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

Diffuse Large B Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02128061
• Other study ID #: SENIOR
• Status: Completed
• Phase: Phase 3
• Start date: August 2014
• Est. completion date: January 2021

Study information

• Verified date: March 2020
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: January 2021
• Est. primary completion date: November 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 80 Years and older

Eligibility

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")

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Lenalidomide

• Rituximab

Locations

Country	Name	City	State
Belgium	ZNA Stuivenberg	Antwerpen
Belgium	A. Z. Sint-Jan	Bruges
Belgium	Hôpital Erasme	Brussel
Belgium	Institut Jules Bordet	Bruxelles
Belgium	Université Catholique de Louvain Saint Luc	Bruxelles
Belgium	Grand Hôpital de Charleroi	Charleroi
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	AZ Groeninge	Kortrijk
Belgium	CHR Citadelle	Liege
Belgium	CHU de Liège	Liege
Belgium	Hôpital Sainte Elisabeth	Namur
Belgium	Clinique Saint Pierre	Ottignies
Belgium	CHR Peltzer La Tourelle	Verviers
Belgium	CHRU Mont Godinne	Yvoir
France	CH d'Abbeville	Abbeville
France	CH du Pays d'Aix	Aix-en-Provence
France	CHU d'Amiens	Amiens
France	CHU d'Angers	Angers
France	CH Victor Dupouy	Argenteuil
France	CH d'Arras	Arras
France	CH d Avignon - Hopital Henri Duffaut	Avignon
France	CH Côte Basque	Bayonne
France	CHU Jean Minjoz	Besancon
France	CH de Blois	Blois
France	Institut Bergonié	Bordeaux
France	Polyclinique Bordeaux Nord	Bordeaux
France	CH de Boulogne-sur-Mer	Boulogne-sur-mer
France	CH de Bourg en Bresse	Bourg-en-bresse
France	CHU Morvan	Brest
France	CH de Brive	Brive
France	IHBN	Caen
France	CH de Cannes	Cannes
France	Clinique Du Parc	Castelnau-le-lez
France	Médipôle de Savoie	Challes-les-Eaux
France	CHU de Châlon sur Sâone	Chalon-sur-Sâone
France	CH Métropole Savoie	Chambery
France	Hôpital d'Instruction des Armées Percy	Clamart
France	CHU Estaing	Clermont-Ferrand
France	Pôle Santé République	Clermont-Ferrand
France	CH Sud Francilien de Corbeil	Corbeil-Essonnes
France	APHP - Hopital Henri Mondor	Creteil
France	CHU de Dijon - Hôpital le Bocage	Dijon
France	CH de Dunkerque	Dunkerque
France	CH Eure Seine	Evreux
France	CHU de Grenoble	Grenoble
France	Institut Daniel Hollard	Grenoble
France	CH Départemental de Vendée	La Roche sur Yon
France	Hôpital St Louis	La Rochelle
France	CH de Versailles - Hopital André Mignot	Le Chesnay
France	Hôpital Bicêtre	Le Kremlin Bicetre
France	CH du Mans	Le Mans
France	Clinique Victor Hugo	Le Mans
France	CHRU Lille - Hôpital Claude Huriez	Lille
France	Hôpital Saint Vincent de Paul	Lille
France	CHU de Limoges	Limoges
France	Centre Léon Bérard	Lyon
France	CH des Chanaux	Macon
France	Hôpital de la conception	Marseille
France	Institut Paoli Calmette	Marseille
France	CH de Meaux	Meaux
France	Hôpital de Mercy	Metz
France	Centre Hospitalier Annecy Genevois	Metz-Tessy
France	CHU de Montpellier	Montpellier
France	CHU de Mulhouse	Mulhouse
France	CHU de Nantes	Nantes
France	Centre Antoine Lacassagne	Nice
France	CHU de Nîmes	Nimes
France	CHR de la Source	Orleans
France	APHP - Hôpital Necker	Paris
France	APHP - Hôpital Saint Louis	Paris
France	Hôpital de la Pitié Salpêtrière	Paris
France	Hopital Saint Antoine	Paris
France	CH Périgueux	Perigueux
France	Clinique Francheville	Perigueux
France	CH de Perpigan	Perpignan
France	CHU du Haut Leveque	Pessac
France	Chu Lyon Sud	Pierre-Bénite
France	CHU de Poitiers	Poitiers
France	CH René Dubos	Pontoise
France	CH de Cornouaille	Quimper
France	CHU Robert Debre	Reims
France	CHU de Rennes	Rennes
France	CH de Roubaix	Roubaix
France	Centre Henri Becquerel	Rouen
France	CHU de Saint Malo	Saint Malo
France	Groupe Hospitalier Sud Réunion	Saint Pierre
France	CH Saint Quentin	Saint Quentin
France	CH de Saint Brieuc	Saint-Brieuc
France	Centre René Huguenin - Institut Curie	Saint-Cloud
France	CHU de Strasbourg	Strasbourg
France	Strasbourg Oncologie Libérale	Strasbourg
France	CHI Toulon La Seyne-sur-mer	Toulon
France	CHU Purpan - Toulouse	Toulouse
France	CHRU Bretonneau	Tours
France	Hôpital de Valence	Valence
France	CHU de Brabois	Vandoeuvre les Nancy
France	CH de Bretagne Atlantique	Vannes

Sponsors (2)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation	Centre Henri Becquerel

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression-Free Survival (PFS)	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.	PFS rates at 2 years
Secondary	Event-Free Survival (EFS)	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.	EFS rates at 2 years
Secondary	Duration of Response (DoR)	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.	DoR rates at 2 years
Secondary	Disease-Free Survival (DFS)	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.	DFS rates at 2 years
Secondary	OS according to GCB/non-GCB phenotype	OS will be described for the R2-miniCHOP group according to Hans algorithm (GCB/non-GCB phenotype).	OS according to GCB/non-GCB phenotype rates at 2 years
Secondary	Response Rate at the end of treatment	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)).	22 weeks (28 days after the end of the 6, three-weeks interval, cycles of treatment) or within 28 days following permanent treatment discontinuation
Secondary	Simplified Geriatric Scales	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.	At baseline
Secondary	Health related Quality of Life (HRQOL)	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.	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)