Clinical trial NCT01197560: Study of Lenalidomide to Evaluate Safety and Effectiveness in Patients With Diffuse Large B-Cell Lymphoma (DLBCL)
Official title: A Phase 2/3, Multicenter, Randomized, Open-label Study to Compare the Efficacy and Safety of Lenalidomide (Revlimid ®) Versus Investigator's Choice in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Diffuse Large B-cell Lymphoma
Keywords: Diffuse Large B-Cell Lymphoma
Non Hodgkin's Lymphoma
relapsed
refractory
relapsed/refractory
DLBCL
Diffuse Large B Cell Lymphoma
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2010-09-09
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare lenalidomide to a control drug and see which one delays Diffuse Large B-Cell Lymphoma (DLBCL) disease progression longer.

Detailed description: This research study is for patients who have been diagnosed with Diffuse Large B-cell Lymphoma (DLBCL) that did not respond to (refractory) or that has come back after chemotherapy treatment (relapsed). Lymphoma is a cancer of a type of blood cell called lymphocytes. DLBCL is just one type of lymphoma. Within DLBCL there are two different subtypes called Germinal Center B-cell (GCB) and non-GCB which can be determined by cell surface marker tests or by gene expression tests. Scientists can look at cells and genes in the laboratory and see that the two kinds are different, but they don't know yet what the difference means. To patients and doctors these two kinds seem the same. Right now doctors don't usually do tests to find out which kind a patient has because the treatment is the same for both.

This study will have two stages, 1 and 2. The main purpose of Stage 1 is to separate patients by subtype and then test whether patients taking lenalidomide or any one of four other drugs have a better response. It is possible that lenalidomide will work better than one of the other drugs in zero, one, or both subtypes. Stage 2 will further test only the subtype(s) from Stage 1 that showed a good response to lenalidomide. The main purpose of Stage 2 is to test how long patients are disease free on lenalidomide compared to one of the four other drugs.

On 29 January 2013 the enrolment goal for the Stage 1 portion of the study was met and enrollment was stopped. The final analysis for Stage 1 was performed as of the 04 Jul 2013 data cutoff date. According to the Stage 1 results as assessed by the independent response adjudication committee (IRAC), neither subtype met the pre specified requirement to be further studied in Stage 2. Additionally, a suitable assay for the selection of participants for the Stage 2 study was not available. Therefore, on 6 January 2014, Celgene decided to not open Stage 2.

Eligibility criteria: Inclusion Criteria:

* Histologically proven Diffuse Large B-Cell Lymphoma (DLBCL).
* Relapsed or refractory to combination chemotherapy for DLBCL that contains rituximab and an anthracycline, and one additional combination chemotherapy or stem cell transplant.
* Measurable DLBCL disease by computed tomograph (CT) / magnetic resonance imagining (MRI).
* Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.

Exclusion Criteria:

* Diagnosis of lymphoma histologies other than DLBCL.
* History of malignancies, other than DLBCL, unless the patient has been disease free for 3 years or more.
* Eligible for autologous stem cell transplant.
* Known seropositive for, or history of, active human immunodeficiency virus (HIV) hepatitis B virus (HBV), hepatitis C virus (HCV)
* Neuropathy grade 4.

Primary outcomes:
measure: Stage 1: Percentage of Participants With an Overall Response According to the International Working Group (IWG) Response Criteria for Non Hodgkin's Lymphoma (NHL), Cheson 1999 and Evaluated by the Independent Response Adjudication Committee (IRAC)
timeFrame: From the date of randomization to the data cut-off of 4 July 2013; when all patients reached the scheduled 16-week assessment or had progressed/died before the scheduled 16-week assessment); the median study duration was 27.0 and 19.7 weeks, respectively.
measure: Stage 1: Percentage of Participants With an Overall Response According to the IWG Response Criteria Based on the Investigators Assessment at the Final Data Cut During the Core Treatment Phase
timeFrame: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Events (TEAEs) in the Overall Treatment Phase by Initial Treatment Assignment
timeFrame: From first dose of study drug to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
measure: Stage 2: Overall Response Rate (ORR)
timeFrame: Approximately 3.5 years
measure: Stage 2: Duration of Response (DoR)
timeFrame: Approximately 3.5 years
measure: Stage 2: Overall Survival (OS)
timeFrame: Approximately 3.5 years
measure: Stage 2: Duration of Complete Response
timeFrame: Approximately 3.5 years
measure: Stage 2: Overall Response Rate for With a Duration of Response Lasting ≥ 16 Weeks
timeFrame: Approximately 3.5 years
measure: Stage 2: Time to Progression
timeFrame: Approximately 3.5 years
measure: Stage 2: Health Related Quality of Life Questionnaires
timeFrame: Approximately 3.5 years
Other outcomes:
measure: Stage 1: Percentage of Participants With a Durable Overall Response (dORR) According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase
timeFrame: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
measure: Stage 1: Percentage of Participants With a Complete Response According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase
timeFrame: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
measure: Stage 1: Kaplan Meier Estimates of Duration of Overall Response (DoR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase
timeFrame: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
measure: Stage 1: Kaplan Meier Estimates of Duration of Complete Response (DoCR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase
timeFrame: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
measure: Stage 1: Kaplan Meier Estimates of Progression-Free Survival As Assessed By The Investigators At The Final Data Cut During The Core Treatment Phase
timeFrame: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
measure: Stage 1: Kaplan Meier Estimates of Overall Survival As Assessed by the Investigators at the Final Data Cut During The Core Treatment Phase
timeFrame: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
measure: Stage 2: Progression-Free Survival
timeFrame: Approximately 3.5 years
Locations:
city: Burbank
country: United States
facility: Providence St Joseph Medical Center/Cancer Center
state: California
city: Orlando
country: United States
facility: MD Anderson Cancer Center Orlando
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan, Comprehensive Cancer Center
state: Michigan
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University Siteman Cancer Center
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Houston
state: Texas
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Herston
country: Australia
facility: Royal Brisbaine and Womens Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Innsbruck
country: Austria
facility: Innsbruck University Hospital
city: Salzburg
country: Austria
facility: Universitätsklinikum Salzburg
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Hradec Kralove 5
country: Czechia
facility: University Hospital Hradec Kralove
city: Praha
country: Czechia
facility: Charles University
city: Brest Cedex 2
country: France
facility: ICH CHU Brest- C.H.U. MORAVAN
city: Grenoble
country: France
facility: CHU de Grenoble-Hopital Albert Michallon
city: La Roche Sur Yon
country: France
facility: Chd -Vendee
city: Lyon
country: France
facility: Centre Hospitalier Lyon Sud
city: Marsielle
country: France
facility: Institute Paoli-Calmette
city: Nantes Cedex 1
country: France
facility: Hotel Dieu
city: Perpignan
country: France
facility: Hôpital Saint Jean
city: Pessac
country: France
facility: CHRU-Hopital du Haut -Leveque
city: Rennes
country: France
facility: CHU de Rennes Hopital de Pontchaillou
city: Toulouse
country: France
facility: University Hospital OF Toulouse Purpan
city: Vandoeuvre-les Nancy cedex
country: France
facility: Hopital de Brabois Adultes
city: Bologna
country: Italy
facility: Istituto di Ematologica Istituto di Ematologica " L.e. A. Seragnoli' Azienda Ospedaliera Universitaria Policlinico
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Genova
country: Italy
facility: Clinica Ematologica, A.O.U. San Martino di Genova
city: Miano
country: Italy
facility: IEO istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Universita Federico II di Napoli Nuovo Policlinico
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Rionero In Vulture (PZ)
country: Italy
facility: Irccs/Crob
city: Roma
country: Italy
facility: Policlinico Tor Vergata (Universta Tor Vergata)
city: Terni
country: Italy
facility: Azienda Ospedaliera di Perugai Ospedale S. Maria della Miseri
city: Barcelona
country: Spain
facility: Hospital Universitari Vll D' Hebron
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Marbella
country: Spain
facility: Hospital Costa Del Sol
city: Ourense
country: Spain
facility: CH de Orense
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Salamanca
country: Spain
facility: Hosptial Clinico Universitario de Salamanca
city: Umea
country: Sweden
facility: Onkologiska kliniken
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital Haematology
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital Haematology Department
city: Leeds
country: United Kingdom
facility: St. James Institute of Oncology
city: London
country: United Kingdom
facility: Royal Mardsen Hospital - Fulham (Satellite Site)
city: Manchester
country: United Kingdom
facility: The Christie Foundation Trust, I'st Floor, Haemotology Oncology Outpatients, Lymphoma Team
city: Plymouth
country: United Kingdom
facility: Derrford Hospital
city: Southhampton
country: United Kingdom
facility: Southhampton University Hospital NHS Trust
city: Sutton
country: United Kingdom
facility: Royal Mardsen NHS Foundation Trust
Study officials:
affiliation: Celgene Corporation
name: Adrian Kilcoyne, MD
role: STUDY_DIRECTOR
References:
citation: Czuczman MS, Trneny M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A Phase 2/3 Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Lenalidomide Versus Investigator's Choice in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. doi: 10.1158/1078-0432.CCR-16-2818. Epub 2017 Apr 5.
citation: Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL, Pileri SA, Malik F, Macon WR, Goy A, Witzig TE, Czuczman MS. Higher response to lenalidomide in relapsed/refractory diffuse large B-cell lymphoma in nongerminal center B-cell-like than in germinal center B-cell-like phenotype. Cancer. 2011 Nov 15;117(22):5058-66. doi: 10.1002/cncr.26135. Epub 2011 Apr 14.