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

September 1, 2015 updated by: Lymphoma Study Association

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

600

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Gent, Belgium
        • Université de Gent
      • Mont-Godinne, Belgium
        • Groupe d'Etude des Lymphomes de l'Adulte
  • France
      • Bordeaux, France, 33300
        • Polyclinique Bordeaux Nord
      • Créteil, France, 94010
        • Hopital Henri Mondor
      • Lille, France, 59000
        • Hématologie CHU de Lille
      • Lyon, France, 69008
        • Centre Leon Bérard
      • Paris, France, 75010
        • Hopital Saint Louis
      • Paris, France, 75743
        • Hématologie Adultes - Hôpital Necker
      • Pierre-Bénite cedex, France, 69495
        • Service d'Hématologie - Centre Hospitalier Lyon-Sud
      • Reims, France, 51092
        • Centre Hospitalier Robert Debre
      • Rouen, France, 76038
        • Centre Henri Becquerel
      • Toulouse, France, 31059
        • Hématologie CHU Purpan
      • Villejuif, France
        • Institut Gustave Roussy
  • Switzerland
      • Lausanne, Switzerland
        • Schweirische Arbeitsgruppe fur klinische Krebsforschung

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: R-CHOP21
8 cycles of R-CHOP21
Drug: Darbepoetin alfa
prophylactic administration of darbepoetin alfa in experimental arm
Experimental: R-CHOP21, Darbepoetin alfa
8 cycles of R-CHOP21 + prophylactic darbepoetin alfa
Drug: Darbepoetin alfa
prophylactic administration of darbepoetin alfa in experimental arm
Experimental: R-CHOP14
8 cycles of R-CHOP14
Drug: Darbepoetin alfa
prophylactic administration of darbepoetin alfa in experimental arm
Experimental: R-CHOP14, Darbepoetin alfa
8 cycles of R-CHOP14 + prophylactic darbepoetin alfa
Drug: Darbepoetin alfa
prophylactic administration of darbepoetin alfa in experimental arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy of R-CHOP 14 vs R-CHOP 21 measured by event-free survival (EFS)
Time Frame: 8 years
8 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of darbepoetin alfa in association with chemotherapy measured by the EFS.
Time Frame: 8 years
8 years
Efficacy and toxicity of R-CHOP 14 vs R-CHOP 21
Time Frame: 8 years
CR rate, DFS, OS, dose intensity and additional toxicities.
8 years
Efficacy and toxicity of Darbepoetin alfa in association with R-CHOP.
Time Frame: 8 years
event-free survival
8 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lymphoma Study Association

Collaborators

Amgen

Investigators

  • Principal Investigator: Richard Delarue, MD, Lymphoma Study Association
  • Study Chair: Hervé Tilly, MD, Lymphoma Study Association
  • Study Chair: Corinne Haioun, MD, Lymphoma Study Association
  • Study Director: André Bosly, MD, Lymphoma Study Association

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2003

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

September 2, 2005

First Submitted That Met QC Criteria

September 2, 2005

First Posted (Estimate)

September 5, 2005

Study Record Updates

Last Update Posted (Estimate)

September 2, 2015

Last Update Submitted That Met QC Criteria

September 1, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LNH03-6B

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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