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 (EMERGE)

December 11, 2018 updated by: Celgene

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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Follow up phase will continue until either 100% of the patients have died, are lost to follow up or have withdrawn consent or a maximum of 4 years from the last patient enrolled, whichever comes first.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for second primary malignancies and OS will continue until 100% of the patients have died, are lost to follow up, have withdrawn consent, or a maximum of 5 years from the last patient enrolled, whichever comes first.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.

Study Type

Interventional

Enrollment (Actual)

134

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Universitaetsklinik Innsbruck
      • Salzburg, Austria, 5020
        • Landeskrankenhaus Salzburg
      • Vienna, Austria, 1090
        • Medical University of Vienna
  • Belgium
      • Brugge, Belgium, 8000
        • AZ Sint-Jan AV Brugge
      • Gent, Belgium, 9000
        • UZ Gent
      • Leuven, Belgium, 3000
        • Universitair Ziekenhuis Leuven, Campus Gasthuisberg
  • Colombia
      • Bogota, Colombia
        • Hospital Universitario San Ignacio
      • Pereira, Colombia
        • Oncólogos del Occidente S.A.
  • France
      • Amiens, France, 80054
        • Hopital Sud, CHU d'Amiens
      • Bordeaux, France, 33076
        • Institut Bergonié
      • Créteil, France, 94010
        • Hôpital Henri Mondor
      • Mulhouse, France, 68070
        • Hôpital Emile Muller
      • Paris, France, 75248
        • Institut Curie
      • Paris, France, 75014
        • Hôpital Cochin
      • Reims Cedex, France, 51092
        • Hôpital Robert Debré
      • Saint Jean Priest En Jarez, France, 42277
        • Institut de Cancerologie de La Loire
      • Strasbourg, France, 67098
        • Hôpital Hautepierre
  • Germany
      • Wuerzburg, Germany, 97080
        • University Hospital Wuerzburg
  • Hungary
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
      • Debrecen, Hungary, 4032
        • University of Debrecen, DEOEC, Institute of Internal Medicine
      • Gyor, Hungary, 9024
        • Petz Aladar Megyei Oktato Korhaz,II. Belgyogyaszat
      • Kaposvar, Hungary, 7400
        • Kaposi Mór Oktató Kórház
  • Israel
      • Haifa, Israel, 35254
        • Rambam Medical Center
      • Jerusalem, Israel, 91120
        • Hadassah Medical Center
      • Petch Tikva, Israel, 49100
        • Rabin Medical Center
      • Tel Hashomer, Israel, 52621
        • Sheba Medical Center
  • Italy
      • Napoli, Italy, 80131
        • Universita Federico II di Napoli Nuovo Policlinico
      • Pescara, Italy, 65124
        • Ospedale Civile dello Spirito Santo
      • Roma, Italy, 00168
        • Universita Cattololica del Sacro Cuore
  • Puerto Rico
      • San Juan, Puerto Rico, 00919
        • Centro De Cancer, Hospital Espanol Auxilio De Puerto Rico
  • Singapore
      • Singapore, Singapore, 169608
        • Singapore General Hospital
  • Spain
      • Alicante, Spain, 03203
        • Hospital General de Elche
      • L'Hospitalet de Llobregat, Spain, 08907
        • Duran i Reynals Institut Catala d'Oncologia
      • Salamanca, Spain, 37003
        • Hospital Clínico Universitario de Salamanca
      • Valencia, Spain, 46009
        • Hospital Universitario La Fe
  • Turkey
      • Besevler Ankara, Turkey, 06500
        • Gazi Universitesi
      • Istanbul, Turkey, 34390
        • Istanbul Universitesi Istanbul
      • Sihhiye Ankara, Turkey, 06100
        • Ankara Universitesi Tip Fakultesi
  • United Kingdom
      • Truro, United Kingdom, TR1 3LJ
        • Royal Cornwall Hospitals Trust
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • La Jolla, California, United States, 92093
        • UCSD Moores Cancer Center
      • Loma Linda, California, United States, 92354
        • Loma Linda University Medical Center
      • Los Angeles, California, United States, 90211
        • Tower Cancer Research Foundation
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Boca Raton Community Hospital, Inc., Research Dept.
      • Brooksville, Florida, United States, 34613
        • Pasco Hernando Oncology Associates, PA
      • Fort Lauderdale, Florida, United States, 33316
        • Broward General Medical Center
      • Orlando, Florida, United States, 32806
        • MD Anderson Cancer Center, Orlando Regional Healthcare
      • The Villages, Florida, United States, 32159
        • Lake County Oncology and Hematology
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute of Emory University
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center - Smith
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Cancer Center
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Alvin and Lois Lapidus Cancer Institute Sinai Hospital of Baltimore
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48201-2014
        • Karmanos Cancer Institute
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University Siteman Cancer Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198-7680
        • University of Nebraska
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • New York, New York, United States, 10016
        • NYU School of Medicine
      • Rochester, New York, United States, 14642
        • University of Rochester Cancer Center, James P. Wilmot Cancer Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Presbyterian Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University School of Medicine
      • Pittsburgh, Pennsylvania, United States, 15232
        • Hillman Cancer Institute at UPMC
    • South Carolina
      • Hilton Head Island, South Carolina, United States, 29926
        • South Carolina Cancer Specialists
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • University of Tennessee Cancer Institute
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center Clinical Trials Office

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lenalidomide

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
25mg oral capsules continuous days 1-21 each of a 28 day cycle
Other Names:
  • Revlimid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Achieved an Overall Response According to the Independent Review Committee (IRC)
Time Frame: 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.
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
Time Frame: 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 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With a Complete Response (CR) /Complete Response Unconfirmed (CRu) According to the Independent Review Committee
Time Frame: 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
The percentage of participants whose best response was CR or CRu. Participants who had discontinued before CR/CRu was observed, or changed to other anti-lymphoma treatments before a CR/CRu response had been observed, were considered as non-responders. 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.
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
Time Frame: 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 estimates for the duration of CR/CRu was calculated from the date of the first occurrence of CR/CRu to the date of documented disease progression or death (without documented progression) for participants who obtained a CR/CRu; participants who had not progressed (or died) were censored at the last valid assessment.
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
Time Frame: 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 estimates of PFS was defined as the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever comes first. If a participant had not progressed or died, PFS was censored at the time of last adequate assessment when the participant was known not to have progressed. For participants who received other anti-lymphoma therapy with no evidence of progression, PFS was censored at time of last adequate tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment.
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
Time Frame: 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 progression was calculated as time from the start of the study drug therapy to the first observation of disease progression. Participants who died without progression were censored at the date of death; otherwise, the censoring rules presented above for PFS applied to the analysis of TTP. Progressive Disease(PD): Appearance of new lesion or increase by ≥50% from previously involved sites from nadir
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
Time Frame: 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
Time to treatment failure (TTF) was calculated from the start of study drug therapy to early discontinuation from treatment due to any cause, including disease progression, toxicity, or death and was based on site-reported data.
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
Time to Response (TTR)
Time Frame: 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
Time to Response was defined as the time from first dose of study drug to the date of the first response (having at least a PR) and was calculated only for responding participants.
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
Time to Complete Response (CR+CRu) According to the Independent Review Committee
Time Frame: 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
Time to Complete Response (CR+CRu) was defined as the time from the first dose of study drug to the date of the first occurrence of at least CRu and was calculated only for participants with CR or CRu.
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
Overall Survival (OS)
Time Frame: 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
Kaplan Meier estimate of overall survival was calculated from the time the first dose of study drug to death from any cause. Participants who had not died were censored at the last date the participant was known to be alive.
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
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time Frame: 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)
Adverse events were assessed using National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3: according to the following scale: Grade 1 = Mild Adverse Event (AE), Grade 2 = Moderate AE, Grade 3 = Severe and Undesirable AE, Grade 4 = Life-threatening or Disabling AE, and Grade 5 = Death; Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. after the first dose of study drug and within 28 days after the last dose. A TEAE is defined as any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celgene

Investigators

  • Study Director: Lei Zhang, MD, Celgene Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 22, 2008

Primary Completion (Actual)

April 6, 2016

Study Completion (Actual)

November 8, 2017

Study Registration Dates

First Submitted

August 15, 2008

First Submitted That Met QC Criteria

August 18, 2008

First Posted (Estimate)

August 19, 2008

Study Record Updates

Last Update Posted (Actual)

December 13, 2018

Last Update Submitted That Met QC Criteria

December 11, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CC-5013-MCL-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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