary	predictive factors of the response after 6 cycles of treatment with R-CHOP administered every 14 days in patients with DLBCL and HIV infection		2 years	No
Secondary	impact of the therapeutic combination of R-CHOP and HAART in the parameters of the HIV infection (HIV viral load and CD4+ lymphocyte count)		1 year	No

External Links

•   Pethema Foundation website
•   Spanish Association of Haematology