Study of VELCADE and Rituximab in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

NCT ID: NCT00312845

Last Updated: 2012-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 676 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2010-07-31

Brief Summary

The purpose of this study is to determine if the combination of VELCADE and rituximab improves progression free survival relative to rituximab alone in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (B-NHL) who never received rituximab or who have previously responded to rituximab. This is an international study being conducted in the United States and in many countries around the world. A complete list of study locations is listed below.

Conditions

Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bortezomib + Rituximab

Group Type: EXPERIMENTAL

Bortezomib + Rituximab

Intervention Type: DRUG

VELCADE for Injection will be administered weekly on Days 1,8,15, and 22 of a 35-day cycle in combination with 4 doses of rituximab once a week on Days 1,8,15, and 22 of Cycle 1 and in combination with a single dose of rituximab on Day 1 of Cycles 2 to 5.

Rituximab

Group Type: ACTIVE_COMPARATOR

Rituximab

Intervention Type: DRUG

rituximab once a week on Days 1,8,15, and 22 of Cycle 1, and as a single dose on Day 1 of Cycles 2 to 5 (for a total of 8 doses).

Interventions

Bortezomib + Rituximab

VELCADE for Injection will be administered weekly on Days 1,8,15, and 22 of a 35-day cycle in combination with 4 doses of rituximab once a week on Days 1,8,15, and 22 of Cycle 1 and in combination with a single dose of rituximab on Day 1 of Cycles 2 to 5.

Intervention Type: DRUG

Rituximab

rituximab once a week on Days 1,8,15, and 22 of Cycle 1, and as a single dose on Day 1 of Cycles 2 to 5 (for a total of 8 doses).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:

• Man or woman and age 18 years or older
• Diagnosis of follicular B-NHL of the following subtypes (World Health Organization [WHO] classification 1997): follicular lymphoma (FL) (Grades 1 and 2).
• Documented relapse or progression following prior antineoplastic treatment. New lesions or objective evidence of progression of existing lesions must document relapse or progression following the previous therapy.

If any prior regimen included rituximab, the subject must have responded (complete response [CR], unconfirmed complete response [CRu], partial response [PR]), and the time to progression (TTP) from the first dose of rituximab must have been 6 months or more.

• At least 1 measurable tumor mass (greater than 1.5 cm in the longest dimension and greater than 1.0 cm in the short axis) that has not been previously irradiated, or has grown since previous irradiation
• In the opinion of the investigator the decision to initiate treatment is justified to manage the subject's lymphoma
• No active central nervous system lymphoma
• Eastern Cooperative Oncology Group [ECOG] status ≤ 2
• Female subjects must be postmenopausal (for at least 6 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening.
• Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• In countries where health authorities have approved the pharmacogenomic testing, subjects or their legally acceptable representatives must have signed a separate informed consent that they agree to participate in the genetic part and protein testing part of the study; participation in the genetic and protein testing component is mandatory for pharmacogenomics testing, but optional for serum protein testing and future testing.

Exclusion Criteria

Potential subjects who meet any of the following criteria will be excluded from participating in the study:

• Diagnosed or treated for a malignancy other than NHL within 1 year of randomization, or who were previously diagnosed with a malignancy other than NHL and have any radiographic or biochemical marker evidence of malignancy. Subjects with completely resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy are not excluded.
• Clinical evidence of a transformation from indolent NHL to a more aggressive form of NHL.
• History of disallowed therapies:

• Prior treatment with VELCADE
• Antineoplastic (including unconjugated therapeutic antibodies), experimental, or radiation therapy within 3 weeks before randomization
• Nitrosoureas within 6 weeks before randomization
• Radioimmunoconjugates or toxin immunoconjugates within 10 weeks before randomization
• Stem cell transplant within 6 months before randomization
• Major surgery within 2 weeks before randomization
• Residual toxic effects of previous therapy or surgery of Grade 3 or worse
• Peripheral neuropathy or neuropathic pain of Grade 2 or worse
• Have received an experimental drug or used an experimental medical device within 21 days before the planned start of treatment.
• History of allergic reaction attributable to compounds containing boron or mannitol
• Known anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab including polysorbate 80 and sodium citrate dihydrate
• Concurrent treatment with another investigational agent
• Female subject who is pregnant or breast-feeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role: collaborator

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

East Alabama Medical Center

Opelika, Alabama, United States

Central Hematology Oncology Medical Group, Inc

Alhambra, California, United States

Comprehensive Blood and Cancer Center

Bakersfield, California, United States

Providence Saint Joseph Medical Center

Burbank, California, United States

St. Jude Heritage Medical Group

Fullerton, California, United States

Wilshire Oncology Medical Group, Inc.

La Verne, California, United States

Pacific Shores Medical Group

Long Beach, California, United States

University of Southern California

Los Angeles, California, United States

University of California, Los Angeles

Los Angeles, California, United States

North Valley Hematology Oncology

Mission Hills, California, United States

University of California, Irvine Medical Center

Orange, California, United States

Ventura County Hematology-Oncology Specialists

Oxnard, California, United States

Cancer Care Associates Medical Group, Inc.

Redondo Beach, California, United States

Central Coast Medical Oncology Corporation

Santa Maria, California, United States

Norwalk Medical Group

Norwalk, Connecticut, United States

Hematology Oncology PC

Stamford, Connecticut, United States

Integrated Community Oncology Network

Jacksonville, Florida, United States

Innovative Clinical Research of South Florida

Miami, Florida, United States

Palm Beach Cancer Institute

West Palm Beach, Florida, United States

Emory Univeersity ,Winship Cancer Institute

Atlanta, Georgia, United States

Suburban Hematology-Oncology Associates

Lawrenceville, Georgia, United States

Northwest Georgia Oncology Centers, P.C.

Marietta, Georgia, United States

North Idaho Cancer Center

Coeur d'Alene, Idaho, United States

Investigative Clinical Research of Indiana

Indianapolis, Indiana, United States

Siouxland Hematolgoy-Oncology Associates

Sioux City, Iowa, United States

Kansas City Cancer Center, LLC

Kansas City, Kansas, United States

Louisville Oncology

Louisville, Kentucky, United States

Hematology & Oncology Specialists

Metairie, Louisiana, United States

Sinai Hospital

Baltimore, Maryland, United States

Hattiesburg Clinic

Hattesburg, Missouri, United States

Southeastern Medical Oncology Center

Goldsboro, North Carolina, United States

Oregon Health & Science University

Portland, Oregon, United States

Lancaster Cancer Center, Ltd.

Lancaster, Pennsylvania, United States

The Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

South Carolina Oncology Associates, PA

Columbia, South Carolina, United States

South Carolina Oncology Associates

Columbia, South Carolina, United States

Vanderbilt University

Nashville, Tennessee, United States

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Oncology Consultants

Houston, Texas, United States

South Texas Oncology and Hematology

San Antonio, Texas, United States

Medical College of Wisconsin Milwaukee

Milwaukee, Wisconsin, United States

Higa San Martin

La Plata - Buenos Aires, , Argentina

Hospital Professor Rodolfo Rossi

La Plata - Buenos Aires, , Argentina

Centro Oncologico Integracion Regional

Mendoza, , Argentina

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Peter MacCallum Cancer Institute

East Melbourne, Victoria, Australia

Alfred Hospital

Melbourne, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Fremantle Hospital

Fremantle, Western Australia, Australia

ULB Erasme

Anderlecht, , Belgium

AZ Stuivenberg

Antwerp, , Belgium

AZ Sint Jan

Bruges, , Belgium

Institute J. Bordet

Brussels, , Belgium

Clinique Notre Dame

Charleroi, , Belgium

UZ Antwerpen - Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

UZ Gent - Universitair Ziekenhuis Gent

Ghent, , Belgium

Virga Jesse Ziekenhuis, Dienst Hematologie

Hasselt, , Belgium

CHR La Citadelle

Liège, , Belgium

CHU Sart Tilman

Liège, , Belgium

Heilig Hart Roeselare

Roeselare, , Belgium

Servico de Oncologia do Hospital Sao Lucas da PUC do rio Grande do Sul

Porto Alegre, Rio Grande do Sul, Brazil

Instituto Nacional de Cancer

Rio de Janeiro, , Brazil

Hospital Brigadeiro

São Paulo, , Brazil

Faculdade de Medicina do ABC

São Paulo, , Brazil

Toronto Sunnybrook Regional Cancer Centre

Toronto, Ontario, Canada

University Health Network - Princess Margaret Hospital

Toronto, Ontario, Canada

Juravinski Cancer Centre

Hamilton, , Canada

West China Hospital of Sichuan

Chengdu, Sichuan, China

Cancer Hospital (Institute), CAMS&PUMC

Beijing, , China

Beijing Cancer Hospital

Beijing, , China

Peking University People's Hospital

Beijing, , China

Affiliated Hospital of the Academy of Military Medical Sciences

Beijing, , China

Cancer Center, Sun Yat-Sen University

Guangzhou, , China

Peking University Third Hospital

Haidian District Beijing, , China

RuiJin Hospital

Shanghai, , China

Cancer Hospital - FuDan University

Shanghai, , China

Bank of Cyprus Oncology Centre

Nicosia, , Cyprus

Fakultni nemocnice Brno

Brno, , Czechia

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Vseobecna Fakultni Nemocnice

Prague, , Czechia

Paijat - Hameen Keskussairaala

Lahti, , Finland

Satakunnan Keskussairaala

Pori, , Finland

Institut Bergonie

Bordeaux, , France

Clinique Victor Hugo

Le Mans, , France

Hopital Claude Huriez

Lille, , France

Centre Léon Bérard

Lyon, , France

Hopital Hotel Dieu

Nantes, , France

Service des Maladies due sang - Hopital haut Leveque

Pessac, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Onkologische Schwerpunktpraxis

Herrsching am Ammersee, , Germany

Universitatsklinikum Munster - Klinik fur Innere Medizin

Münster, , Germany

Praxis für Hämetologie und Oncologie

Würzburg, , Germany

Laiko General Hospital of Athens - 1st Internist Clinic - Hematology Department

Athens, , Greece

University General Hospital Attikon - 2nd Department of Internal Medicine - Propedeutic & Research Institute

Athens, , Greece

University Hospital of Patras - Department of Internal Medicine - Hematology Division

Rio Patras, , Greece

Debreceni Egyetem, Orvos- es Egeszsegtudomanyl Centrum, iii. Belgyogyaszati Klinika

Debrecen, , Hungary

Petz Aladar County Hospital

Győr, , Hungary

SZEgedi Tudomanyegyetem, II Belgyaszati Klinika

Szeged, , Hungary

Institution Manipal Hospital

Bangalore, , India

Postgraduate Institute of Medical Education and Research

Chandigarh, , India

Apollo Speciality Hospital

Chennai, , India

Nizam's Institute of Medical Sciences

Hyderabaad, , India

SMS Medical College Hospital

Jaipur, , India

Apollo Hospitals, Hyderabad Apollo Hospital Complex

Jubilee Hills, , India

Shirdi Saibaba Cancer Hospital

Karnataka, , India

Department of Medical Oncology - Regional Cancer Centre

Kerala, , India

Regional Cancer Centre

Kerala, , India

Tata Memorial Centre

Mumbai, , India

Soroka Medical Center

Beersheba, , Israel

Rambam Medical Center

Haifa, , Israel

Hadassah Medical Center

Jerusalem, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Sorraski Tel Aviv Medical Center

Tel Aviv, , Israel

Sheba Medical Center

Tel Litwinsky, , Israel

Azienda Ospedaliero Universitaria di Bologna

Bologna, , Italy

Universita degli Studi di Perugia

Perugia, , Italy

Azienda Ospedallera Universitaria Policlinico Tor Vergata

Roma, , Italy

Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista

Torino, , Italy

Instituto Nacional De Ciencias Medicas Y Nutricion Salvador Zubiran

Delagacion Tlalpan, , Mexico

Instituto Nacional De Cancerologia Incan

Delagacion Tlalpan, , Mexico

Hospital Universitario Dr. Jose Eleuterio Gonzalez UANL

Monterrey, Nuevo Leon, , Mexico

Canterbury Health Laboratories

Christchurch, , New Zealand

Klinika Hematologii Instytut Chorob Wewnetrznych

Gdansk, , Poland

Klinika Hematologii CMUJ

Krakow, , Poland

Klinika Hematologii - Uniwersytetu Medycznego

Lodz, , Poland

Klinika Hematologii i Transplantologii Szpiku AM

Lublin, , Poland

Wojskowy Instytut Medyczny - Klinika Hematologii

Warsaw, , Poland

Instytut Hematologii i Transfuzjologii

Warsaw, , Poland

Klinika Hematologii AM

Warsaw, , Poland

Klinika Nowotworow Ukladu Chlonnego

Warsaw, , Poland

Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku

Wroclaw, , Poland

Servico de Hematologia - Hospital de Dia - Hospital Da Universidade de Coimbra

Coimbra, , Portugal

Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E. - Departmento de Hematologia

Lisbon, , Portugal

Hospital de Dia de Hematologia - Hospital de Santa Maria E.P.E.

Lisbon, , Portugal

Serviço de Onco-hematologia, Instituto Português de Oncologia do Porto Franscisco Gentil, EPE

Porto, , Portugal

San Juan VA Medical Center

San Juan, , Puerto Rico

Spitalul clinic de urgenta

Brasov, , Romania

Institutul Clinic Fundeni Clinica de Hematologie

Bucharest, , Romania

Spitalul Universitar de Urgenta Hematologie

Bucharest, , Romania

Spitalul Clinic judetean de urgenta "Sf. Spiridon, Clinica Hematologie

Iași, , Romania

Spitalul Clinic judetean de urgenta Mures

Târgu Mureş, , Romania

Arkhangelsk Region Clinical Hospital

Arghangelsk, , Russia

Altay Regional Oncology Dispensary

Barnaul, , Russia

Belgorod Regional Oncology Center

Belgorod, , Russia

Cheliabinsk Regional Oncology Dispensary

Chelyabinsk, , Russia

1st Republican Clinical Hospital of Udmurtia

Izhevsk, , Russia

Cancer Research Center

Moscow, , Russia

S.P. Botkin Moscow City Clinical Hospital

Moscow, , Russia

Moscow Region Clinical Research Institute

Moscow, , Russia

Semashko Central Clinical Hospital #2

Moscow, , Russia

City Oncology Hospital #62

Moscow, , Russia

Nizhniy Novgorod Region Clinical Hospital

Nizhny Novgorod, , Russia

Novosibirsk State Regional Clinical Hospital

Novosibirsk, , Russia

Novosibirsk State Medical University

Novosibirsk, , Russia

Medical Scientifical Radiology Center

Obninsk, , Russia

Republikan Hospital named after V.A. Baranov

Petrozavodsk, , Russia

St. Petersburg Clinical Research Institute of Hematology and Transfusiology

Saint Petersburg, , Russia

Saint Petersburg Pavlov State Medical University

Saint Petersburg, , Russia

St. Petersburg City Hospital #31

Saint Petersburg, , Russia

Saratov State Medical University

Saratov, , Russia

Tomsk Research Oncology Institute

Tomsk, , Russia

Republican Clinical Hospital of Bashkorkostan

Ufa, , Russia

Ekaterinburg City Clinical Hospital #7

Yekaterinburg, , Russia

FN F.D. Roosevelt - Oddelenie hematologie

Banska Bysterica, , Slovakia

Fakultna nemocnica L. Pasteura - Klinika hematologie a onkohematologie

Košice, , Slovakia

Vychodoslovensky Onkologicky Ustave, a.s.

Košice, , Slovakia

Martinska FN, Klinika hematologie a transfuziologie

Martin, , Slovakia

GVI Oncology Clinical Trial Unit

Panorama, Cape Town, South Africa

Mary Potter Oncology Centre - Little Company of Mary Hospital

Groenkloof, Pretoria, , South Africa

Chris Hani Baragwanath Hospital

Johannesburg, , South Africa

East Cape Oncology Centre - St. Georges Hospital

Port Elizabeth, , South Africa

Lung Cancer Center - National Cancer Center

Gyeonggi-do, , South Korea

Samsung Medical Center - Division of Hematology-Oncology, Department of Medicine

Ilmon-Dong, Kangnam-Ku, Seoul, , South Korea

Hematology-Oncology Clinic, Center for Specific Organs Cancer - National Cancer Center

Ilsandong-Gu, Goyang-Si, and Gyeonggi-Do, , South Korea

Samsung Medical Center - Department of Internal Medicine

Ilwon Dong, Kangnam-Ku, Seoul, , South Korea

Severance Hospital, Yonsei University College of Medicine

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Hospital Durans I Reynals - Institut Catala d'Oncologia

Barcelona, , Spain

Hospital Germans Trias i Pujol Institut Catala d'Oncologia

Barcelona, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Onkologiska kliniken Universitetssjukhuset

Lund, , Sweden

Centrum for Hematologi Karolinska University Hospital

Stockholm, , Sweden

Hematologiska kliniken M54 Karolinska University Hospital

Stockholm, , Sweden

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Ramathibodi Hospital, Mahidol University

Bangkok, , Thailand

Siriraj Hospital, Mahidol University

Bangkok, , Thailand

Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University

Chiang Mai, , Thailand

Cherkassy Regional Oncology Dispensary

Cherkassy, , Ukraine

Dnepropetrovsk Regional Clinical Oncology Dispensary

Dnipro, , Ukraine

Institute for Emergency and Urgent Medical Assistance named after V.K. Gusak of AMS of Ukraine

Donetsk, , Ukraine

Khmelnitskiy Regional Hopsital

Khmelnitsky, , Ukraine

Kiev Center of Marrow Transplantaion

Kiev, , Ukraine

Krivoy Rog Oncology Dispensary

Kryvyi Rih, , Ukraine

Institute of Blood Pathology and Transfusional Medicine of AMS of Ukraine, Lviv Clinical Hospital #5

Lviv, , Ukraine

Ukrainian Medical Stomatological Academy, Poltava Regional Dispensary

Poltava, , Ukraine

Crimean Republic Clinical Oncology Dispensary

Simferopol, , Ukraine

Zhitomir Gerbachevsky Regional Clinical Hospital

Zhytomyr, , Ukraine

Aberdeen Royal Infirmary - Department of Haematology

Aberdeen, , United Kingdom

Addenbrooke's Hospital - Department of Haematology

Cambridge, , United Kingdom

University Hospital of Wales

Cardiff, , United Kingdom

Guy's & St. Thomas Hospital

London, , United Kingdom

Derriford Hospital - Department of Haematology

Plymouth, , United Kingdom

Taunton & Somerset Hospital

Taunton, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; China; Cyprus; Czechia; Finland; France; Germany; Greece; Hungary; India; Israel; Italy; Mexico; New Zealand; Poland; Portugal; Puerto Rico; Romania; Russia; Slovakia; South Africa; South Korea; Spain; Sweden; Thailand; Ukraine; United Kingdom

References

Zinzani PL, Khuageva NK, Wang H, Garicochea B, Walewski J, Van Hoof A, Soubeyran P, Caballero D, Buckstein R, Esseltine DL, Theocharous P, Enny C, Zhu E, Elsayed YA, Coiffier B. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naive or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012 Oct 22;5:67. doi: 10.1186/1756-8722-5-67.

Reference Type: DERIVED

PMID: 23088650 (View on PubMed)

Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL; LYM-3001 study investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011 Aug;12(8):773-84. doi: 10.1016/S1470-2045(11)70150-4. Epub 2011 Jul 1.

Reference Type: DERIVED

PMID: 21724462 (View on PubMed)

Other Identifiers

26866138-LYM-3001

Identifier Type: -

Identifier Source: org_study_id