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

NCT00144755 | Completed Phase 3 DMC

• 1 other identifier: LNH03-6B
• Study Type: interventional
• Target: 600
• Locations: 3 countries
• Sites: 14

Brief 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 to 80 years with diffuse large B-cell lymphoma.

Conditions

Diffuse Large Cell Lymphoma

Keywords

lymphoma, diffuse large B-cell; rituximab; chemotherapy; erythropoetin; darbepoetin alfa

Outcome Measures

Primary Outcomes (1)

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

  8 years

Secondary Outcomes (3)

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

  8 years

• Efficacy and toxicity of R-CHOP 14 vs R-CHOP 21

  8 years

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

  8 years

Study Arms (4)

R-CHOP21

ACTIVE COMPARATOR

8 cycles of R-CHOP21

Drug: Darbepoetin alfa

R-CHOP21, Darbepoetin alfa

EXPERIMENTAL

8 cycles of R-CHOP21 + prophylactic darbepoetin alfa

Drug: Darbepoetin alfa

R-CHOP14

EXPERIMENTAL

8 cycles of R-CHOP14

Drug: Darbepoetin alfa

R-CHOP14, Darbepoetin alfa

EXPERIMENTAL

8 cycles of R-CHOP14 + prophylactic darbepoetin alfa

Drug: Darbepoetin alfa

Interventions

Darbepoetin alfa DRUG

prophylactic administration of darbepoetin alfa in experimental arm

R-CHOP14; R-CHOP14, Darbepoetin alfa; R-CHOP21; R-CHOP21, Darbepoetin alfa

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lymphoma Study Association: lead
• Amgen: collaborator

Study Sites (14)

Université de Gent

Ghent, Belgium

Location

Groupe d'Etude des Lymphomes de l'adulte

Mont-Godinne, Belgium

Location

Polyclinique Bordeaux Nord

Bordeaux, 33300, France

Location

Hôpital Henri Mondor

Créteil, 94010, France

Location

Hématologie CHU de Lille

Lille, 59000, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Hématologie Adultes - Hôpital Necker

Paris, 75743, France

Location

Service d'Hématologie - Centre Hospitalier Lyon-Sud

Pierre-Bénite, 69495, France

Location

Centre Hospitalier Robert Debré

Reims, 51092, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Hématologie CHU Purpan

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Schweirische Arbeitsgruppe fur klinische Krebsforschung

Lausanne, Switzerland

Location

Related Publications (7)

• 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.

  PMID: 15867204 BACKGROUND

• 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.

  PMID: 15016643 BACKGROUND

• 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.

  PMID: 35737565 DERIVED

• 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.

  PMID: 28327893 DERIVED

• 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.

  PMID: 27282998 DERIVED

• 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.

  PMID: 26373676 DERIVED

• 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.

  PMID: 23578722 DERIVED

Related Links

• Official site of the Groupe d'Etudes des Lymphomes de l'Adulte (In french)

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Darbepoetin alfa

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Richard Delarue, MD

  Lymphoma Study Association

  PRINCIPAL INVESTIGATOR

• André Bosly, MD

  Lymphoma Study Association

  STUDY DIRECTOR

• Corinne Haioun, MD

  Lymphoma Study Association

  STUDY CHAIR

• Hervé Tilly, MD

  Lymphoma Study Association

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2005
• First Posted: September 5, 2005
• Study Start: December 1, 2003
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: September 2, 2015

Record last verified: 2015-09

Locations

BE (2); CH (1); FR (11)