Efficacy of Lenalidomide in Combination With Subcutaneous Rituximab + miniCHOP in DLBCL Patients of 80 y/o or+
- Conditions
- Diffuse Large B Cell Lymphoma
- Interventions
- Registration Number
- NCT02128061
- Lead Sponsor
- The Lymphoma Academic Research Organisation
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 250
- 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)
- 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")
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description R-miniCHOP Rituximab 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 R2-miniCHOP Lenalidomide 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 R2-miniCHOP Rituximab 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
- Primary Outcome Measures
Name Time Method The overall survival (OS) OS rates at 2 years 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.
- Secondary Outcome Measures
Name Time Method Response Rate at the end of treatment 22 weeks (28 days after the end of the 6, three-weeks interval, cycles of treatment) or within 28 days following permanent treatment discontinuation Disease response evaluation at end of treatment (after 6 cycles) will be used to determine the Response Rate. Response will be assessed at end of treatment (after end of the 6th cycle of treatment or at permanent treatment discontinuation).
Assessment of response will be based on the International Workshop to Standardize Response criteria for non-Hodgkin's lymphoma (NHL) (Criteria for evaluation of response in NHL (Cheson, 1999)).Progression-Free Survival (PFS) PFS rates at 2 years PFS is defined as the time from randomization into the study to the first observation of documented disease progression/relapse or death due to any cause. If a subject has not progressed or died, PFS will be censored at the time of last visit with adequate assessment.
Event-Free Survival (EFS) EFS rates at 2 years EFS will be measured from the date of randomization to the date of first documented disease progression/relapse (Cheson 1999), initiation of new anti-lymphoma therapy or death from any cause. Patients without documented event at the time of analysis will be censored at their visit with adequate assessment.
Duration of Response (DoR) DoR rates at 2 years DoR will be measured from the time of attainment of Complete Response/unconfirmed Complete Response (CR/CRu) or Partial Response (PR) to the date of first documented disease progression/relapse or death from any cause. Patients alive and free of progression will be censored at their last visit with adequate assessment.
Disease-Free Survival (DFS) DFS rates at 2 years DFS will be measured from the date of attainment of a complete or unconfirmed complete response (at the end of treatment or at permanent treatment discontinuation evaluation) to the date of first observation of documented disease progression or death due to any cause. Complete Response/unconfirmed Complete Response (CR/CRu) patients who have not progressed or died will be censored at the time of last visit with adequate assessment.
OS according to GCB/non-GCB phenotype OS according to GCB/non-GCB phenotype rates at 2 years OS will be described for the R2-miniCHOP group according to Hans algorithm (GCB/non-GCB phenotype).
Simplified Geriatric Scales At baseline Four geriatric tools will be performed before any chemotherapy administration (Instrumental Activities of Daily Living (IADL), Mini Nutritional Assessment (MNA), G8, and Cumulative Illness Rating Scale for Geriatrics (CIRS-G) scales). Each scale will be analyzed in order to have a picture of the population at baseline. Thereafter, the prognosis impact in OS and PFS of each scale will be evaluated using univariate (Kaplan Meier) and multivariate analyses (Cox model). Safety analyses will also be performed according to each scale in order to evaluate the toxicity predictive power of these scales.
Health related Quality of Life (HRQOL) 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) HRQOL will be assessed by the Quality of Life Questionnaire-C30 and Elderly14 (QLQ-C30 and the QLQ-ELD14) at randomization and at end of treatment. The improvement or not of the QoL will therefore be assessed.
The QLQ-ELD14 was developed to supplement the QLQ-C30 for measuring HRQoL in patients aged \>70 years in oncology studies.
Trial Locations
- Locations (97)
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
CHR Citadelle
🇧🇪Liege, Belgium
CHU d'Angers
🇫🇷Angers, France
CHU Jean Minjoz
🇫🇷Besancon, France
IHBN
🇫🇷Caen, France
Clinique Du Parc
🇫🇷Castelnau-le-lez, France
APHP - Hopital Henri Mondor
🇫🇷Creteil, France
CH Eure Seine
🇫🇷Evreux, France
CHU de Grenoble
🇫🇷Grenoble, France
CH de Meaux
🇫🇷Meaux, France
Hôpital de Mercy
🇫🇷Metz, France
Hopital Saint Antoine
🇫🇷Paris, France
Hôpital de la Pitié Salpêtrière
🇫🇷Paris, France
Hôpital Bicêtre
🇫🇷Le Kremlin Bicetre, France
AZ Groeninge
🇧🇪Kortrijk, Belgium
Institut Bergonié
🇫🇷Bordeaux, France
Polyclinique Bordeaux Nord
🇫🇷Bordeaux, France
CH Métropole Savoie
🇫🇷Chambery, France
Hôpital Saint Vincent de Paul
🇫🇷Lille, France
CHU de Nantes
🇫🇷Nantes, France
CHU de Nîmes
🇫🇷Nimes, France
APHP - Hôpital Saint Louis
🇫🇷Paris, France
CH Périgueux
🇫🇷Perigueux, France
Chu Lyon Sud
🇫🇷Pierre-Bénite, France
CHU de Poitiers
🇫🇷Poitiers, France
CH de Cornouaille
🇫🇷Quimper, France
CH de Roubaix
🇫🇷Roubaix, France
Centre Henri Becquerel
🇫🇷Rouen, France
CHU Purpan - Toulouse
🇫🇷Toulouse, France
CH de Brive
🇫🇷Brive, France
CH de Cannes
🇫🇷Cannes, France
CH Côte Basque
🇫🇷Bayonne, France
Hôpital Erasme
🇧🇪Brussel, Belgium
Université Catholique de Louvain Saint Luc
🇧🇪Bruxelles, Belgium
CH d'Abbeville
🇫🇷Abbeville, France
CH d'Arras
🇫🇷Arras, France
CH d Avignon - Hopital Henri Duffaut
🇫🇷Avignon, France
Institut Daniel Hollard
🇫🇷Grenoble, France
CH Départemental de Vendée
🇫🇷La Roche sur Yon, France
CHU de Liège
🇧🇪Liege, Belgium
CHR Peltzer La Tourelle
🇧🇪Verviers, Belgium
CHU d'Amiens
🇫🇷Amiens, France
Hôpital St Louis
🇫🇷La Rochelle, France
Clinique Francheville
🇫🇷Perigueux, France
Grand Hôpital de Charleroi
🇧🇪Charleroi, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Clinique Saint Pierre
🇧🇪Ottignies, Belgium
CHRU Mont Godinne
🇧🇪Yvoir, Belgium
CHU Estaing
🇫🇷Clermont-Ferrand, France
CHU de Dijon - Hôpital le Bocage
🇫🇷Dijon, France
CH de Dunkerque
🇫🇷Dunkerque, France
CH du Mans
🇫🇷Le Mans, France
A. Z. Sint-Jan
🇧🇪Bruges, Belgium
CH du Pays d'Aix
🇫🇷Aix-en-Provence, France
CH Victor Dupouy
🇫🇷Argenteuil, France
CH de Blois
🇫🇷Blois, France
CH de Boulogne-sur-Mer
🇫🇷Boulogne-sur-mer, France
CHU Morvan
🇫🇷Brest, France
Médipôle de Savoie
🇫🇷Challes-les-Eaux, France
Hôpital d'Instruction des Armées Percy
🇫🇷Clamart, France
Hôpital Sainte Elisabeth
🇧🇪Namur, Belgium
CH de Bourg en Bresse
🇫🇷Bourg-en-bresse, France
CHU de Châlon sur Sâone
🇫🇷Chalon-sur-Sâone, France
Pôle Santé République
🇫🇷Clermont-Ferrand, France
CH Sud Francilien de Corbeil
🇫🇷Corbeil-Essonnes, France
Hôpital de la conception
🇫🇷Marseille, France
CHU de Montpellier
🇫🇷Montpellier, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Groupe Hospitalier Sud Réunion
🇫🇷Saint Pierre, France
Centre René Huguenin - Institut Curie
🇫🇷Saint-Cloud, France
CHRU Bretonneau
🇫🇷Tours, France
CH de Bretagne Atlantique
🇫🇷Vannes, France
Centre Léon Bérard
🇫🇷Lyon, France
CH de Versailles - Hopital André Mignot
🇫🇷Le Chesnay, France
Clinique Victor Hugo
🇫🇷Le Mans, France
Centre Hospitalier Annecy Genevois
🇫🇷Metz-Tessy, France
CH René Dubos
🇫🇷Pontoise, France
CHRU Lille - Hôpital Claude Huriez
🇫🇷Lille, France
Institut Paoli Calmette
🇫🇷Marseille, France
CHU de Mulhouse
🇫🇷Mulhouse, France
CHU du Haut Leveque
🇫🇷Pessac, France
CHU de Rennes
🇫🇷Rennes, France
CHU de Saint Malo
🇫🇷Saint Malo, France
Hôpital de Valence
🇫🇷Valence, France
CHU de Brabois
🇫🇷Vandoeuvre les Nancy, France
APHP - Hôpital Necker
🇫🇷Paris, France
CHU de Limoges
🇫🇷Limoges, France
CH des Chanaux
🇫🇷Macon, France
CHR de la Source
🇫🇷Orleans, France
CHU Robert Debre
🇫🇷Reims, France
CHI Toulon La Seyne-sur-mer
🇫🇷Toulon, France
CH de Perpigan
🇫🇷Perpignan, France
CH Saint Quentin
🇫🇷Saint Quentin, France
CH de Saint Brieuc
🇫🇷Saint-Brieuc, France
Strasbourg Oncologie Libérale
🇫🇷Strasbourg, France
CHU de Strasbourg
🇫🇷Strasbourg, France