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
- Registration Number
- NCT00737529
- Lead Sponsor
- Celgene
- 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Follow up phase will continue until either 100% of the patients have died, are lost to follow up or have withdrawn consent or a maximum of 4 years from the last patient enrolled, whichever comes first.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for second primary malignancies and OS will continue until 100% of the patients have died, are lost to follow up, have withdrawn consent, or a maximum of 5 years from the last patient enrolled, whichever comes first.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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 134
- 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
-
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Lenalidomide 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieved an Overall Response According to the Independent Review Committee (IRC) 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.
Kaplan Meier Estimate of Duration of Response (DoR) 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 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.
- Secondary Outcome Measures
Name Time Method 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 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.
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 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.
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 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.
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 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
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 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.
Time to Response (TTR) 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.
Time to Complete Response (CR+CRu) According to the Independent Review Committee 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.
Overall Survival (OS) 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) 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.
Trial Locations
- Locations (70)
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Tower Cancer Research Foundation
🇺🇸Los Angeles, California, United States
Temple University School of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Alvin and Lois Lapidus Cancer Institute Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Hillman Cancer Institute at UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Boca Raton Community Hospital, Inc., Research Dept.
🇺🇸Boca Raton, Florida, United States
Landeskrankenhaus Salzburg
🇦🇹Salzburg, Austria
Institut Bergonie
🇫🇷Bordeaux, France
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Singapore General Hospital
🇸🇬Singapore, Singapore
Sheba Medical Center
🇮🇱Tel Hashomer, Israel
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
UCSD Moores Cancer Center
🇺🇸La Jolla, California, United States
Broward General Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Lake County Oncology and Hematology
🇺🇸The Villages, Florida, United States
Loyola University Medical Center - Smith
🇺🇸Maywood, Illinois, United States
University of Massachusetts Medical Center
🇺🇸Worcester, Massachusetts, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Washington University Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
NYU School of Medicine
🇺🇸New York, New York, United States
University of Rochester Cancer Center, James P. Wilmot Cancer Center
🇺🇸Rochester, New York, United States
Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
South Carolina Cancer Specialists
🇺🇸Hilton Head Island, South Carolina, United States
Universitair Ziekenhuis Leuven, Campus Gasthuisberg
🇧🇪Leuven, Belgium
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
University of Tennessee Cancer Institute
🇺🇸Memphis, Tennessee, United States
University of Virginia Cancer Center Clinical Trials Office
🇺🇸Charlottesville, Virginia, United States
Universitaetsklinik Innsbruck
🇦🇹Innsbruck, Austria
AZ Sint-Jan AV Brugge
🇧🇪Brugge, Belgium
Medical University of Vienna
🇦🇹Vienna, Austria
Oncologos del occidente S.A.
🇨🇴Pereira, Colombia
Hospital Universitario San Ignacio
🇨🇴Bogota, Colombia
UZ Gent
🇧🇪Gent, Belgium
Hopital Sud, CHU d'Amiens
🇫🇷Amiens, France
Hopital Emile Muller
🇫🇷Mulhouse, France
Hopital Henri Mondor
🇫🇷Créteil, France
Institut Curie
🇫🇷Paris, France
Hopital Robert Debre
🇫🇷Reims Cedex, France
Institut de Cancerologie de la Loire
🇫🇷Saint Jean Priest En Jarez, France
Hopital Cochin
🇫🇷Paris, France
Hopital Hautepierre
🇫🇷Strasbourg, France
University Hospital Wuerzburg
🇩🇪Wuerzburg, Germany
Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
🇭🇺Debrecen, Hungary
Kaposi Mor Oktato Korhaz
🇭🇺Kaposvar, Hungary
Petz Aladar Megyei Oktato Korhaz,II. Belgyogyaszat
🇭🇺Gyor, Hungary
Rambam Medical Center
🇮🇱Haifa, Israel
Rabin Medical Center
🇮🇱Petch Tikva, Israel
Universita Federico II di Napoli Nuovo Policlinico
🇮🇹Napoli, Italy
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Ospedale Civile dello Spirito Santo
🇮🇹Pescara, Italy
Universita Cattololica del Sacro Cuore
🇮🇹Roma, Italy
Centro De Cancer, Hospital Espanol Auxilio De Puerto Rico
🇵🇷San Juan, Puerto Rico
Hospital Clinico Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario La Fe
🇪🇸Valencia, Spain
Duran i Reynals Institut Catala d'Oncologia
🇪🇸L'Hospitalet de Llobregat, Spain
Hospital General De Elche
🇪🇸Alicante, Spain
Istanbul Universitesi Istanbul
🇹🇷Istanbul, Turkey
Gazi Universitesi
🇹🇷Besevler Ankara, Turkey
Royal Cornwall Hospitals Trust
🇬🇧Truro, United Kingdom
Ankara Universitesi Tip Fakultesi
🇹🇷Sihhiye Ankara, Turkey
Pasco Hernando Oncology Associates, PA
🇺🇸Brooksville, Florida, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
University of Debrecen, DEOEC, Institute of Internal Medicine
🇭🇺Debrecen, Hungary
MD Anderson Cancer Center, Orlando Regional Healthcare
🇺🇸Orlando, Florida, United States
Indiana University Cancer Center
🇺🇸Indianapolis, Indiana, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Nebraska
🇺🇸Omaha, Nebraska, United States