A Study to Determine the Efficacy of Lenalidomide Versus Investigator's Choice in Patients With Relapsed or Refractory Mantle Cell Lymphoma (MCL)

NCT00875667 | Completed Phase 2 Results DMC

• 1 other identifier: CC-5013-MCL-002
• Study Type: interventional
• Target: 254
• Locations: 14 countries
• Sites: 97

Brief Summary

To evaluate the safety and efficacy of lenalidomide versus investigator choice in patients with relapsed or refractory mantle cell lymphoma.

Conditions

Mantle Cell Lymphoma; Lymphoma, Mantle-Cell

Keywords

Mantle Cell Lymphoma; Relapsed Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma; Lymphoma; MCL

Outcome Measures

Primary Outcomes (2)

• Kaplan Meier Estimate for Progression Free Survival (PFS) by Independent Review Committee (IRC) Central Review

  PFS was defined as time of randomization to the first observation of disease progression or death due to any cause, whichever was first. If a participant had not progressed or died, PFS was censored at the time of last 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 tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment.

  From randomization to progression of disease or death; up to data cut off date of 07 March 2014; overall median follow-up time was 93.9 weeks

• Kaplan Meier Estimate for Progression Free Survival by Investigator's Assessment at the Final Analysis

  Kaplan Meier estimates of PFS were defined as the time from randomization to the first observation of disease progression or death due to any cause, whichever was first. If a participant had not progressed or died, PFS was censored at the time of last completed 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 tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment.

  From randomization to progression of disease or death; up to study discontinuation of 09 October 2018; overall median follow-up time was 285 weeks

Secondary Outcomes (45)

• Percentage of Participants Who Achieved an Overall Response According to the IRC Central Review

  From date of randomization to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

• Percentage of Participants Who Achieved an Overall Response as Assessed by the Investigator at the Final Analysis

  From date of randomization to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm

• Kaplan Meier Estimate for Duration of Response (DOR) According to the IRC Central Review

  From date of randomization to the data cut-off date of 07 March 2014; median study duration was 70.7 weeks for the lenalidomide arm and 69.3 weeks for the investigators choice arm

• Kaplan Meier Estimate for Duration of Response as Assessed by the Investigator at the Final Analysis

  From date of randomization to the study discontinuation date of 09 October 2018; median study duration was 103.9 weeks for lenalidomide and 87.0 weeks for the investigator choice arm

• Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease According to the IRC Central Review

  From date of randomization to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Study Arms (2)

Lenalidomide

EXPERIMENTAL

Lenalidomide

Drug: Lenalidomide

Investigators choice single agent

ACTIVE COMPARATOR

Investigators choice single agent - Chlorambucil, Rituximab, Cytarabine, Gemcitabine, Fludarabine

Drug: Investigators choice single agent

Interventions

Lenalidomide DRUG

For patients with a creatinine clearance of ≥ 60 mL/min: 25 mg daily x 21 days of a 28 day cycle until disease progression or unacceptable toxicity. For patients who have a moderate renal insufficiency (creatinine clearance is ≥ 30 mL/min but \< 60mL/min: 10 mg daily x 21 days of a 28 day cycle (Cycles 1 and 2). After Cycle 2, if the patient remains free of Grade 3 or Grade 4 toxicity, the dose will be increased to 15 mg daily x 21 days of a 28 day cycle until disease progression or unacceptable toxicity.

Also known as: Revlimid, Rev, CC-5013

Lenalidomide

Investigators choice single agent DRUG

Investigators choice single agent - Chlorambucil, Rituximab, Cytarabine, Gemcitabine, or Fludarabine

Also known as: Leukeran, Ritux, Rituxan, cytosine arabinoside, Ara-C, Cytosar-U, Gemzar, fludarabine phosphate, Fludara

Investigators choice single agent

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 who are refractory to their regimen or have relapsed once, twice or up to three times and who have documented progressive disease
• Eastern Cooperative Oncology Group (ECOG) performance score 0,1, or 2
• Willing to follow pregnancy precaution

You may not qualify if:

• Any of the following laboratory abnormalities
• Absolute neutrophil count (ANC) \< 1,500 cells/mm\^3 (1.5 x 10\^9/L)
• Platelet count \< 60,000/mm\^3 (60 x 10\^9/L)
• Serum aspartate transaminase/serum glutamic oxaloacetic transaminase(AST/SGOT) or alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) \>3.0 x upper limit or normal (ULN), except patients with documented liver involvement by lymphoma
• Serum total bilirubin \> 1.5 x ULN, except in case of Gilbert's Syndrome and documented liver involvement by lymphoma.
• Calculated creatinine clearance (Cockcroft-Gault formula) of \< 30 mL/min
• History of active central nervous system (CNS) lymphoma within the previous 3 months
• Subjects not willing to take deep venous thrombosis (DVT) prophylaxis
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are sero-positive because of hepatitis B virus vaccine are eligible

Sponsors & Collaborators

• Celgene: lead

Study Sites (97)

UZ Brussels

Brussels, 1090, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

Cliniques Universitaires UCL de Mont-Godine

Yvoir, 5530, Belgium

Location

Teaching Hospital BrnoHemato-oncology Dept

Brno, 625 00, Czechia

Location

University Hospital2.Dep. of Int.med. hematology

Hradec Králové, 500 05, Czechia

Location

Charles University General Hospital

Prague, 12808, Czechia

Location

Rigshospitalet Department of Haematology L4042

Copenhagen, 2100, Denmark

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Polyclinique Bordeaux Nord Aquitaine Service Onco-Hematologie

Bordeaux, 33300, France

Location

Hotel Dieu

Clermont-Ferrand, 63003, France

Location

CHU Hopital Michallon

Grenoble, 38043, France

Location

Centre Hospitalier Departemental Les Oudrairies

La Roche-sur-Yon, 85025, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

CHRU-Hopital Claude Huriez

Lille, 59037, France

Location

CHU Dupuytren

Limoges, 87042, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Institut Paoli-Calmettes

Marseille, 13273, France

Location

CHU Montpellier - Hôpital Saint Eloi

Montpellier, 34295, France

Location

CHRU - Hotel Dieu

Nantes, 44093, France

Location

Centre Antoine Lacassagne Oncologie medicale et Hematologie

Nice, 06050, France

Location

Hopital Saint-Louis

Paris, 75010, France

Location

CHRU - Hopital du Haut Leveque

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU Rennes Hematology

Rennes, 35033, France

Location

Centre Henri Becquerel

Rouen, 79038, France

Location

Hopital civil

Strasbourg, 67091, France

Location

CHRU Hôpital de Hautepierre

Strasbourg, 67098, France

Location

CHRU Hopitaux de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Uniklinik Koln

Cologne, 50937, Germany

Location

Universitatsklinikum Essen

Essen, 45122, Germany

Location

Universitaetsklinikum FreiburgInnere Med.1, Haematologie

Freiburg im Breisgau, 79106, Germany

Location

UKG Universitatsklinikum Gottingen

Göttingen, 37099, Germany

Location

Asklepios Klinik St. Georg

Hamburg, D-20099, Germany

Location

Universitatsklinikum des Saarlandes

Homburg-Saar, 66421, Germany

Location

Stadtisches Klinikum Karlsruhe

Karlsruhe, 76135, Germany

Location

Universitatsklinik Munster

Münster, 48129, Germany

Location

University of Ulm

Ulm, 89081, Germany

Location

Attikon General University Hospital of Athens

Athens, 12462, Greece

Location

University of Patras

Pátrai, 26500, Greece

Location

Rambam Medical Center

Haifa, 35254, Israel

Location

Hadassah University Hospital

Jerusalem, 91120, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

A.O. Policlinico - Università di Bari

Bari, 70124, Italy

Location

A.O.U. di Bologna Policlinico S.Orsola-Malpighi

Bologna, 40138, Italy

Location

Ospedale Regionale di Bolzano

Bolzano, 39100, Italy

Location

Ospedale Ferrarotto

Catania, 95124, Italy

Location

Azienda Ospedaliera Universitaria San Martino

Genova, 16132, Italy

Location

Ematologia ed Immunologia

Lecce, 73100, Italy

Location

Istituto Europeo di Oncologia - IEO

Milan, 20141, Italy

Location

San Raffaele Scientific Institute

Milan, 20932, Italy

Location

Az. Osp. Vincenzo Cervello

Palermo, 90146, Italy

Location

I.R.C.C.S. Policlinico San Matteo

Pavia, 27100, Italy

Location

Az. Osp di Perugia

Perugia, 06100, Italy

Location

Ospedale S. Chiara

Pisa, 56126, Italy

Location

Azienda Ospedaliera "Bianchi-Melacrino-Morelli"

Reggio Calabria, 89100, Italy

Location

Reference Cancer Center of Basilicata

Rionero in Vulture, 85028, Italy

Location

IRCCS Casa Sollievo della Sofferenza

San Giovanni Rotondo, 71013, Italy

Location

Meander Medisch Centrum

Amersfoort, 3818 ES, Netherlands

Location

Medisch Spectrum Twente

Enshede, 7513, Netherlands

Location

Isala Klinieken

Zwolle, 8011, Netherlands

Location

Malopolskie Centrum medyczne s.c.

Krakow, 30-510, Poland

Location

Uniwersytet Jagiellonski Collegium Medicum

Krakow, 31-501, Poland

Location

Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi

Lodz, 93-510, Poland

Location

Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie w Warszawie

Warsaw, 02-781, Poland

Location

Nowotworww Krwi i Transplantacji Szpiku

Wroclaw, 50-367, Poland

Location

Dolnoslaskie Centrum Transplantacji Komorkowych

Wroclaw, 53-439, Poland

Location

Republic Clinical Oncology Dispensary

Kazan', 420029, Russia

Location

Institution of Russian Academy of Medical Sciences Russian Oncological Research Centre n.a. N. N. Bl

Moscow, 115447, Russia

Location

Nizhegorodskiy Regional Clinical Hospital named after N.A. Semashko

Nizhny Novgorod, 603126, Russia

Location

Novosibirsk State Regional Clinical Hospital

Novosibirsk, 630087, Russia

Location

Medical Radiology Research Centre RAMS

Obninsk, 249036, Russia

Location

Perm Territorial Oncology Dispensary

Perm, 614066, Russia

Location

Scientific Research Institute of OncologySoft Tissue Department

Rostov-on-Don, 344937, Russia

Location

St. Petersburg Research Institute of Hematology and Blood Transfusion

Saint Petersburg, 191024, Russia

Location

St. Petersburg Pavlov State Medical University

Saint Petersburg, 196022, Russia

Location

Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov

Saint Petersburg, 197341, Russia

Location

Saratov Medical University Chair of Professional Pathology and Haematology

Saratov, 410 028, Russia

Location

Volgograd Regional Clinical Oncology Dispensary 1

Volgograd, 400138, Russia

Location

Sverdlovsk Regional Clinical Hospital 1

Yekaterinburg, 620102, Russia

Location

Hospital Universitario Vall D Hebron

Barcelona, 8035, Spain

Location

Hospital de La Princesa

Madrid, 28006, Spain

Location

Hospital La Paz

Madrid, 28046, Spain

Location

Hospital Costa del Sol

Marbella, 29603, Spain

Location

Clinica Universitaria de Navarra

Pamplona, 31008, Spain

Location

Lund University Hosptial

Lund, 22185, Sweden

Location

University Hospital Uppsala

Uppsala, 75185, Sweden

Location

Royal Bournemouth Hosp

Bournemouth, BH7 7DW, United Kingdom

Location

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Newcastle Hospital Foundation Trust

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

John Radcliffe Hospital

Oxford, OX3 7LJ, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

The Royal Wolverhampton Hospital NHS Trust

Wolverhampton, WV10 0QP, United Kingdom

Location

Related Publications (2)

• Trneny M, Lamy T, Walewski J, Belada D, Mayer J, Radford J, Jurczak W, Morschhauser F, Alexeeva J, Rule S, Afanasyev B, Kaplanov K, Thyss A, Kuzmin A, Voloshin S, Kuliczkowski K, Giza A, Milpied N, Stelitano C, Marks R, Trumper L, Biyukov T, Patturajan M, Bravo MC, Arcaini L; SPRINT trial investigators and in collaboration with the European Mantle Cell Lymphoma Network. Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial. Lancet Oncol. 2016 Mar;17(3):319-331. doi: 10.1016/S1470-2045(15)00559-8. Epub 2016 Feb 16.

  PMID: 26899778 BACKGROUND

• Hagner PR, Chiu H, Ortiz M, Apollonio B, Wang M, Couto S, Waldman MF, Flynt E, Ramsay AG, Trotter M, Gandhi AK, Chopra R, Thakurta A. Activity of lenalidomide in mantle cell lymphoma can be explained by NK cell-mediated cytotoxicity. Br J Haematol. 2017 Nov;179(3):399-409. doi: 10.1111/bjh.14866. Epub 2017 Aug 2.

  PMID: 28771673 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma

Interventions

Lenalidomide; Chlorambucil; Rituximab; Cytarabine; Gemcitabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; 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; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine

Results Point of Contact

• Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
• Organization: Celgene Corporationi

ClinicalTrialDisclosure@Celgene.com

8882601599

Study Officials

• Marek Trneny, MD/PhD/Prof

  Head, Ist Dept Medicine, Charles University Hospital; Director, Institute of Hematology and Blood Transfusion; Chair, Czech Lymphoma Study Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2009
• First Posted: April 3, 2009
• Study Start: April 30, 2009
• Primary Completion: June 28, 2018
• Study Completion: October 9, 2018
• Last Updated: September 16, 2019
• Results First Posted: September 16, 2019

Record last verified: 2019-08

Locations

GB (9); SE (2); GR (2); PL (6); IT (15); FR (20); RU (13); ES (5); IL (4); BE (4); DE (9); NL (3); CZ (3); DK (2)