Study of Lenalidomide to Evaluate Safety and Effectiveness in Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

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ClinicalTrials.gov Identifier: NCT01197560

Recruitment Status : Active, not recruiting

First Posted : September 9, 2010

Results First Posted : August 20, 2014

Last Update Posted : January 19, 2018

Sponsor:

Information provided by (Responsible Party):

Celgene

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Diffuse Large B-cell Lymphoma	Drug: Lenalidomide Drug: Gemcitabine Drug: Oxaliplatin Drug: Rituximab Drug: Etoposide	Phase 2 Phase 3

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.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	111 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Actual Study Start Date :	September 1, 2010
Actual Primary Completion Date :	July 4, 2013
Estimated Study Completion Date :	March 4, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Drug Information available for: Lenalidomide

Genetic and Rare Diseases Information Center resources: B-cell Lymphoma Lymphosarcoma Diffuse Large B-Cell Lymphoma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Lenalidomide	Drug: Lenalidomide Lenalidomide 25 mg orally for 21/28 days until Diffuse Large B-Cell Lymphoma (DLBCL) progressive disease. For patients with Creatinine Clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg (max escalation is 15 mg).
Active Comparator: Investigators Choice One of the following: Lenalidomide, Gemcitabine, Oxaliplatin, Rituximab, or Etoposide	Drug: Gemcitabine Suggested starting doses and regimens for Gemcitabine is 1,250 mg/m2 IV days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m2 IV days 1 and 15 every 28 days for 6 Cycles Drug: Oxaliplatin Suggested starting dose and regimen for Oxaliplatin is 100 mg/m2 IV day 1 for 21 days for 6 Cycles Drug: Rituximab Suggested starting dose for Rituximab is 375 mg/m2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Drug: Etoposide Suggested starting doses for Etoposide are: 100 mg/m2 IV days 1-5 every 28 days for 6 Cycles, or 100 mg/m2 IV days 1-3 every 28 days for 6 Cycles, or 50 mg/m2 oral days 1-21 every 28 days for 6 Cycles, or 50 mg/m2 oral days 1-14 every 28 days for 6 Cycles, or 50 mg/m2 oral days 1-10 every 28 days for 6 Cycles

Arm

Intervention/treatment

Experimental: Lenalidomide

Drug: Lenalidomide

Lenalidomide 25 mg orally for 21/28 days until Diffuse Large B-Cell Lymphoma (DLBCL) progressive disease. For patients with Creatinine Clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg (max escalation is 15 mg).

Active Comparator: Investigators Choice

One of the following:

Lenalidomide, Gemcitabine, Oxaliplatin, Rituximab, or Etoposide

Drug: Gemcitabine

Suggested starting doses and regimens for Gemcitabine is 1,250 mg/m2 IV days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m2 IV days 1 and 15 every 28 days for 6 Cycles

Drug: Oxaliplatin

Suggested starting dose and regimen for Oxaliplatin is 100 mg/m2 IV day 1 for 21 days for 6 Cycles

Drug: Rituximab

Suggested starting dose for Rituximab is 375 mg/m2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only)

Drug: Etoposide

Suggested starting doses for Etoposide are:

100 mg/m2 IV days 1-5 every 28 days for 6 Cycles, or 100 mg/m2 IV days 1-3 every 28 days for 6 Cycles, or 50 mg/m2 oral days 1-21 every 28 days for 6 Cycles, or 50 mg/m2 oral days 1-14 every 28 days for 6 Cycles, or 50 mg/m2 oral days 1-10 every 28 days for 6 Cycles

Outcome Measures

Primary Outcome Measures :

Stage 1: Percentage of Participants With an Overall Response Rate (ORR) According to the International Working Group (IWG) Response Criteria for Non Hodgkin's Lymphoma (NHL), Cheson 1999. [ Time Frame: From Sept 2010 to the data cut-off of 4 July 2013; when all participants had reached the scheduled 16-week assessment or had progressed/died before the scheduled 16-week assessment). Median follow-up time was 6.7 and 4.7 months in each arm respectively ]
Response was defined as participants with a complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on IWG 1999 Response Criteria for NHL as evaluated by the Independent Response Adjudication Committee (IRAC).

Complete Response (CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers.

CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.

Partial Response (PR) is a 50% decrease in the sum of the products of diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes
Stage 2: Progression-free Survival for Diffuse Large B-Cell Lymphoma (DLBCL) Participants
Number of participants who survive without progressing based on the International Working Group Response Criteria [IWG].

Secondary Outcome Measures :

Stage 2: Complete Response Rate for Diffuse Large B-Cell Lymphoma (DLBCL) Participants
Complete Response Rate (CR + CRu rate) was to be calculated as the proportion of participants achieving a CR or CRu using 1999 IWG Response Criteria, (Cheson, 1999).

CR: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities.

Cru: Criteria for CR above but with 1 or more of the following:

A residual lymph node mass > 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of diameters (SPD) Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia).
Stage 2: Overall Response Rate for Diffuse Large B-Cell Lymphoma (DLBCL) Participants
Response was defined as participants with a complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on IWG 1999 Response Criteria for NHL (Cheson1999) as evaluated by the Independent Response Assessment Committee (IRAC).

Complete Response (CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers.

CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.

Partial Response (PR) is a 50% decrease in the sum of the products of diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes
Stage 2: Duration of Overall Response for Diffuse Large B-Cell Lymphoma (DLBCL) Participants [ Time Frame: Approximately 3.5 years ]
Length of time of overall response (Complete Response + Complete Response unconfirmed + Partial Response) was to be calculated for responders as the time from documented initial response (either CR, CRu, or PR) until documented disease progression determined by CT or MRI scan, or death, whichever occurs earlier.
Stage 2: Overall Survival (OS) for Diffuse Large B-Cell Lymphoma (DLBCL) Participants
Overall Survival (OS) is defined as the time from randomization until death due to any cause.
Stage 2: Duration of Complete Response for Diffuse Large B-Cell Lymphoma (DLBCL) Participants
Duration of Complete Response was to be calculated for complete responders as the time of from documented initial complete response (either CR or CRu) until documented disease progression determined by CT or MRI scan, or death, whichever occurs earlier.
Stage 2: Overall Response Rate for Diffuse Large B-Cell Lymphoma (DLBCL) Patients With a Duration of Response Lasting ≥ 16 Weeks
Response was defined as participants with a complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on IWG Response Criteria for NHL (Cheson1999) as evaluated by the Independent Response Assessment Committee (IRAC).

Complete Response (CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers.

CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.

Partial Response (PR) is a 50% decrease in the sum of the products of diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes
Stage 2: Time to Progression for Diffuse Large B-Cell Lymphoma (DLBCL) Participants
Time to progression is defined as the time from the start of study drug therapy to the first documentation of disease progression
Stage 2: Health Related Quality of Life for Diffuse Large B-Cell Lymphoma (DLBCL) Patients
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) is a 30-item oncology-specific questionnaire developed to assess the quality of life of cancer patients. The descriptive system EQ-5D is a generic questionnaire consisting of 3 levels within each of the 5 domains. It's is a standardized instrument for use as a measure of health outcome and provides a simple descriptive profile and a single index value for health status

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01197560

Hide Study Locations

Locations


United States, California
Providence St Joseph Medical Center/Cancer Center
Burbank, California, United States, 91505
United States, Florida
MD Anderson Cancer Center Orlando
Orlando, Florida, United States, 32806
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Michigan
University of Michigan, Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48105
United States, Mississippi
Hattiesburg Clinic
Hattiesburg, Mississippi, United States, 39402
United States, Missouri
Washington University Siteman Cancer Center
Saint Louis, Missouri, United States, 63110
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, South Dakota
Avera Cancer Institute
Sioux Falls, South Dakota, United States, 57105
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
MD Anderson Houston
Houston, Texas, United States, 77030
Australia
Royal Adelaide Hospital
Adelaide, Australia, 5000
Royal Brisbaine and Womens Hospital
Herston, Australia, 4029
Princess Alexandra Hospital
Woolloongabba, Australia, 4102
Austria
Innsbruck University Hospital
Innsbruck, Austria, A6020
Universitätsklinikum Salzburg
Salzburg, Austria, A-5020
Medical University of Vienna
Vienna, Austria, A-1090
Czechia
University Hospital Hradec Kralove
Hradec Kralove 5, Czechia, 5005
Charles University
Praha, Czechia, 12808
France
ICH CHU Brest- C.H.U. MORAVAN
Brest Cedex 2, France, 29609
CHU de Grenoble-Hopital Albert Michallon
Grenoble, France, 38043
Chd -Vendee
La Roche Sur Yon, France, 85205
Centre Hospitalier Lyon Sud
Lyon, France, 69495
Institute Paoli-Calmette
Marsielle, France, 13009
Hotel Dieu
Nantes Cedex 1, France, 44903
Hôpital Saint Jean
Perpignan, France, 66046
CHRU-Hopital du Haut -Leveque
Pessac, France, 33604
CHU de Rennes Hopital de Pontchaillou
Rennes, France, 35033
University Hospital OF Toulouse Purpan
Toulouse, France, 31059
Hopital de Brabois Adultes
Vandoeuvre-les Nancy cedex, France, 54511
Italy
Istituto di Ematologica Istituto di Ematologica " L.e. A. Seragnoli' Azienda Ospedaliera Universitaria Policlinico
Bologna, Italy, 40138
Azienda Ospedaliera Universitaria Careggi
Firenze, Italy, 50141
Clinica Ematologica, A.O.U. San Martino di Genova
Genova, Italy, 16132
IEO istituto Europeo di Oncologia
Miano, Italy, 201401
Universita Federico II di Napoli Nuovo Policlinico
Napoli, Italy, 80131
Fondazione IRCCS Policlinico San Matteo
Pavia, Italy, 27100
Irccs/Crob
Rionero In Vulture (PZ), Italy, 85208
Policlinico Tor Vergata (Universta Tor Vergata)
Roma, Italy, 00133
Azienda Ospedaliera di Perugai Ospedale S. Maria della Miseri
Terni, Italy, 6156
Spain
Hospital Universitari Vll D' Hebron
Barcelona, Spain, 8035
Hospital Universitario Reina Sofia
Cordoba, Spain, 14004
Hospital Costa Del Sol
Marbella, Spain, 29600
CH de Orense
Ourense, Spain, 32005
Complejo Hospitalario de Navarra
Pamplona, Spain, 31008
Hosptial Clinico Universitario de Salamanca
Salamanca, Spain, 37007
Sweden
Onkologiska kliniken
Umea, Sweden, 90185
Akademiska Sjukhuset
Uppsala, Sweden, 75185
United Kingdom
Royal Bournemouth Hospital Haematology
Bournemouth, United Kingdom, BH7 7DW
Royal Devon and Exeter Hospital Haematology Department
Exeter, United Kingdom, EX2 5DW
St. James Institute of Oncology
Leeds, United Kingdom, LS9 7TF
Royal Mardsen Hospital - Fulham (Satellite Site)
London, United Kingdom, SW3 6U
The Christie Foundation Trust, I'st Floor, Haemotology Oncology Outpatients, Lymphoma Team
Manchester, United Kingdom, M20 4BX
Derrford Hospital
Plymouth, United Kingdom, PL6 8DH
Southhampton University Hospital NHS Trust
Southhampton, United Kingdom, SO16 6YD
Royal Mardsen NHS Foundation Trust
Sutton, United Kingdom, SM2 SPT

Sponsors and Collaborators

Celgene

Investigators


Study Director:	Adrian Kilcoyne, MD	Celgene Corporation

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.


Responsible Party:	Celgene
ClinicalTrials.gov Identifier:	NCT01197560 History of Changes
Other Study ID Numbers:	CC-5013-DLC-001
First Posted:	September 9, 2010 Key Record Dates
Results First Posted:	August 20, 2014
Last Update Posted:	January 19, 2018
Last Verified:	December 2017

Keywords provided by Celgene:


Diffuse Large B-Cell Lymphoma Non Hodgkin's Lymphoma relapsed refractory	relapsed/refractory DLBCL Diffuse Large B Cell Lymphoma

Additional relevant MeSH terms:


Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Gemcitabine Etoposide Thalidomide Oxaliplatin Lenalidomide	Etoposide phosphate Rituximab Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents

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