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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00312845




Registration number
NCT00312845
Ethics application status
Date submitted
7/04/2006
Date registered
11/04/2006
Date last updated
25/06/2012

Titles & IDs
Public title
Study of VELCADE and Rituximab in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
Scientific 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
Secondary ID [1] 0 0
26866138-LYM-3001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Hodgkin's Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bortezomib + Rituximab
Treatment: Drugs - Rituximab

Experimental: Bortezomib + Rituximab -

Active comparator: Rituximab -


Treatment: Drugs: 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.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival
Timepoint [1] 0 0
Subjects are followed until progressive disease/death or the end of the study. The median follow up time is 33.9 months.
Secondary outcome [1] 0 0
Overall Response Rate
Timepoint [1] 0 0
Subjects are followed until progressive disease/death or the end of the study. The median follow up time is 33.9 months.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2010
Sample size
Target
Accrual to date
Final
676
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [4] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [6] 0 0
Fremantle Hospital - Fremantle
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3002 - East Melbourne
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment postcode(s) [6] 0 0
6160 - Fremantle
Recruitment outside Australia
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United States of America
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Alabama
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California
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Connecticut
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Georgia
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Idaho
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Indiana
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Kansas
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Kentucky
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Louisiana
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Maryland
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Missouri
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North Carolina
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Oregon
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Wisconsin
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Argentina
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La Plata - Buenos Aires
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Argentina
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Mendoza
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Belgium
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Anderlecht
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Belgium
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Antwerpen
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Belgium
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Brugge
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Bruxelles
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Belgium
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Charleroi
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Belgium
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Edegem
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Gent
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Hasselt
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Liege
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Roeselare
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Brazil
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Rio Grande do Sul
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Hamilton
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Sichuan
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Beijing
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China
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Guangzhou
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China
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Haidian District Beijing
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Shanghai
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Cyprus
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Nikosia
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Czech Republic
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Brno
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Czech Republic
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Hradec Kralove
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Czech Republic
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Olomouc
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Czech Republic
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Praha
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Finland
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Lahti
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Finland
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Pori
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France
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Bordeaux
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France
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Le Mans
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France
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Lille
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France
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Lyon
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France
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Nantes
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France
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Pessac
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France
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Pierre Benite
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Germany
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Herrsching
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Germany
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Munster
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Germany
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Würzburg
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Greece
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Athens
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Rio Patras
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Hungary
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Debrecen
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Gyor
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Hungary
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Szeged
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India
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Bangalore
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India
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Chandigarh
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India
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Chennai
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India
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Hyderabaad
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India
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Jaipur
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India
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Jubilee Hills
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Karnataka
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Kerala
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Mumbai
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Israel
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Beer Sheva
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Haifa
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Jerusalem
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Petah Tikva
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Tel Aviv
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Tel HaShomer
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Bologna
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Perugia
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Roma
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Torino
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Korea, Republic of
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Gyeonggi-Do
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Korea, Republic of
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Ilmon-Dong, Kangnam-Ku, Seoul
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Korea, Republic of
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Ilsandong-Gu, Goyang-Si, and Gyeonggi-Do
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Korea, Republic of
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Ilwon dong, Kangnam-Ku, Seoul
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Korea, Republic of
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Seoul
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Mexico
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Delagacion Tlalpan
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Mexico
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Monterrey, Nuevo leon
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New Zealand
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Christchurch
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Poland
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Gdansk
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Krakow
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Lodz
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Lublin
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Warsawa
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Warszawa
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Wroclaw
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Portugal
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Coimbra
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Portugal
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Lisboa
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Portugal
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Porto
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Puerto Rico
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San Juan
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Romania
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Brasov
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Romania
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Bucuresti
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Romania
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Iasi
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Romania
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Targu Mures
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Russian Federation
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Arghangelsk
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Russian Federation
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Barnaul
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Belgorod
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Cheliabinsk
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Ekaterinburg
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Izhevsk
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Russian Federation
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Moscow
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Russian Federation
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Nizhniy Novgorod
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Russian Federation
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Novosibirsk
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Russian Federation
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Obninsk
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Russian Federation
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Petrozavodsk
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Russian Federation
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Saint Petersburg
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Russian Federation
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Saratov
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Russian Federation
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St. Petersburg
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Russian Federation
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Tomsk
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Russian Federation
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Ufa
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Slovakia
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Banska Bysterica
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Slovakia
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Kosice
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Slovakia
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Martin
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South Africa
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Cape Town
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South Africa
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Groenkloof, Pretoria
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South Africa
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Johannesburg
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South Africa
State/province [129] 0 0
Port Elizabeth
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Salamanca
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Sweden
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Lund
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Sweden
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Stockholm
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Thailand
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Bangkok
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Thailand
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Chiang Mai
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Ukraine
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Cherkassy
Country [138] 0 0
Ukraine
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Dnepropetrovsk
Country [139] 0 0
Ukraine
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Donetsk
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Ukraine
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Khmelnitsky
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Ukraine
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Kiev
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Ukraine
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Krivoy Rog
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Ukraine
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Lviv
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Ukraine
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Poltava
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Ukraine
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Simferopol
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Ukraine
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Zhitomir
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United Kingdom
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Aberdeen
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United Kingdom
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Cambridge
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United Kingdom
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Cardiff
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United Kingdom
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London
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United Kingdom
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Plymouth
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United Kingdom
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Taunton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Millennium Pharmaceuticals, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00312845
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Millennium Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00312845