R-CHOP-14 Versus R-CHOP-21 and Darbepoetin Alpha in Patients Aged 60-80 Years With Diffuse Large B-cell Lymphoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2011 by Lymphoma Study Association.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Amgen
Information provided by:
Lymphoma Study Association
ClinicalTrials.gov Identifier:
NCT00144755
First received: September 2, 2005
Last updated: March 3, 2011
Last verified: March 2011
  Purpose

This study is a multicentric randomized trial evaluating the efficacy and safety of R-CHOP given every 14 days compared to R-CHOP given every 21 days in association or not with darbepoetin alfa in order to maintain hemoglobin above 13 g/dl, compared to classical symptomatic treatment of anemia in patients aged from 60 to 80 years with diffuse large B-cell lymphoma.


Condition Intervention Phase
Diffuse Large Cell Lymphoma
Drug: R-CHOP21
Drug: R-CHOP14
Drug: Darbepoetin alfa
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intensified CHOP Plus Rituximab (R-CHOP 14) Versus CHOP Plus Rituximab (R-CHOP 21) and Frontline/Prophylactic Darbepoetin Alfa Treatment Versus Usual Symptomatic Treatment of Anemia in Patients Aged 60 to 80 Years With Diffuse Large B-cell Lymphoma.

Resource links provided by NLM:


Further study details as provided by Lymphoma Study Association:

Primary Outcome Measures:
  • Efficacy of R-CHOP 14 vs R-CHOP 21 measured by event-free survival (EFS) [ Time Frame: event-free survival ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy of darbepoetin alfa in association with chemotherapy measured by the EFS. [ Time Frame: event-free survival ] [ Designated as safety issue: No ]
  • Efficacy and toxicity of R-CHOP 14 vs R-CHOP 21 [ Time Frame: CR rate, DFS, OS, dose intensity and additional toxicities. ] [ Designated as safety issue: Yes ]
  • Efficacy and toxicity of Darbepoetin alfa in association with R-CHOP. [ Designated as safety issue: Yes ]

Enrollment: 600
Study Start Date: December 2003
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: R-CHOP21 Drug: R-CHOP21
Experimental: R-CHOP21, Darbepoetin alfa Drug: R-CHOP21 Drug: Darbepoetin alfa
Experimental: R-CHOP14 Drug: R-CHOP14
Experimental: R-CHOP14, Darbepoetin alfa Drug: R-CHOP14 Drug: Darbepoetin alfa

Detailed Description:

In patients aged 60 to 75 years with diffuse large B-cell lymphoma, the shortening of interval between the courses of CHOP combination (CHOP-14), improves the complete response rate, the progression free survival and the overall survival.

The addition of Rituximab to standard CHOP (R-CHOP) has also been shown to improve complete remission rate (CR), event-free survival (EFS) and overall survival (OS) in elderly patients with B-DLCL.

The aim of this study is to test the hypothesis that the increase of the dose intensity by shortening the interval between two courses of R-CHOP (R-CHOP-14)could further improve the results of the R-CHOP.

Anemia is frequent at diagnosis and during the treatment of aggressive lymphoma. In the previous LNH 98-5 study, 72 % of the patients had, at the diagnosis, a hemoglobin level inferior to 13 g/dl. Moreover, during the treatment, 92 % of the patients had a hemoglobin level less than 13 g/dl and 30 % were transfused. The presence of anemia at diagnosis is an indicator of poor prognosis in multivariate analysis. This prognosis impact could probably be explained at cellular level on the tumor. Tumoral hypoxia is increased by the presence of anemia. Due to this hypoxia, the expression of tumor growth factor may be increased: e.a VEGF and the induction of expression of multi drug resistance (MDR1) is observed. This resistance to treatment is also due to the inhibition of genotoxic activity of free radicals induced by ionised radiation and chemotherapy. Experimentally, the negative impact of hypoxia on the efficacy of chemotherapy has been demonstrated in sarcoma cell lines for doxorubicin, vincristine and all most cyclophosphamide. Finally, hypoxia induced over expression of apoptosis resistance genes and induced a growth advantage for apoptosis resistant tumoral lines. Improvement of survival in patients receiving erythropoetin with chemotherapy or radiotherapy was suggested in a study on patients treated with a neoadjuvant radiochemotherapy for head and neck cancer. Erythropoetin could act to protect several normal tissues during chemotherapy and thus could decrease treatment related morbidity. Darbepoetin alfa is a new recombinant protein stimulating erythropoiesis. Thus, the use of darbepoetin alfa, in association with chemotherapy, could increase CR rate, EFS and OS in patients treated for diffuse large B-cell lymphoma.

This study is a multicentric, phase III open-label, randomized trial evaluating the efficacy and safety of R-CHOP given every 14 days compared to R-CHOP given every 21 days in association or not with darbepoetin alfa in order to maintain hemoglobin above 13 g/dl, compared to classical symptomatic treatment of anemia in patients aged 66 to 80 years with not previously treated diffuse large B-cell lymphoma with at least one adverse prognostic factor of the age adjusted IPI.

  Eligibility

Ages Eligible for Study:   60 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients with histologically proven CD20+ diffuse large B cell lymphoma (WHO Classification).

Aged 66 to 80 years old. Patients not previously treated. Ann Arbor stage II, III, IV. ECOG performance status 0 to 2. Age-adjusted IPI equal to 1, 2, or 3. With a minimum life expectancy of 3 months. Negative HIV, HBV and HCV serologies test < 4 weeks (except after vaccination for HBV).

Having signed a written informed consent.

Exclusion Criteria:

Any other histological type of lymphoma. Any history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed and having a diffuse large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included.

Central nervous system or meningeal involvement by lymphoma. Contra-indication to any drug contained in the chemotherapy regimens. Any serious co-morbid active disease (according to the investigator's decision).

Poor renal function (creatinin level > 150 micromol/l), poor hepatic function (total bilirubin level > 30mmol/l, transaminases > 2.5 maximum normal level) unless these abnormalities are related to the lymphoma.

Poor bone marrow reserve as defined by neutrophils < 1.5 G/l or platelets < 100 G/l, unless related to bone marrow infiltration.

Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma.

Uncontrolled hypertension. Known hypersensitivity to erythropoietin. Myocardial infarction during last 3 month, or unstable coronary disease, or uncontrolled cardiac insufficiency.

Venous thrombosis or pulmonary embolism during last 3 months. Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study.

Pregnant or lactating women. Adult patient under tutelage.

  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: NCT00144755

Locations
Belgium
Université de Gent
Gent, Belgium
Groupe d'Etude des Lymphomes de l'adulte
Mont-Godinne, Belgium
France
Polyclinique Bordeaux Nord
Bordeaux, France, 33300
Hôpital Henri Mondor
Créteil, France, 94010
Hématologie CHU de Lille
Lille, France, 59000
Centre Léon Bérard
Lyon, France, 69008
Hématologie Adultes - Hôpital Necker
Paris, France, 75743
Hôpital Saint Louis
Paris, France, 75010
Service d'Hématologie - Centre Hospitalier Lyon-Sud
Pierre-Bénite cedex, France, 69495
Centre Hospitalier Robert Debré
Reims, France, 51092
Centre Henri Becquerel
Rouen, France, 76038
Hématologie CHU Purpan
Toulouse, France, 31059
Institut Gustave Roussy
Villejuif, France
Switzerland
Schweirische Arbeitsgruppe fur klinische Krebsforschung
Lausanne, Switzerland
Sponsors and Collaborators
Lymphoma Study Association
Amgen
Investigators
Principal Investigator: Richard Delarue, MD Lymphoma Study Association
Study Director: André Bosly, MD Lymphoma Study Association
Study Chair: Corinne Haioun, MD Lymphoma Study Association
Study Chair: Hervé Tilly, MD Lymphoma Study Association
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Richard DELARUE, MD, Groupe d'Etude des Lymphomes de l'Adulte
ClinicalTrials.gov Identifier: NCT00144755     History of Changes
Other Study ID Numbers: LNH03-6B
Study First Received: September 2, 2005
Last Updated: March 3, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Lymphoma Study Association:
lymphoma, diffuse large B-cell
rituximab
chemotherapy
erythropoetin
darbepoetin alfa

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Darbepoetin alfa
Hematinics
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014