Efficacy of Lenalidomide in Combination With Subcutaneous Rituximab + miniCHOP in DLBCL Patients of 80 y/o or+

NCT02128061 | Completed Phase 3 DMC

• 1 other identifier: SENIOR
• Study Type: interventional
• Target: 250
• Locations: 2 countries
• Sites: 97

Brief Summary

The purpose of this study is to compare the efficacy of R2-miniCHOP (Sub-cutaneous Rituximab-miniCHOP + lenalidomide) and R-miniCHOP (Sub-cutaneous Rituximab-miniCHOP) in patients aged 80 years old or more with not previously treated cluster of differentiation antigen 20 positive (CD20+) diffuse large B-cell lymphoma as measured by the overall survival (OS).The SENIOR trial will evaluate the tolerance and efficacy of the combination of the R2-miniCHOP regimen and compare this experimental arm to the standard R-miniCHOP regimen.The statistical plan is based on the hypothesis of an increase by 15% of the 2y-OS in favor of the experimental arm, as compared to the reference arm (R-miniCHOP).

Conditions

Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• The overall survival (OS)

  OS will be measured from the date of randomization to the date of death from any cause. Alive patients will be censored at their last contact.

  OS rates at 2 years

Secondary Outcomes (8)

• Progression-Free Survival (PFS)

  PFS rates at 2 years

• Event-Free Survival (EFS)

  EFS rates at 2 years

• Duration of Response (DoR)

  DoR rates at 2 years

• Disease-Free Survival (DFS)

  DFS rates at 2 years

• OS according to GCB/non-GCB phenotype

  OS according to GCB/non-GCB phenotype rates at 2 years

Study Arms (2)

R-miniCHOP

ACTIVE COMPARATOR

All patients will be treated with R-miniCHOP at a three-weeks interval for 6 cycles CYCLOPHOSPHAMIDE IV: 400 mg/m² Day 1 (D1) DOXORUBICINE IV : 25 mg/m² D1 VINCRISTINE IV : 1 mg Total Dose (TD) D1 PREDNISONE PO : 40 mg/m² D1 to D5 RITUXIMAB SC\* : 1400 mg TD D1 \*The first cycle of rituximab is delivered by IV at the dose of 375 mg/m2

Drug: Rituximab

R2-miniCHOP

EXPERIMENTAL

All patients will be treated with R2-miniCHOP at a three-weeks interval for 6 cycles CYCLOPHOSPHAMIDE IV: 400 mg/m² D1 - DOXORUBICINE IV : 25 mg/m² D1 - VINCRISTINE IV : 1 mg TD D1 - PREDNISONE PO : 40 mg/m² D1 to D5 - RITUXIMAB SC\* : 1400 mg TD D1 LENALIDOMIDE PO\*\* :10 mg TD D1 to D14 \*The first cycle of rituximab is delivered by IV at the dose of 375 mg/m2

Drug: Lenalidomide; Drug: Rituximab

Interventions

Lenalidomide DRUG

Also known as: Revlimid

R2-miniCHOP

Rituximab DRUG

Also known as: Mabthera

R-miniCHOP; R2-miniCHOP

Eligibility Criteria

• Age: 80 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Patient with histologically proven CD20+ diffuse large B-cell lymphoma (DLBCL) (WHO classification 2008) including all clinical subtypes (primary mediastinal, intravascular, etc…), with all age-adjusted International Prognostic Index (aaIPI).
• May also be included: De Novo transformed DLBCL from low grade lymphoma (Follicular, other...) and DLBCL associated with some small cell Infiltration in bone marrow or lymph node; or CD20+ B-cell lymphoma, with intermediate features between DLBCL and Burkitt or with intermediate features between DLBCL and classical Hodgkin lymphoma; or CD20+ Follicular lymphoma grade 3B (according to WHO classification); or CD20+ Aggressive B-cell lymphoma unclassifiable.
• With a Cluster of Differentiation antigen 10 (CD10) immunostaining performed by the participating center pathologist
• Aged ≥ 80 years old
• Ann Arbor stage II, III or IV
• Patient previously untreated for DLBCL Lymphoma
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• With a minimum life expectancy of 3 months
• Patient able to give his consent and having signed a written Informed consent
• Patient affiliated to social security system, if applicable
• Male patients must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for 3 months following study drug discontinuation, even if they have undergone a successful vasectomy.
• All patients must agree to fulfill the global Lenalidomide Pregnancy Prevention Risk Management Plan as applicable according to the randomization arm (randomization arm)

You may not qualify if:

• Any other histological type of lymphoma, Burkitt included
• Any history of treated or non-treated small-B cell lymphoma
• Central nervous system or meningeal involvement by lymphoma
• Contra-indication to any drug contained in the chemotherapy regimens ; for anthracycline use, ejection fraction should be \> 50%
• Any serious active disease (according to the investigator's decision)
• Poor renal function (creatinine clearance \< 40 ml/min, according to Modification of Diet in Renal Disease (MDRD) formula)
• 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 Patients previously diagnosed with prostate cancer are eligible if (1) their disease was T1-T2a, N0, M0, with a Gleason score ≤7, and a prostate specific antigen (PSA) ≤10 ng/mL prior to initial therapy, (2) they had definitive curative therapy (i.e., prostatectomy or radiotherapy) 2 years before Day 1 of Cycle 1, and (3) at a minimum 2 years following therapy they had no clinical evidence of prostate cancer, and their PSA was undetectable if they underwent prostatectomy or \<1 ng/mL if they did not undergo prostatectomy
• Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study
• Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy
• Prior use of lenalidomide
• Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide
• Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide
• Subjects with ≥ Grade 2 neuropathy

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• Centre Henri Becquerel: collaborator

Study Sites (97)

ZNA Stuivenberg

Antwerp, Belgium

Location

A. Z. Sint-Jan

Bruges, 8000, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Université Catholique de Louvain Saint Luc

Brussels, 1200, Belgium

Location

Hôpital Erasme

Brussels, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, 6000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

CHR Citadelle

Liège, 4000, Belgium

Location

CHU de Liège

Liège, 4000, Belgium

Location

Hôpital Sainte Elisabeth

Namur, 5000, Belgium

Location

Clinique Saint Pierre

Ottignies, 1340, Belgium

Location

CHR Peltzer La Tourelle

Verviers, 4800, Belgium

Location

CHRU Mont Godinne

Yvoir, Belgium

Location

CH d'Abbeville

Abbeville, 80142, France

Location

CH du Pays d'Aix

Aix-en-Provence, 13606, France

Location

CHU d'Amiens

Amiens, 80054, France

Location

CHU d'Angers

Angers, 49000, France

Location

CH Victor Dupouy

Argenteuil, 95107, France

Location

CH d'Arras

Arras, 62022, France

Location

CH d Avignon - Hopital Henri Duffaut

Avignon, 84902, France

Location

CH Côte Basque

Bayonne, 64100, France

Location

CHU Jean Minjoz

Besançon, 25030, France

Location

CH de Blois

Blois, 41000, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Polyclinique Bordeaux Nord

Bordeaux, 33300, France

Location

CH de Boulogne-sur-Mer

Boulogne-sur-Mer, 62321, France

Location

CH de Bourg en Bresse

Bourg-en-Bresse, 01000, France

Location

CHU Morvan

Brest, 29609, France

Location

CH de Brive

Brivé, 19190, France

Location

IHBN

Caen, France

Location

CH de Cannes

Cannes, 06401, France

Location

Clinique Du Parc

Castelnau-le-Lez, 34170, France

Location

Médipôle de Savoie

Challes-les-Eaux, 73191, France

Location

CHU de Châlon sur Sâone

Chalon-sur-Sâone, France

Location

CH Métropole Savoie

Chambéry, 73011, France

Location

Hôpital d'Instruction des Armées Percy

Clamart, 92141, France

Location

CHU Estaing

Clermont-Ferrand, 63000, France

Location

Pôle Santé République

Clermont-Ferrand, 63050, France

Location

CH Sud Francilien de Corbeil

Corbeil-Essonnes, 91108, France

Location

APHP - Hopital Henri Mondor

Créteil, 94010, France

Location

CHU de Dijon - Hôpital le Bocage

Dijon, 21034, France

Location

CH de Dunkerque

Dunkirk, 59385, France

Location

CH Eure Seine

Évreux, 27015, France

Location

CHU de Grenoble

Grenoble, 38000, France

Location

Institut Daniel Hollard

Grenoble, 38028, France

Location

CH Départemental de Vendée

La Roche-sur-Yon, France

Location

Hôpital St Louis

La Rochelle, 17019, France

Location

CH de Versailles - Hopital André Mignot

Le Chesnay, 78157, France

Location

Hôpital Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

CH du Mans

Le Mans, 72000, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

CHRU Lille - Hôpital Claude Huriez

Lille, 59037, France

Location

Hôpital Saint Vincent de Paul

Lille, France

Location

CHU de Limoges

Limoges, 87042, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Paoli Calmette

Marseille, 13273, France

Location

Hôpital de la conception

Marseille, 13385, France

Location

CH des Chanaux

Mâcon, 71018, France

Location

CH de Meaux

Meaux, 77104, France

Location

Hôpital de Mercy

Metz, 57038, France

Location

Centre Hospitalier Annecy Genevois

Metz-Tessy, 74374, France

Location

CHU de Montpellier

Montpellier, France

Location

CHU de Mulhouse

Mulhouse, 68070, France

Location

CHU de Nantes

Nantes, 44093, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

CHU de Nîmes

Nîmes, 30029, France

Location

CHR de la Source

Orléans, 45100, France

Location

Hopital Saint Antoine

Paris, 75012, France

Location

APHP - Hôpital Saint Louis

Paris, 75475, France

Location

Hôpital de la Pitié Salpêtrière

Paris, 75651, France

Location

APHP - Hôpital Necker

Paris, 75743, France

Location

CH de Perpigan

Perpignan, 66000, France

Location

CHU du Haut Leveque

Pessac, 33604, France

Location

Clinique Francheville

Périgueux, 24004, France

Location

CH Périgueux

Périgueux, 24019, France

Location

Chu Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU de Poitiers

Poitiers, 96021, France

Location

CH René Dubos

Pontoise, 95301, France

Location

CH de Cornouaille

Quimper, 29107, France

Location

CHU Robert Debre

Reims, 51092, France

Location

CHU de Rennes

Rennes, 35033, France

Location

CH de Roubaix

Roubaix, 59100, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

CH de Saint Brieuc

Saint-Brieuc, 22000, France

Location

Centre René Huguenin - Institut Curie

Saint-Cloud, 92210, France

Location

Groupe Hospitalier Sud Réunion

Saint-Pierre, 97448, France

Location

CH Saint Quentin

Saint-Quentin, 02321, France

Location

CHU de Saint Malo

St-Malo, 35400, France

Location

Strasbourg Oncologie Libérale

Strasbourg, 67000, France

Location

CHU de Strasbourg

Strasbourg, 67098, France

Location

CHI Toulon La Seyne-sur-mer

Toulon, 83056, France

Location

CHU Purpan - Toulouse

Toulouse, 31059, France

Location

CHRU Bretonneau

Tours, 37044, France

Location

Hôpital de Valence

Valence, 26953, France

Location

CHU de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

CH de Bretagne Atlantique

Vannes, 56017, France

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Lenalidomide; Rituximab

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Fabrice Jardin, MD,Professor

  The Lymphoma Study Association - LYSA

  PRINCIPAL INVESTIGATOR

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: April 23, 2014
• First Posted: May 1, 2014
• Study Start: August 1, 2014
• Primary Completion: November 5, 2018
• Study Completion: January 1, 2021
• Last Updated: April 13, 2021

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (14); FR (83)