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

Mantle Cell Lymphoma Clinical Trial

— EMERGE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00737529
• Other study ID #: CC-5013-MCL-001
• Status: Completed
• Phase: Phase 2
• Start date: December 22, 2008
• Est. completion date: November 8, 2017

Study information

• Verified date: December 2018
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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Follow up phase will continue until either 100% of the patients have died, are lost to follow up or have withdrawn consent or a maximum of 4 years from the last patient enrolled, whichever comes first.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for second primary malignancies and OS will continue until 100% of the patients have died, are lost to follow up, have withdrawn consent, or a maximum of 5 years from the last patient enrolled, whichever comes first.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

• Status: Completed
• Enrollment: 134
• Est. completion date: November 8, 2017
• Est. primary completion date: April 6, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

Drug:
• lenalidomide
25mg oral capsules continuous days 1-21 each of a 28 day cycle

Locations

Country	Name	City	State
Austria	Universitaetsklinik Innsbruck	Innsbruck
Austria	Landeskrankenhaus Salzburg	Salzburg
Austria	Medical University of Vienna	Vienna
Belgium	AZ Sint-Jan AV Brugge	Brugge
Belgium	UZ Gent	Gent
Belgium	Universitair Ziekenhuis Leuven, Campus Gasthuisberg	Leuven
Colombia	Hospital Universitario San Ignacio	Bogota
Colombia	Oncologos del occidente S.A.	Pereira
France	Hopital Sud, CHU d'Amiens	Amiens
France	Institut Bergonie	Bordeaux
France	Hopital Henri Mondor	Créteil
France	Hopital Emile Muller	Mulhouse
France	Hopital Cochin	Paris
France	Institut Curie	Paris
France	Hopital Robert Debre	Reims Cedex
France	Institut de Cancerologie de la Loire	Saint Jean Priest En Jarez
France	Hopital Hautepierre	Strasbourg
Germany	University Hospital Wuerzburg	Wuerzburg
Hungary	Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum	Debrecen
Hungary	University of Debrecen, DEOEC, Institute of Internal Medicine	Debrecen
Hungary	Petz Aladar Megyei Oktato Korhaz,II. Belgyogyaszat	Gyor
Hungary	Kaposi Mor Oktato Korhaz	Kaposvar
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Rabin Medical Center	Petch Tikva
Israel	Sheba Medical Center	Tel Hashomer
Italy	Universita Federico II di Napoli Nuovo Policlinico	Napoli
Italy	Ospedale Civile dello Spirito Santo	Pescara
Italy	Universita Cattololica del Sacro Cuore	Roma
Puerto Rico	Centro De Cancer, Hospital Espanol Auxilio De Puerto Rico	San Juan
Singapore	Singapore General Hospital	Singapore
Spain	Hospital General De Elche	Alicante
Spain	Duran i Reynals Institut Catala d'Oncologia	L'Hospitalet de Llobregat
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario La Fe	Valencia
Turkey	Gazi Universitesi	Besevler Ankara
Turkey	Istanbul Universitesi Istanbul	Istanbul
Turkey	Ankara Universitesi Tip Fakultesi	Sihhiye Ankara
United Kingdom	Royal Cornwall Hospitals Trust	Truro
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Alvin and Lois Lapidus Cancer Institute Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Boca Raton Community Hospital, Inc., Research Dept.	Boca Raton	Florida
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Pasco Hernando Oncology Associates, PA	Brooksville	Florida
United States	Presbyterian Hospital	Charlotte	North Carolina
United States	University of Virginia Cancer Center Clinical Trials Office	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	South Carolina Cancer Specialists	Hilton Head Island	South Carolina
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	UCSD Moores Cancer Center	La Jolla	California
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Tower Cancer Research Foundation	Los Angeles	California
United States	Loyola University Medical Center - Smith	Maywood	Illinois
United States	University of Tennessee Cancer Institute	Memphis	Tennessee
United States	NYU School of Medicine	New York	New York
United States	University of Nebraska	Omaha	Nebraska
United States	MD Anderson Cancer Center, Orlando Regional Healthcare	Orlando	Florida
United States	Temple University School of Medicine	Philadelphia	Pennsylvania
United States	Hillman Cancer Institute at UPMC	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Cancer Center, James P. Wilmot Cancer Center	Rochester	New York
United States	Washington University Siteman Cancer Center	Saint Louis	Missouri
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Lake County Oncology and Hematology	The Villages	Florida
United States	University of Massachusetts Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Colombia,  France,  Germany,  Hungary,  Israel,  Italy,  Puerto Rico,  Singapore,  Spain,  Turkey,  United Kingdom, 

References & Publications (3)

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/refractor — View 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. — View 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 ce — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	Percentage of Participants With a Complete Response (CR) /Complete Response Unconfirmed (CRu) According to the Independent Review Committee	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
Secondary	Kaplan Meier Estimate of Duration of Complete Response (DoCR) (CR+CRu) According to the Independent Review Committee	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
Secondary	Kaplan-Meier Estimate of Progression-Free Survival (PFS) According to the Independent Review Committee	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
Secondary	Kaplan Meier Estimate of Time to Progression (TTP) According to the Independent Review Committee	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
Secondary	Kaplan-Meier Estimate of Time to Treatment Failure (TTF) According to the Independent Review Committee	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
Secondary	Time to Response (TTR)	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
Secondary	Time to Complete Response (CR+CRu) According to the Independent Review Committee	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
Secondary	Overall Survival (OS)	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
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs)	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)