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

NCT01197560 | Completed Phase 2 Results DMC

• 1 other identifier: CC-5013-DLC-001
• Study Type: interventional
• Target: 111
• Locations: 8 countries
• Sites: 54

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.

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

Outcome Measures

Primary Outcomes (2)

• 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)

  An overall response is a complete response (CR), unconfirmed complete response (CRu) or partial response (PR) and was evaluated by the IRAC. A CR = complete disappearance of disease and related symptoms. Lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and \> 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on exam, normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or for single nodules, in the greatest transverse diameter;no new disease.

  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.

• 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

  Response was defined as having a CR, CRu or PR, based on IWG 1999 Response Criteria for NHL as evaluated by the investigators. CR = complete disappearance of disease and disease related symptoms. All lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and \> 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on physical exam, normal size by imaging, and absence of nodules related to lymphoma. If BM was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in the other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. No new disease.

  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 (8)

• Number of Participants With Treatment Emergent Events (TEAEs) in the Overall Treatment Phase by Initial Treatment Assignment

  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.

• Stage 2: Overall Response Rate (ORR)

  Approximately 3.5 years

• Stage 2: Duration of Response (DoR)

  Approximately 3.5 years

• Stage 2: Overall Survival (OS)

  Approximately 3.5 years

• Stage 2: Duration of Complete Response

  Approximately 3.5 years

Other Outcomes (7)

• 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

  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.

• 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

  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.

• 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

  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.

Study Arms (2)

Lenalidomide

EXPERIMENTAL

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).

Drug: Lenalidomide

Investigators Choice

ACTIVE COMPARATOR

One of the following: Gemcitabine, Oxaliplatin, Rituximab, or Etoposide

Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Rituximab; Drug: Etoposide

Interventions

Lenalidomide 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).

Lenalidomide

Gemcitabine 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

Investigators Choice

Oxaliplatin DRUG

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

Investigators Choice

Rituximab 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)

Investigators Choice

Etoposide 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

Investigators Choice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celgene: lead

Study Sites (57)

Providence St Joseph Medical Center/Cancer Center

Burbank, California, 91505, United States

Location

MD Anderson Cancer Center Orlando

Orlando, Florida, 32806, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

University of Michigan, Comprehensive Cancer Center

Ann Arbor, Michigan, 48105, United States

Location

Hattiesburg Clinic

Hattiesburg, Mississippi, 39402, United States

Location

Washington University Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Houston

Houston, Texas, 77030, United States

Location

Royal Adelaide Hospital

Adelaide, 5000, Australia

Location

Royal Brisbaine and Womens Hospital

Herston, 4029, Australia

Location

Princess Alexandra Hospital

Woolloongabba, 4102, Australia

Location

Innsbruck University Hospital

Innsbruck, A6020, Austria

Location

Universitätsklinikum Salzburg

Salzburg, A-5020, Austria

Location

Medical University of Vienna

Vienna, A-1090, Austria

Location

University Hospital Hradec Kralove

Hradec Králové, 5005, Czechia

Location

Charles University

Prague, 12808, Czechia

Location

ICH CHU Brest- C.H.U. MORAVAN

Brest, 29609, France

Location

CHU de Grenoble-Hopital Albert Michallon

Grenoble, 38043, France

Location

Chd -Vendee

La Roche-sur-Yon, 85205, France

Location

Centre Hospitalier Lyon Sud

Lyon, 69495, France

Location

Institute Paoli-Calmette

Marsielle, 13009, France

Location

Hotel Dieu

Nantes, 44903, France

Location

Hôpital Saint Jean

Perpignan, 66046, France

Location

CHRU-Hopital du Haut -Leveque

Pessac, 33604, France

Location

CHU de Rennes Hopital de Pontchaillou

Rennes, 35033, France

Location

University Hospital OF Toulouse Purpan

Toulouse, 31059, France

Location

Hopital de Brabois Adultes

Vandœuvre-lès-Nancy, 54511, France

Location

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

Bologna, 40138, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50141, Italy

Location

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

Genova, 16132, Italy

Location

IEO istituto Europeo di Oncologia

Miano, 201401, Italy

Location

Universita Federico II di Napoli Nuovo Policlinico

Napoli, 80131, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Irccs/Crob

Rionero in Vulture (PZ), 85208, Italy

Location

Policlinico Tor Vergata (Universta Tor Vergata)

Roma, 00133, Italy

Location

Azienda Ospedaliera di Perugai Ospedale S. Maria della Miseri

Terni, 6156, Italy

Location

Hospital Universitari Vll D' Hebron

Barcelona, 8035, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Costa Del Sol

Marbella, 29600, Spain

Location

CH de Orense

Ourense, 32005, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, 31008, Spain

Location

Hosptial Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Onkologiska kliniken

Umeå, 90185, Sweden

Location

Akademiska Sjukhuset

Uppsala, 75185, Sweden

Location

Royal Bournemouth Hospital Haematology

Bournemouth, BH7 7DW, United Kingdom

Location

Royal Devon and Exeter Hospital Haematology Department

Exeter, EX2 5DW, United Kingdom

Location

St. James Institute of Oncology

Leeds, LS9 7TF, United Kingdom

Location

Royal Mardsen Hospital - Fulham (Satellite Site)

London, SW3 6U, United Kingdom

Location

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

Manchester, M20 4BX, United Kingdom

Location

Derrford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Southhampton University Hospital NHS Trust

Southhampton, SO16 6YD, United Kingdom

Location

Royal Mardsen NHS Foundation Trust

Sutton, SM2 SPT, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 28381416 RESULT

• 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.

  PMID: 21495023 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Recurrence

Interventions

Lenalidomide; Gemcitabine; Oxaliplatin; Rituximab; Etoposide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Coordination Complexes; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Limitations and Caveats

On 29 January 2013 the Stage 1 portion of the study was met and enrollment stopped. The Stage 1 results as assessed by the IRAC demonstrated that neither subtype met the prespecified requirement to be further studied in Stage 2.

Results Point of Contact

• Title: Anne McClain
• Organization: Celgene

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• Adrian Kilcoyne, MD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2010
• First Posted: September 9, 2010
• Study Start: September 2, 2010
• Primary Completion: July 4, 2013
• Study Completion: April 5, 2018
• Last Updated: November 25, 2019
• Results First Posted: August 20, 2014

Record last verified: 2019-11

Locations

ES (6); AU (3); CZ (2); GB (8); SE (2); IT (9); US (13); FR (11)