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

Non-Hodgkin's Lymphoma Clinical Trial

Official title:

A Randomized, Open-Label, Multicenter Study of VELCADE With Rituximab or Rituximab Alone in Subjects With Relapsed or Refractory, Rituximab Naive or Sensitive Follicular B-cell Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00312845
• Other study ID #: 26866138-LYM-3001
• Status: Completed
• Phase: Phase 3
• First received: April 7, 2006
• Last updated: June 19, 2012
• Start date: March 2006
• Est. completion date: July 2010

Study information

• Verified date: June 2012
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 676
• Est. completion date: July 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 (ß-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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• 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.
• 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).

Locations

Country	Name	City	State
Argentina	Higa San Martin	La Plata - Buenos Aires
Argentina	Hospital Professor Rodolfo Rossi	La Plata - Buenos Aires
Argentina	Centro Oncologico Integracion Regional	Mendoza
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Peter MacCallum Cancer Institute	East Melbourne	Victoria
Australia	Fremantle Hospital	Fremantle	Western Australia
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	ULB Erasme	Anderlecht
Belgium	AZ Stuivenberg	Antwerpen
Belgium	AZ Sint Jan	Brugge
Belgium	Institute J. Bordet	Bruxelles
Belgium	Clinique Notre Dame	Charleroi
Belgium	UZ Antwerpen - Universitair Ziekenhuis Antwerpen	Edegem
Belgium	UZ Gent - Universitair Ziekenhuis Gent	Gent
Belgium	Virga Jesse Ziekenhuis, Dienst Hematologie	Hasselt
Belgium	CHR La Citadelle	Liege
Belgium	CHU Sart Tilman	Liege
Belgium	Heilig Hart Roeselare	Roeselare
Brazil	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	Faculdade de Medicina do ABC	Sao Paulo
Brazil	Hospital Brigadeiro	Sao Paulo
Canada	Juravinski Cancer Centre	Hamilton
Canada	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario
Canada	University Health Network - Princess Margaret Hospital	Toronto	Ontario
China	Affiliated Hospital of the Academy of Military Medical Sciences	Beijing
China	Beijing Cancer Hospital	Beijing
China	Cancer Hospital (Institute), CAMS&PUMC	Beijing
China	Peking University People's Hospital	Beijing
China	West China Hospital of Sichuan	Chengdu	Sichuan
China	Cancer Center, Sun Yat-Sen University	Guangzhou
China	Peking University Third Hospital	Haidian District Beijing
China	Cancer Hospital - FuDan University	Shanghai
China	RuiJin Hospital	Shanghai
Cyprus	Bank of Cyprus Oncology Centre	Nikosia
Czech Republic	Fakultni nemocnice Brno	Brno
Czech Republic	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czech Republic	Fakultni nemocnice Olomouc	Olomouc
Czech Republic	Vseobecna Fakultni Nemocnice	Praha
Finland	Paijat - Hameen Keskussairaala	Lahti
Finland	Satakunnan Keskussairaala	Pori
France	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 Benite
Germany	Onkologische Schwerpunktpraxis	Herrsching
Germany	Universitatsklinikum Munster - Klinik fur Innere Medizin	Munster
Germany	Praxis für Hämetologie und Oncologie	Würzburg
Greece	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
Hungary	Debreceni Egyetem, Orvos- es Egeszsegtudomanyl Centrum, iii. Belgyogyaszati Klinika	Debrecen
Hungary	Petz Aladar County Hospital	Gyor
Hungary	SZEgedi Tudomanyegyetem, II Belgyaszati Klinika	Szeged
India	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
Israel	Soroka Medical Center	Beer Sheva
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 HaShomer
Italy	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
Korea, Republic of	Lung Cancer Center - National Cancer Center	Gyeonggi-Do
Korea, Republic of	Samsung Medical Center - Division of Hematology-Oncology, Department of Medicine	Ilmon-Dong, Kangnam-Ku, Seoul
Korea, Republic of	Hematology-Oncology Clinic, Center for Specific Organs Cancer - National Cancer Center	Ilsandong-Gu, Goyang-Si, and Gyeonggi-Do
Korea, Republic of	Samsung Medical Center - Department of Internal Medicine	Ilwon dong, Kangnam-Ku, Seoul
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University College of Medicine	Seoul
Mexico	Instituto Nacional De Cancerologia Incan	Delagacion Tlalpan
Mexico	Instituto Nacional De Ciencias Medicas Y Nutricion Salvador Zubiran	Delagacion Tlalpan
Mexico	Hospital Universitario Dr. Jose Eleuterio Gonzalez UANL	Monterrey, Nuevo leon
New Zealand	Canterbury Health Laboratories	Christchurch
Poland	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	Warsawa
Poland	Instytut Hematologii i Transfuzjologii	Warszawa
Poland	Klinika Hematologii AM	Warszawa
Poland	Klinika Nowotworow Ukladu Chlonnego	Warszawa
Poland	Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku	Wroclaw
Portugal	Servico de Hematologia - Hospital de Dia - Hospital Da Universidade de Coimbra	Coimbra
Portugal	Hospital de Dia de Hematologia - Hospital de Santa Maria E.P.E.	Lisboa
Portugal	Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E. - Departmento de Hematologia	Lisboa
Portugal	Serviço de Onco-hematologia, Instituto Português de Oncologia do Porto Franscisco Gentil, EPE	Porto
Puerto Rico	San Juan VA Medical Center	San Juan
Romania	Spitalul clinic de urgenta	Brasov
Romania	Institutul Clinic Fundeni Clinica de Hematologie	Bucuresti
Romania	Spitalul Universitar de Urgenta Hematologie	Bucuresti
Romania	Spitalul Clinic judetean de urgenta "Sf. Spiridon, Clinica Hematologie	Iasi
Romania	Spitalul Clinic judetean de urgenta Mures	Targu Mures
Russian Federation	Arkhangelsk Region Clinical Hospital	Arghangelsk
Russian Federation	Altay Regional Oncology Dispensary	Barnaul
Russian Federation	Belgorod Regional Oncology Center	Belgorod
Russian Federation	Cheliabinsk Regional Oncology Dispensary	Cheliabinsk
Russian Federation	Ekaterinburg City Clinical Hospital #7	Ekaterinburg
Russian Federation	1st Republican Clinical Hospital of Udmurtia	Izhevsk
Russian Federation	Cancer Research Center	Moscow
Russian Federation	City Oncology Hospital #62	Moscow
Russian Federation	Moscow Region Clinical Research Institute	Moscow
Russian Federation	S.P. Botkin Moscow City Clinical Hospital	Moscow
Russian Federation	Semashko Central Clinical Hospital #2	Moscow
Russian Federation	Nizhniy Novgorod Region Clinical Hospital	Nizhniy Novgorod
Russian Federation	Novosibirsk State Medical University	Novosibirsk
Russian Federation	Novosibirsk State Regional Clinical Hospital	Novosibirsk
Russian Federation	Medical Scientifical Radiology Center	Obninsk
Russian Federation	Republikan Hospital named after V.A. Baranov	Petrozavodsk
Russian Federation	Saint Petersburg Pavlov State Medical University	Saint Petersburg
Russian Federation	Saratov State Medical University	Saratov
Russian Federation	St. Petersburg City Hospital #31	St. Petersburg
Russian Federation	St. Petersburg Clinical Research Institute of Hematology and Transfusiology	St. Petersburg
Russian Federation	Tomsk Research Oncology Institute	Tomsk
Russian Federation	Republican Clinical Hospital of Bashkorkostan	Ufa
Slovakia	FN F.D. Roosevelt - Oddelenie hematologie	Banska Bysterica
Slovakia	Fakultna nemocnica L. Pasteura - Klinika hematologie a onkohematologie	Kosice
Slovakia	Vychodoslovensky Onkologicky Ustave, a.s.	Kosice
Slovakia	Martinska FN, Klinika hematologie a transfuziologie	Martin
South Africa	Mary Potter Oncology Centre - Little Company of Mary Hospital	Groenkloof, Pretoria
South Africa	Chris Hani Baragwanath Hospital	Johannesburg
South Africa	GVI Oncology Clinical Trial Unit	Panorama	Cape Town
South Africa	East Cape Oncology Centre - St. Georges Hospital	Port Elizabeth
Spain	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
Sweden	Onkologiska kliniken Universitetssjukhuset	Lund
Sweden	Centrum for Hematologi Karolinska University Hospital	Stockholm
Sweden	Hematologiska kliniken M54 Karolinska University Hospital	Stockholm
Thailand	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
Ukraine	Cherkassy Regional Oncology Dispensary	Cherkassy
Ukraine	Dnepropetrovsk Regional Clinical Oncology Dispensary	Dnepropetrovsk
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	Krivoy Rog
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	Zhitomir
United Kingdom	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 States	Central Hematology Oncology Medical Group, Inc	Alhambra	California
United States	Emory Univeersity ,Winship Cancer Institute	Atlanta	Georgia
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Sinai Hospital	Baltimore	Maryland
United States	Providence Saint Joseph Medical Center	Burbank	California
United States	North Idaho Cancer Center	Coeur D Alene	Idaho
United States	South Carolina Oncology Associates	Columbia	South Carolina
United States	South Carolina Oncology Associates, PA	Columbia	South Carolina
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	St. Jude Heritage Medical Group	Fullerton	California
United States	Southeastern Medical Oncology Center	Goldsboro	North Carolina
United States	Hattiesburg Clinic	Hattesburg	Missouri
United States	Oncology Consultants	Houston	Texas
United States	Investigative Clinical Research of Indiana	Indianapolis	Indiana
United States	Integrated Community Oncology Network	Jacksonville	Florida
United States	Kansas City Cancer Center, LLC	Kansas City	Kansas
United States	Wilshire Oncology Medical Group, Inc.	La Verne	California
United States	Lancaster Cancer Center, Ltd.	Lancaster	Pennsylvania
United States	Suburban Hematology-Oncology Associates	Lawrenceville	Georgia
United States	Pacific Shores Medical Group	Long Beach	California
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Louisville Oncology	Louisville	Kentucky
United States	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia
United States	Hematology & Oncology Specialists	Metairie	Louisiana
United States	Innovative Clinical Research of South Florida	Miami	Florida
United States	Medical College of Wisconsin Milwaukee	Milwaukee	Wisconsin
United States	North Valley Hematology Oncology	Mission Hills	California
United States	Vanderbilt University	Nashville	Tennessee
United States	Norwalk Medical Group	Norwalk	Connecticut
United States	East Alabama Medical Center	Opelika,	Alabama
United States	University of California, Irvine Medical Center	Orange	California
United States	Ventura County Hematology-Oncology Specialists	Oxnard	California
United States	The Western Pennsylvania Hospital	Pittsburg	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Cancer Care Associates Medical Group, Inc.	Redondo Beach	California
United States	South Texas Oncology and Hematology	San Antonio	Texas
United States	Central Coast Medical Oncology Corporation	Santa Maria	California
United States	Siouxland Hematolgoy-Oncology Associates	Sioux City	Iowa
United States	Hematology Oncology PC	Stamford	Connecticut
United States	Palm Beach Cancer Institute	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Cyprus,  Czech Republic,  Finland,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Mexico,  New Zealand,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Slovakia,  South Africa,  Spain,  Sweden,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	Progression free survival is defined as time from randomization to progressive disease or death due to any cause, whichever occurs first.	Subjects are followed until progressive disease/death or the end of the study. The median follow up time is 33.9 months.	No
Secondary	Overall Response Rate	Overall response rate is defined as Complete Response (CR) + Complete Response Unconfirmed (CRu) + Partial Response (PR) using International Working Group Criteria (IWGC) and Independent Radiographic Review results and clinical results. The IWGC CR requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms, and normalization of lactic dehydrogenase and bone marrow involvement. CRu requires more than 75% reduction in sum of product of nodes (SPD). PR requires moer than 50% reduction in SPD.	Subjects are followed until progressive disease/death or the end of the study. The median follow up time is 33.9 months.	No