R-CHOP-14 Versus R-CHOP-21 and Darbepoetin Alpha in Patients Aged 60-80 Years With Diffuse Large B-cell Lymphoma
Recruitment status was Active, not recruiting
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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. |
- 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 ]
- 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 |
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| 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 | |
| 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:
| 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, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Rituximab Darbepoetin alfa Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents Hematinics Hematologic Agents |
ClinicalTrials.gov processed this record on May 21, 2013