A Study to Determine the Efficacy and Safety of Lenalidomide in Patients With Mantle Cell NHL Who Have Relapsed or Progressed After Treatment With Bortezomib or Are Refractory to Bortezomib. The "EMERGE" Trial

NCT00737529 | Completed Phase 2 Results DMC

• 1 other identifier: CC-5013-MCL-001
• Study Type: interventional
• Target: 134
• Locations: 14 countries
• Sites: 70

Brief Summary

To evaluate the safety and efficacy of Lenalidomide (Revlimid (R)) in subjects with mantle cell lymphoma who have relapsed, progressed or are refractory to bortezomib.

Conditions

Mantle Cell Lymphoma

Keywords

Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; CC-5013; Revlimid; Lenalidomide

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Achieved an Overall Response According to the Independent Review Committee (IRC)

  Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response, Complete Response unconfirmed or Partial Response. Participants who had discontinued before any response has been observed, or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999); CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass \>1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses.

  From Day 1 of study treatment to progession or early treatment discontinuation; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days.

• Kaplan Meier Estimate of Duration of Response (DoR) According to the Independent Review Committee

  Kaplan Meier estimate for the duration of response (DoR) was calculated from the date of the first occurrence of initial response for responders (demonstrating evidence of at least a PR) to the date of first documented disease progression (any new lesion or increase by ≥ 50% of previously involved sites from nadir) or death (without documented progression) for participants who responded; participants who had not progressed (or died) were censored at the last valid assessment.

  From Day 1 of study drug to progression or early treatment discontinuation; up to data cut-off date of 06 April 2016; Median duration of treatment was 94.5 days.

Secondary Outcomes (9)

• Percentage of Participants With a Complete Response (CR) /Complete Response Unconfirmed (CRu) According to the Independent Review Committee

  From Day 1 of study drug to progression or early treatment discontinuation; up to data cut-off date of 06 April 2016; Median duration of treatment was 94.5 days

• Kaplan Meier Estimate of Duration of Complete Response (DoCR) (CR+CRu) According to the Independent Review Committee

  From Day 1 of study drug to progression or early discontinuation; up to data cut-off date of 06 April 2016; median time in follow-up was 16.34 months

• Kaplan-Meier Estimate of Progression-Free Survival (PFS) According to the Independent Review Committee

  From Day 1 of study drug to first documented date of disease progression; up to data cut-off date of 06 April 2016; median time in follow-up was 16.34 months

• Kaplan Meier Estimate of Time to Progression (TTP) According to the Independent Review Committee

  From Day 1 of study drug to first documented time of progression; up to data cut-off date of 06 April 2016; median time in follow-up was 16.34 months

• Kaplan-Meier Estimate of Time to Treatment Failure (TTF) According to the Independent Review Committee

  From Day 1 of study drug to first documented time of treatment failure; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days

Study Arms (1)

Lenalidomide

EXPERIMENTAL

Single agent Lenalidomide Lenalidomide: 10mg or 25 mg oral capsules on days 1 to 21 of each 28 day cycle and dependent on renal function; Participants with normal renal function (defined as Creatinine Clearance(CrCl)) of ≥ 60 mL/min in this study) received 25 mg of lenalidomide daily, and those with moderate renal insufficiency (CrCl) ≥ 30 mL/min but \< 60 mL/min) were started at a 10-mg dose. Participants could continue to receive treatment until disease progression, development of unacceptable AEs, or voluntary withdrawal.

Drug: lenalidomide

Interventions

lenalidomide DRUG

25mg oral capsules continuous days 1-21 each of a 28 day cycle

Also known as: Revlimid

Lenalidomide

Eligibility Criteria

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

You may qualify if:

• Biopsy proven mantle cell lymphoma
• Patients must have documents relapsed, refractory or PD after treatment with bortezomib
• Must have measureable disease on cross sectional imaging by CT
• Eastern Cooperative Oncology Group (ECOG) performance score 0,1 or 2
• Willing to follow pregnancy precautions

You may not qualify if:

• Any of the following laboratory abnormalities
• Absolute neutrophil count (ANC) \< 1,500 cells/mm3 (1.5 x 109/L)
• Platelet count \< 60,000/mm3 (60 x 109/L)
• Serum aspartate transaminase/Serum glutamic oxaloacetic transaminase(AST/SGOT) or alanine transaminase/Serum glutamic pyruvic transaminase (ALT/SGPT) \> 3.0 x upper limit of normal (ULN), except in patients with documented liver involvement by lymphoma.
• Serum total bilirubin \> 1.5 x ULN, except in cases of Gilbert's Syndrome and documented liver involvement by lymphoma.
• Calculated creatinine clearance (Cockcroft-Gault formula) of \< 30 mL /min
• Patients who are candidates for high dose chemotherapy/allogeneic stem cell transplant are not eligible
• History of active central nervous system (CNS) lymphoma within the previous 3 months
• Subjects not willing or unable to take deep vein thrombosis (DVT) prophylaxis
• Prior history of malignancies, other than MCL, unless the patient has been free of the disease for ≥ 3 years
• Positive Human immunodeficiency virus (HIV) or active Hepatitis B or C

Sponsors & Collaborators

• Celgene: lead

Study Sites (70)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Tower Cancer Research Foundation

Los Angeles, California, 90211, United States

Location

Boca Raton Community Hospital, Inc., Research Dept.

Boca Raton, Florida, 33486, United States

Location

Pasco Hernando Oncology Associates, PA

Brooksville, Florida, 34613, United States

Location

Broward General Medical Center

Fort Lauderdale, Florida, 33316, United States

Location

MD Anderson Cancer Center, Orlando Regional Healthcare

Orlando, Florida, 32806, United States

Location

Lake County Oncology and Hematology

The Villages, Florida, 32159, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Loyola University Medical Center - Smith

Maywood, Illinois, 60153, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Alvin and Lois Lapidus Cancer Institute Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Massachusetts Medical Center

Worcester, Massachusetts, 01655, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201-2014, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

University of Nebraska

Omaha, Nebraska, 68198-7680, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

NYU School of Medicine

New York, New York, 10016, United States

Location

University of Rochester Cancer Center, James P. Wilmot Cancer Center

Rochester, New York, 14642, United States

Location

Presbyterian Hospital

Charlotte, North Carolina, 28204, United States

Location

Temple University School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

Hillman Cancer Institute at UPMC

Pittsburgh, Pennsylvania, 15232, United States

Location

South Carolina Cancer Specialists

Hilton Head Island, South Carolina, 29926, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

University of Tennessee Cancer Institute

Memphis, Tennessee, 38104, United States

Location

University of Virginia Cancer Center Clinical Trials Office

Charlottesville, Virginia, 22908, United States

Location

Universitaetsklinik Innsbruck

Innsbruck, 6020, Austria

Location

Landeskrankenhaus Salzburg

Salzburg, 5020, Austria

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

AZ Sint-Jan AV Brugge

Bruges, 8000, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Universitair Ziekenhuis Leuven, Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Hospital Universitario San Ignacio

Bogotá, Colombia

Location

Oncologos del occidente S.A.

Pereira, Colombia

Location

Hopital Sud, CHU d'Amiens

Amiens, 80054, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Hopital Emile Muller

Mulhouse, 68070, France

Location

Hopital Cochin

Paris, 75014, France

Location

Institut Curie

Paris, 75248, France

Location

Hopital Robert Debre

Reims, 51092, France

Location

Institut de Cancerologie de la Loire

Saint Jean Priest En Jarez, 42277, France

Location

Hopital Hautepierre

Strasbourg, 67098, France

Location

University Hospital Wuerzburg

Würzburg, 97080, Germany

Location

Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum

Debrecen, 4032, Hungary

Location

University of Debrecen, DEOEC, Institute of Internal Medicine

Debrecen, 4032, Hungary

Location

Petz Aladar Megyei Oktato Korhaz,II. Belgyogyaszat

Győr, 9024, Hungary

Location

Kaposi Mor Oktato Korhaz

Kaposvár, 7400, Hungary

Location

Rambam Medical Center

Haifa, 35254, Israel

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

Rabin Medical Center

Petch Tikva, 49100, Israel

Location

Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Universita Federico II di Napoli Nuovo Policlinico

Napoli, 80131, Italy

Location

Ospedale Civile dello Spirito Santo

Pescara, 65124, Italy

Location

Universita Cattololica del Sacro Cuore

Roma, 00168, Italy

Location

Centro De Cancer, Hospital Espanol Auxilio De Puerto Rico

San Juan, 00919, Puerto Rico

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Hospital General De Elche

Alicante, 03203, Spain

Location

Duran i Reynals Institut Catala d'Oncologia

L'Hospitalet de Llobregat, 08907, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37003, Spain

Location

Hospital Universitario La Fe

Valencia, 46009, Spain

Location

Gazi Universitesi

Besevler Ankara, 06500, Turkey (Türkiye)

Location

Istanbul Universitesi Istanbul

Istanbul, 34390, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi

Sihhiye Ankara, 06100, Turkey (Türkiye)

Location

Royal Cornwall Hospitals Trust

Truro, TR1 3LJ, United Kingdom

Location

Related Publications (4)

• Goy A, Sinha R, Williams ME, Kalayoglu Besisik S, Drach J, Ramchandren R, Zhang L, Cicero S, Fu T, Witzig TE. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. J Clin Oncol. 2013 Oct 10;31(29):3688-95. doi: 10.1200/JCO.2013.49.2835. Epub 2013 Sep 3.

  PMID: 24002500 BACKGROUND

• Goy A, Kalayoglu Besisik S, Drach J, Ramchandren R, Robertson MJ, Avivi I, Rowe JM, Herbrecht R, Van Hoof A, Zhang L, Cicero S, Fu T, Witzig T. Longer-term follow-up and outcome by tumour cell proliferation rate (Ki-67) in patients with relapsed/refractory mantle cell lymphoma treated with lenalidomide on MCL-001(EMERGE) pivotal trial. Br J Haematol. 2015 Aug;170(4):496-503. doi: 10.1111/bjh.13456. Epub 2015 Apr 28.

  PMID: 25921098 RESULT

• Witzig TE, Luigi Zinzani P, Habermann TM, Tuscano JM, Drach J, Ramchandren R, Kalayoglu Besisik S, Takeshita K, Casadebaig Bravo ML, Zhang L, Fu T, Goy A. Long-term analysis of phase II studies of single-agent lenalidomide in relapsed/refractory mantle cell lymphoma. Am J Hematol. 2017 Oct;92(10):E575-E583. doi: 10.1002/ajh.24854. Epub 2017 Aug 28.

  PMID: 28699256 RESULT

• San-Miguel JF, Richardson PG, Gunther A, Sezer O, Siegel D, Blade J, LeBlanc R, Sutherland H, Sopala M, Mishra KK, Mu S, Bourquelot PM, Victoria Mateos M, Anderson KC. Phase Ib study of panobinostat and bortezomib in relapsed or relapsed and refractory multiple myeloma. J Clin Oncol. 2013 Oct 10;31(29):3696-703. doi: 10.1200/JCO.2012.46.7068. Epub 2013 Sep 9.

  PMID: 24019544 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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

Results Point of Contact

• Title: Senior Manager, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialsdisclosure@celgene.com

1-888-260-1599

Study Officials

• Lei Zhang, 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2008
• First Posted: August 19, 2008
• Study Start: December 22, 2008
• Primary Completion: April 6, 2016
• Study Completion: November 8, 2017
• Last Updated: December 13, 2018
• Results First Posted: September 9, 2013

Record last verified: 2018-12

Locations

ES (4); HU (4); TU (3); BE (3); FR (9); IL (4); CO (2); AU (3); IT (3); PR (1); GB (1); US (31); SG (1); DE (1)