Clinical trial NCT02128061: Efficacy of Lenalidomide in Combination With Subcutaneous Rituximab + miniCHOP in DLBCL Patients of 80 y/o or+
Official title: Sub-cutaneous Rituximab-miniCHOP Versus Sub-cutaneous Rituximab-miniCHOP + Lenalidomide (R2-miniCHOP) in Diffuse Large B Cell Lymphoma for Patients of 80 Years Old or More. A Multicentric Phase III Study of the LYSA Association
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diffuse Large B Cell Lymphoma
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
Collaborators: name: Centre Henri Becquerel
First posted: 2014-05-01
Enrollment: 250
Sex: ALL
Minimum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed description: 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).

Primary endpoint of the study is to compare the efficacy of R2-miniCHOP (Sub-cutaneous Rituximab-miniCHOP + lenalidomide) and R-miniCHOP ((Sub-cutaneous Rituximab-miniCHOP) in patients of 80 years old or more with not previously treated CD20+ diffuse large B-cell lymphoma as measured by the overall survival (OS).

Secondary endpoints are:

* To evaluate the efficacy and the safety of R2-miniCHOP as measured by the PFS (Progression Free Survival), EFS (Event Free Survival), the DoR (duration of response), the DFS (disease free survival), response rate at the end of the treatment, the additional toxicities
* To evaluate the simplified scale prognostic impact (IADL, MNA, G8, CIRS-G)
* To assess the quality of life before and after treatment This study is a multicentric, phase III, open-label, randomized (1:1) trial evaluating the efficacy of R2-miniCHOP in patients aged of 80 years or more with non-previously treated CD20+ diffuse large B-cell lymphoma (age-adjusted IPI= 0 to 3), Ann Arbor stage II to IV with a performance status ECOG from 0 to 2.

This study includes a run in phase to assess feasibility, safety and tolerance of subcutaneous rituximab injections and oral lenalidomide (10 mg D1-D14) in combination with dose-reduced intensity CHOP regimen.

Eligibility criteria: Inclusion Criteria:

* 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
* Negative HIV, HBV and HCV serologies test within 4 weeks before inclusion (except after hepatitis B vaccination or for patients who are HBs Ag negative, anti-HBs positive and/or anti-HBc positive but viral DNA negative)
* 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)

Exclusion Criteria:

* 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)
* History of deep venous thrombosis or arterial thromboembolism events within the past 12 months before inclusion
* 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
* Adult patient under tutelage
* Female of childbearing potential are excluded. (Note: Females are defined as not of childbearing potential if there is documentation of "natural menopause for at least 24 consecutive months, a hysterectomy or bilateral oophorectomy")

Primary outcomes:
measure: The overall survival (OS)
timeFrame: OS rates at 2 years
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: PFS rates at 2 years
measure: Event-Free Survival (EFS)
timeFrame: EFS rates at 2 years
measure: Duration of Response (DoR)
timeFrame: DoR rates at 2 years
measure: Disease-Free Survival (DFS)
timeFrame: DFS rates at 2 years
measure: OS according to GCB/non-GCB phenotype
timeFrame: OS according to GCB/non-GCB phenotype rates at 2 years
measure: Response Rate at the end of treatment
timeFrame: 22 weeks (28 days after the end of the 6, three-weeks interval, cycles of treatment) or within 28 days following permanent treatment discontinuation
measure: Simplified Geriatric Scales
timeFrame: At baseline
measure: Health related Quality of Life (HRQOL)
timeFrame: At randomization and 22 weeks after Day 1 of Cycle 1 of R-miniCHOP or R2-miniCHOP (28 days after the end of the 6, three-weeks interval, cycles of treatment)
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Bruges
country: Belgium
facility: A. Z. Sint-Jan
city: Brussel
country: Belgium
facility: Hôpital Erasme
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Bruxelles
country: Belgium
facility: Université Catholique de Louvain Saint Luc
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Liege
country: Belgium
facility: CHR Citadelle
city: Liege
country: Belgium
facility: CHU de Liège
city: Namur
country: Belgium
facility: Hôpital Sainte Elisabeth
city: Ottignies
country: Belgium
facility: Clinique Saint Pierre
city: Verviers
country: Belgium
facility: CHR Peltzer La Tourelle
city: Yvoir
country: Belgium
facility: CHRU Mont Godinne
city: Abbeville
country: France
facility: CH d'Abbeville
city: Aix-en-Provence
country: France
facility: CH du Pays d'Aix
city: Amiens
country: France
facility: CHU d'Amiens
city: Angers
country: France
facility: CHU d'Angers
city: Argenteuil
country: France
facility: CH Victor Dupouy
city: Arras
country: France
facility: CH d'Arras
city: Avignon
country: France
facility: CH d Avignon - Hopital Henri Duffaut
city: Bayonne
country: France
facility: CH Côte Basque
city: Besancon
country: France
facility: CHU Jean Minjoz
city: Blois
country: France
facility: CH de Blois
city: Bordeaux
country: France
facility: Institut Bergonié
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord
city: Boulogne-sur-mer
country: France
facility: CH de Boulogne-sur-Mer
city: Bourg-en-bresse
country: France
facility: CH de Bourg en Bresse
city: Brest
country: France
facility: CHU Morvan
city: Brive
country: France
facility: CH de Brive
city: Caen
country: France
facility: IHBN
city: Cannes
country: France
facility: CH de Cannes
city: Castelnau-le-lez
country: France
facility: Clinique Du Parc
city: Challes-les-Eaux
country: France
facility: Médipôle de Savoie
city: Chalon-sur-Sâone
country: France
facility: CHU de Châlon sur Sâone
city: Chambery
country: France
facility: CH Métropole Savoie
city: Clamart
country: France
facility: Hôpital d'Instruction des Armées Percy
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Clermont-Ferrand
country: France
facility: Pôle Santé République
city: Corbeil-Essonnes
country: France
facility: CH Sud Francilien de Corbeil
city: Creteil
country: France
facility: APHP - Hopital Henri Mondor
city: Dijon
country: France
facility: CHU de Dijon - Hôpital le Bocage
city: Dunkerque
country: France
facility: CH de Dunkerque
city: Evreux
country: France
facility: CH Eure Seine
city: Grenoble
country: France
facility: CHU de Grenoble
city: Grenoble
country: France
facility: Institut Daniel Hollard
city: La Roche sur Yon
country: France
facility: CH Départemental de Vendée
city: La Rochelle
country: France
facility: Hôpital St Louis
city: Le Chesnay
country: France
facility: CH de Versailles - Hopital André Mignot
city: Le Kremlin Bicetre
country: France
facility: Hôpital Bicêtre
city: Le Mans
country: France
facility: CH du Mans
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lille
country: France
facility: CHRU Lille - Hôpital Claude Huriez
city: Lille
country: France
facility: Hôpital Saint Vincent de Paul
city: Limoges
country: France
facility: CHU de Limoges
city: Lyon
country: France
facility: Centre Léon Bérard
city: Macon
country: France
facility: CH des Chanaux
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Marseille
country: France
facility: Hôpital de la conception
city: Meaux
country: France
facility: CH de Meaux
city: Metz-Tessy
country: France
facility: Centre Hospitalier Annecy Genevois
city: Metz
country: France
facility: Hôpital de Mercy
city: Montpellier
country: France
facility: CHU de Montpellier
city: Mulhouse
country: France
facility: CHU de Mulhouse
city: Nantes
country: France
facility: CHU de Nantes
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nimes
country: France
facility: CHU de Nîmes
city: Orleans
country: France
facility: CHR de la Source
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: APHP - Hôpital Saint Louis
city: Paris
country: France
facility: Hôpital de la Pitié Salpêtrière
city: Paris
country: France
facility: APHP - Hôpital Necker
city: Perigueux
country: France
facility: Clinique Francheville
city: Perigueux
country: France
facility: CH Périgueux
city: Perpignan
country: France
facility: CH de Perpigan
city: Pessac
country: France
facility: CHU du Haut Leveque
city: Pierre-Bénite
country: France
facility: Chu Lyon Sud
city: Poitiers
country: France
facility: CHU de Poitiers
city: Pontoise
country: France
facility: CH René Dubos
city: Quimper
country: France
facility: CH de Cornouaille
city: Reims
country: France
facility: CHU Robert Debre
city: Rennes
country: France
facility: CHU de Rennes
city: Roubaix
country: France
facility: CH de Roubaix
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Malo
country: France
facility: CHU de Saint Malo
city: Saint Pierre
country: France
facility: Groupe Hospitalier Sud Réunion
city: Saint Quentin
country: France
facility: CH Saint Quentin
city: Saint-Brieuc
country: France
facility: CH de Saint Brieuc
city: Saint-Cloud
country: France
facility: Centre René Huguenin - Institut Curie
city: Strasbourg
country: France
facility: Strasbourg Oncologie Libérale
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Toulon
country: France
facility: CHI Toulon La Seyne-sur-mer
city: Toulouse
country: France
facility: CHU Purpan - Toulouse
city: Tours
country: France
facility: CHRU Bretonneau
city: Valence
country: France
facility: Hôpital de Valence
city: Vandoeuvre les Nancy
country: France
facility: CHU de Brabois
city: Vannes
country: France
facility: CH de Bretagne Atlantique
Study officials:
affiliation: The Lymphoma Study Association - LYSA
name: Fabrice Jardin, MD,Professor
role: PRINCIPAL_INVESTIGATOR
References: