Clinical trial NCT00737529: 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
Official title: A Phase 2, Multicenter, Single-Arm, Open-Label Study To Determine The Efficacy And Safety Of Single-Agent Lenalidomide (Revlimid®) In Patients With Mantel Cell NHL Who Have Relapsed Or Progressed After Treatment With Bortezomib Or Are Refractory To Bortezomib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Keywords: Mantle Cell Lymphoma
Non-Hodgkin's Lymphoma
CC-5013
Revlimid
Lenalidomide
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2008-08-19
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Follow up phase will continue until either 100% of the patients have died, are lost to follow up or have withdrawn consent or a maximum of 4 years from the last patient enrolled, whichever comes first. All other efficacy and safety endpoints will be updated at this time. In the unlikely event that the study will be closed and patients are still responding to treatment at this time, Celgene will discuss with the treating physicians options to provide further treatment to the patient after study closure in line with local regulation.

Follow up for second primary malignancies and OS will continue until 100% of the patients have died, are lost to follow up, have withdrawn consent, or a maximum of 5 years from the last patient enrolled, whichever comes first.

10 October 2017: In regard to the last subject last visit date/study completion date, the prolongation of timelines is due to the bridging of a treatment gap for a patient responding to study medication until non-study medication is available.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Participants Who Achieved an Overall Response According to the Independent Review Committee (IRC)
timeFrame: 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.
measure: Kaplan Meier Estimate of Duration of Response (DoR) According to the Independent Review Committee
timeFrame: 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:
measure: Percentage of Participants With a Complete Response (CR) /Complete Response Unconfirmed (CRu) According to the Independent Review Committee
timeFrame: 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
measure: Kaplan Meier Estimate of Duration of Complete Response (DoCR) (CR+CRu) According to the Independent Review Committee
timeFrame: 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
measure: Kaplan-Meier Estimate of Progression-Free Survival (PFS) According to the Independent Review Committee
timeFrame: 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
measure: Kaplan Meier Estimate of Time to Progression (TTP) According to the Independent Review Committee
timeFrame: 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
measure: Kaplan-Meier Estimate of Time to Treatment Failure (TTF) According to the Independent Review Committee
timeFrame: 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
measure: Time to Response (TTR)
timeFrame: From Day 1 of study drug to time of first documented PR or better; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days
measure: Time to Complete Response (CR+CRu) According to the Independent Review Committee
timeFrame: From Day 1 of study drug to first documented CR/CRu or better; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days
measure: Overall Survival (OS)
timeFrame: From Day 1 of study drug to first documented date of progressive disease or death; up to the final data cut-off date of 30 March 2017; median duration of follow-up for surviving participants was 62.94 months
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From the first dose of lenalidomide through 28 days after the last dose during the follow-up phase; median (minimum, maximum) duration of treatment was 94.0 (1.0, 1950 days)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Boca Raton
country: United States
facility: Boca Raton Community Hospital, Inc., Research Dept.
state: Florida
city: Brooksville
country: United States
facility: Pasco Hernando Oncology Associates, PA
state: Florida
city: Fort Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Orlando
country: United States
facility: MD Anderson Cancer Center, Orlando Regional Healthcare
state: Florida
city: The Villages
country: United States
facility: Lake County Oncology and Hematology
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center - Smith
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Baltimore
country: United States
facility: Alvin and Lois Lapidus Cancer Institute Sinai Hospital of Baltimore
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University Siteman Cancer Center
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester Cancer Center, James P. Wilmot Cancer Center
state: New York
city: Charlotte
country: United States
facility: Presbyterian Hospital
state: North Carolina
city: Philadelphia
country: United States
facility: Temple University School of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hillman Cancer Institute at UPMC
state: Pennsylvania
city: Hilton Head Island
country: United States
facility: South Carolina Cancer Specialists
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Memphis
country: United States
facility: University of Tennessee Cancer Institute
state: Tennessee
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center Clinical Trials Office
state: Virginia
city: Innsbruck
country: Austria
facility: Universitaetsklinik Innsbruck
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Brugge
country: Belgium
facility: AZ Sint-Jan AV Brugge
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven, Campus Gasthuisberg
city: Bogota
country: Colombia
facility: Hospital Universitario San Ignacio
city: Pereira
country: Colombia
facility: Oncologos del occidente S.A.
city: Amiens
country: France
facility: Hopital Sud, CHU d'Amiens
city: Bordeaux
country: France
facility: Institut Bergonie
city: Créteil
country: France
facility: Hopital Henri Mondor
city: Mulhouse
country: France
facility: Hopital Emile Muller
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Institut Curie
city: Reims Cedex
country: France
facility: Hopital Robert Debre
city: Saint Jean Priest En Jarez
country: France
facility: Institut de Cancerologie de la Loire
city: Strasbourg
country: France
facility: Hopital Hautepierre
city: Wuerzburg
country: Germany
facility: University Hospital Wuerzburg
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
city: Debrecen
country: Hungary
facility: University of Debrecen, DEOEC, Institute of Internal Medicine
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz,II. Belgyogyaszat
city: Kaposvar
country: Hungary
facility: Kaposi Mor Oktato Korhaz
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petch Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
city: Napoli
country: Italy
facility: Universita Federico II di Napoli Nuovo Policlinico
city: Pescara
country: Italy
facility: Ospedale Civile dello Spirito Santo
city: Roma
country: Italy
facility: Universita Cattololica del Sacro Cuore
city: San Juan
country: Puerto Rico
facility: Centro De Cancer, Hospital Espanol Auxilio De Puerto Rico
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Alicante
country: Spain
facility: Hospital General De Elche
city: L'Hospitalet de Llobregat
country: Spain
facility: Duran i Reynals Institut Catala d'Oncologia
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Besevler Ankara
country: Turkey
facility: Gazi Universitesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul
city: Sihhiye Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospitals Trust
Study officials:
affiliation: Celgene Corporation
name: Lei Zhang, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.