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Diffuse Large Cell LymphomaPhase 3NCT00144755

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

A Phase 3 study testing Darbepoetin alfa in people with Diffuse Large Cell Lymphoma, run by Lymphoma Study Association at 14 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 60 to 80 years
Conditions the study is for
Diffuse Large Cell Lymphoma
What is being tested?
Darbepoetin alfa
Could I receive a placebo?
No, everyone receives an active treatment
How many people
600 participants
Where
14 sitesin 3 countries
Study dates
Dec 2003to Dec 2012
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

14 sites in 3 countries.

14 sites in 3 countries

France11 sites

  • Polyclinique Bordeaux Nord

    Bordeaux, 33300

  • Hôpital Henri Mondor

    Créteil, 94010

  • Hématologie CHU de Lille

    Lille, 59000

  • Centre Léon Bérard

    Lyon, 69008

  • Hôpital Saint Louis

    Paris, 75010

  • Hématologie Adultes - Hôpital Necker

    Paris, 75743

  • Service d'Hématologie - Centre Hospitalier Lyon-Sud

    Pierre-Bénite, 69495

  • Centre Hospitalier Robert Debré

    Reims, 51092

  • Centre Henri Becquerel

    Rouen, 76038

  • Hématologie CHU Purpan

    Toulouse, 31059

  • Institut Gustave Roussy

    Villejuif

Other trials in France

Belgium2 sites

  • Université de Gent

    Ghent

  • Groupe d'Etude des Lymphomes de l'adulte

    Mont-Godinne

Other trials in Belgium

Switzerland1 site

  • Schweirische Arbeitsgruppe fur klinische Krebsforschung

    Lausanne

Other trials in Switzerland

About this study

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.

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.

Read the 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.

Being tested
Darbepoetin alfa
Keywords
lymphoma, diffuse large B-cell, rituximab, chemotherapy, erythropoetin, darbepoetin alfa
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Darbepoetin alfaDrug

    prophylactic administration of darbepoetin alfa in experimental arm

Study groups in NCT00144755
Study groupRoleWhat they receive
R-CHOP21Active comparator8 cycles of R-CHOP21
Receives: Drug: Darbepoetin alfa
R-CHOP21, Darbepoetin alfaExperimental8 cycles of R-CHOP21 + prophylactic darbepoetin alfa
Receives: Drug: Darbepoetin alfa
R-CHOP14Experimental8 cycles of R-CHOP14
Receives: Drug: Darbepoetin alfa
R-CHOP14, Darbepoetin alfaExperimental8 cycles of R-CHOP14 + prophylactic darbepoetin alfa
Receives: Drug: Darbepoetin alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy of R-CHOP 14 vs R-CHOP 21 measured by event-free survival (EFS)

    Measured: 8 years

Secondary outcomes (3)

  1. Efficacy of darbepoetin alfa in association with chemotherapy measured by the EFS.

    Measured: 8 years

  2. Efficacy and toxicity of R-CHOP 14 vs R-CHOP 21

    CR rate, DFS, OS, dose intensity and additional toxicities.

    Measured: 8 years

  3. Efficacy and toxicity of Darbepoetin alfa in association with R-CHOP.

    event-free survival

    Measured: 8 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2005 (estimated)
  2. Study startDec 2003
  3. Primary completionDec 2012
  4. Study completionDec 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
600 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00144755
Sponsor's protocol ID
LNH03-6B
Status last verified
Sep 2015
First submitted
2 Sep 2005
Last updated
2 Sep 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. doi: 10.1200/JCO.2005.09.131. Epub 2005 May 2.

    PubMed 15867204

  • Pfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rube C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. doi: 10.1182/blood-2003-06-2095. Epub 2004 Mar 11.

    PubMed 15016643

  • Camus V, Belot A, Oberic L, Sibon D, Ghesquieres H, Thieblemont C, Fruchart C, Casasnovas O, Michot JM, Molina TJ, Bosly A, Joubert C, Haioun C, Nicolas-Virelizier E, Feugier P, Fitoussi O, Delarue R, Tilly H. Outcomes of older patients with diffuse large B-cell lymphoma treated with R-CHOP: 10-year follow-up of the LNH03-6B trial. Blood Adv. 2022 Dec 27;6(24):6169-6179. doi: 10.1182/bloodadvances.2022007609.

    PubMed 35737565

  • Petrella T, Copie-Bergman C, Briere J, Delarue R, Jardin F, Ruminy P, Thieblemont C, Figeac M, Canioni D, Feugier P, Fabiani B, Leroy K, Parrens M, Andre M, Haioun C, Salles GA, Gaulard P, Tilly H, Jais JP, Molina TJ. BCL2 expression but not MYC and BCL2 coexpression predicts survival in elderly patients with diffuse large B-cell lymphoma independently of cell of origin in the phase 3 LNH03-6B trial. Ann Oncol. 2017 May 1;28(5):1042-1049. doi: 10.1093/annonc/mdx022.

    PubMed 28327893

  • Ghesquieres H, Larrabee BR, Haioun C, Link BK, Verney A, Slager SL, Ketterer N, Ansell SM, Delarue R, Maurer MJ, Fitoussi O, Habermann TM, Peyrade F, Dogan A, Molina TJ, Novak AJ, Tilly H, Cerhan JR, Salles G. FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts. Hematol Oncol. 2017 Dec;35(4):447-455. doi: 10.1002/hon.2305. Epub 2016 Jun 10.

    PubMed 27282998

  • Copie-Bergman C, Cuilliere-Dartigues P, Baia M, Briere J, Delarue R, Canioni D, Salles G, Parrens M, Belhadj K, Fabiani B, Recher C, Petrella T, Ketterer N, Peyrade F, Haioun C, Nagel I, Siebert R, Jardin F, Leroy K, Jais JP, Tilly H, Molina TJ, Gaulard P. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study. Blood. 2015 Nov 26;126(22):2466-74. doi: 10.1182/blood-2015-05-647602. Epub 2015 Sep 15.

    PubMed 26373676

  • Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquieres H, Hacini M, Fruchart C, Ysebaert L, Ferme C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. doi: 10.1016/S1470-2045(13)70122-0. Epub 2013 Apr 9.

    PubMed 23578722

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Darbepoetin alfa in people with Diffuse Large Cell Lymphoma, run by Lymphoma Study Association at 14 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in France, Belgium, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of R-CHOP 14 vs R-CHOP 21 measured by event-free survival (EFS) (time frame: 8 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00144755, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2015.

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