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

NCT ID: NCT01197560

Last Updated: 2019-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 111 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-02
• Study Completion Date: 2018-04-05

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.

Conditions

Diffuse Large B-cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lenalidomide

Lenalidomide 25 mg capsules by mouth on days 1-21 of each 28 day cycle. For patients with Creatinine Clearance ≥ 30 mL/min but \< 60 mL/min, lenalidomide 10 mg (max escalation is 15 mg).

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

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).

Investigators Choice

One of the following:

Gemcitabine, Oxaliplatin, Rituximab, or Etoposide

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

Suggested starting doses and regimens for Gemcitabine is 1,250 mg/m\^2 intravenous (IV) administration on days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m\^2 IV days 1 and 15 every 28 days for 6 Cycles

Oxaliplatin

Intervention Type: DRUG

Suggested starting dose and regimen for Oxaliplatin is 100 mg/m\^2 IV day 1 for 21 days for 6 Cycles

Rituximab

Intervention Type: DRUG

Suggested starting dose for Rituximab is 375 mg/m\^2 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)

Etoposide

Intervention Type: DRUG

Suggested starting doses for Etoposide are:

100 mg/m^2 IV days 1-5 every 28 days for 6 Cycles, or 100 mg/m^2 IV days 1-3 every 28 days for 6 Cycles, or 50 mg/m^2 oral days 1-21 every 28 days for 6 Cycles, or 50 mg/m^2 oral days 1-14 every 28 days for 6 Cycles, or 50 mg/m^2 oral days 1-10 every 28 days for 6 Cycles

Interventions

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).

Intervention Type: DRUG

Gemcitabine

Suggested starting doses and regimens for Gemcitabine is 1,250 mg/m\^2 intravenous (IV) administration on days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m\^2 IV days 1 and 15 every 28 days for 6 Cycles

Intervention Type: DRUG

Oxaliplatin

Suggested starting dose and regimen for Oxaliplatin is 100 mg/m\^2 IV day 1 for 21 days for 6 Cycles

Intervention Type: DRUG

Rituximab

Suggested starting dose for Rituximab is 375 mg/m\^2 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)

Intervention Type: DRUG

Etoposide

Suggested starting doses for Etoposide are:

100 mg/m^2 IV days 1-5 every 28 days for 6 Cycles, or 100 mg/m^2 IV days 1-3 every 28 days for 6 Cycles, or 50 mg/m^2 oral days 1-21 every 28 days for 6 Cycles, or 50 mg/m^2 oral days 1-14 every 28 days for 6 Cycles, or 50 mg/m^2 oral days 1-10 every 28 days for 6 Cycles

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adrian Kilcoyne, MD

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

Providence St Joseph Medical Center/Cancer Center

Burbank, California, United States

MD Anderson Cancer Center Orlando

Orlando, Florida, United States

Emory University

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

University of Michigan, Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Hattiesburg Clinic

Hattiesburg, Mississippi, United States

Washington University Siteman Cancer Center

St Louis, Missouri, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

MD Anderson Houston

Houston, Texas, United States

Royal Adelaide Hospital

Adelaide, , Australia

Royal Brisbaine and Womens Hospital

Herston, , Australia

Princess Alexandra Hospital

Woolloongabba, , Australia

Innsbruck University Hospital

Innsbruck, , Austria

Universitätsklinikum Salzburg

Salzburg, , Austria

Medical University of Vienna

Vienna, , Austria

University Hospital Hradec Kralove

Hradec Králové, , Czechia

Charles University

Prague, , Czechia

ICH CHU Brest- C.H.U. MORAVAN

Brest, , France

CHU de Grenoble-Hopital Albert Michallon

Grenoble, , France

Chd -Vendee

La Roche-sur-Yon, , France

Centre Hospitalier Lyon Sud

Lyon, , France

Institute Paoli-Calmette

Marsielle, , France

Hotel Dieu

Nantes, , France

Hôpital Saint Jean

Perpignan, , France

CHRU-Hopital du Haut -Leveque

Pessac, , France

CHU de Rennes Hopital de Pontchaillou

Rennes, , France

University Hospital OF Toulouse Purpan

Toulouse, , France

Hopital de Brabois Adultes

Vandœuvre-lès-Nancy, , France

Istituto di Ematologica Istituto di Ematologica " L.e. A. Seragnoli' Azienda Ospedaliera Universitaria Policlinico

Bologna, , Italy

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

Clinica Ematologica, A.O.U. San Martino di Genova

Genova, , Italy

IEO istituto Europeo di Oncologia

Miano, , Italy

Universita Federico II di Napoli Nuovo Policlinico

Napoli, , Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Irccs/Crob

Rionero in Vulture (PZ), , Italy

Policlinico Tor Vergata (Universta Tor Vergata)

Roma, , Italy

Azienda Ospedaliera di Perugai Ospedale S. Maria della Miseri

Terni, , Italy

Hospital Universitari Vll D' Hebron

Barcelona, , Spain

Hospital Universitario Reina Sofia

Córdoba, , Spain

Hospital Costa Del Sol

Marbella, , Spain

CH de Orense

Ourense, , Spain

Complejo Hospitalario de Navarra

Pamplona, , Spain

Hosptial Clinico Universitario de Salamanca

Salamanca, , Spain

Onkologiska kliniken

Umeå, , Sweden

Akademiska Sjukhuset

Uppsala, , Sweden

Royal Bournemouth Hospital Haematology

Bournemouth, , United Kingdom

Royal Devon and Exeter Hospital Haematology Department

Exeter, , United Kingdom

St. James Institute of Oncology

Leeds, , United Kingdom

Royal Mardsen Hospital - Fulham (Satellite Site)

London, , United Kingdom

The Christie Foundation Trust, I'st Floor, Haemotology Oncology Outpatients, Lymphoma Team

Manchester, , United Kingdom

Derrford Hospital

Plymouth, , United Kingdom

Southhampton University Hospital NHS Trust

Southhampton, , United Kingdom

Royal Mardsen NHS Foundation Trust

Sutton, , United Kingdom

Countries

United States; Australia; Austria; Czechia; France; Italy; Spain; Sweden; United Kingdom

References

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.

Reference Type: RESULT

PMID: 28381416 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21495023 (View on PubMed)

Other Identifiers

CC-5013-DLC-001

Identifier Type: -

Identifier Source: org_study_id