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

• Sponsor: Millennium Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00312845
• Collaborator: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Enrollment: 676
• Locations: 206
• Arms: 2
• Duration (Months): 52
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Drug: Bortezomib + Rituximab; Drug: Rituximab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 676 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bortezomib + Rituximab	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.
Active Comparator: Rituximab	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).

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [Subjects are followed until progressive disease/death or the end of the study. The median follow up time is 33.9 months.]

   Progression free survival is defined as time from randomization to progressive disease or death due to any cause, whichever occurs first.

Secondary Outcome Measures

1. Overall Response Rate [Subjects are followed until progressive disease/death or the end of the study. The median follow up time is 33.9 months.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	East Alabama Medical Center	Opelika,	Alabama	United States
2	Central Hematology Oncology Medical Group, Inc	Alhambra	California	United States	91801
3	Comprehensive Blood and Cancer Center	Bakersfield	California	United States	93309
4	Providence Saint Joseph Medical Center	Burbank	California	United States	91505
5	St. Jude Heritage Medical Group	Fullerton	California	United States	92835
6	Wilshire Oncology Medical Group, Inc.	La Verne	California	United States	91790
7	Pacific Shores Medical Group	Long Beach	California	United States	90813
8	University of Southern California	Los Angeles	California	United States	90033
9	University of California, Los Angeles	Los Angeles	California	United States	90095
10	North Valley Hematology Oncology	Mission Hills	California	United States	91345
11	University of California, Irvine Medical Center	Orange	California	United States	92868
12	Ventura County Hematology-Oncology Specialists	Oxnard	California	United States	93030
13	Cancer Care Associates Medical Group, Inc.	Redondo Beach	California	United States	90277
14	Central Coast Medical Oncology Corporation	Santa Maria	California	United States	93454
15	Norwalk Medical Group	Norwalk	Connecticut	United States
16	Hematology Oncology PC	Stamford	Connecticut	United States
17	Integrated Community Oncology Network	Jacksonville	Florida	United States
18	Innovative Clinical Research of South Florida	Miami	Florida	United States
19	Palm Beach Cancer Institute	West Palm Beach	Florida	United States
20	Emory Univeersity ,Winship Cancer Institute	Atlanta	Georgia	United States
21	Suburban Hematology-Oncology Associates	Lawrenceville	Georgia	United States	30045
22	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia	United States	30060
23	North Idaho Cancer Center	Coeur D Alene	Idaho	United States
24	Investigative Clinical Research of Indiana	Indianapolis	Indiana	United States
25	Siouxland Hematolgoy-Oncology Associates	Sioux City	Iowa	United States
26	Kansas City Cancer Center, LLC	Kansas City	Kansas	United States	66210
27	Louisville Oncology	Louisville	Kentucky	United States
28	Hematology & Oncology Specialists	Metairie	Louisiana	United States
29	Sinai Hospital	Baltimore	Maryland	United States
30	Hattiesburg Clinic	Hattesburg	Missouri	United States
31	Southeastern Medical Oncology Center	Goldsboro	North Carolina	United States	27530
32	Oregon Health & Science University	Portland	Oregon	United States
33	Lancaster Cancer Center, Ltd.	Lancaster	Pennsylvania	United States	17601
34	The Western Pennsylvania Hospital	Pittsburg	Pennsylvania	United States
35	South Carolina Oncology Associates, PA	Columbia	South Carolina	United States	29210
36	South Carolina Oncology Associates	Columbia	South Carolina	United States
37	Vanderbilt University	Nashville	Tennessee	United States	37232
38	The Center for Cancer and Blood Disorders	Fort Worth	Texas	United States
39	Oncology Consultants	Houston	Texas	United States	777024
40	South Texas Oncology and Hematology	San Antonio	Texas	United States
41	Medical College of Wisconsin Milwaukee	Milwaukee	Wisconsin	United States
42	Higa San Martin	La Plata - Buenos Aires		Argentina
43	Hospital Professor Rodolfo Rossi	La Plata - Buenos Aires		Argentina
44	Centro Oncologico Integracion Regional	Mendoza		Argentina
45	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
46	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
47	Peter MacCallum Cancer Institute	East Melbourne	Victoria	Australia	3002
48	Alfred Hospital	Melbourne	Victoria	Australia	3004
49	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
50	Fremantle Hospital	Fremantle	Western Australia	Australia	6160
51	ULB Erasme	Anderlecht		Belgium	1070
52	AZ Stuivenberg	Antwerpen		Belgium	2060
53	AZ Sint Jan	Brugge		Belgium	8000
54	Institute J. Bordet	Bruxelles		Belgium	1000
55	Clinique Notre Dame	Charleroi		Belgium	6000
56	UZ Antwerpen - Universitair Ziekenhuis Antwerpen	Edegem		Belgium	2650
57	UZ Gent - Universitair Ziekenhuis Gent	Gent		Belgium	9000
58	Virga Jesse Ziekenhuis, Dienst Hematologie	Hasselt		Belgium	3500
59	CHR La Citadelle	Liege		Belgium	4000
60	CHU Sart Tilman	Liege		Belgium	4000
61	Heilig Hart Roeselare	Roeselare		Belgium	8800
62	Servico de Oncologia do Hospital Sao Lucas da PUC do rio Grande do Sul	Porto Alegre	Rio Grande do Sul	Brazil	90610-00
63	Instituto Nacional de Cancer	Rio de Janeiro		Brazil	20231-050
64	Hospital Brigadeiro	Sao Paulo		Brazil	01404-901
65	Faculdade de Medicina do ABC	Sao Paulo		Brazil	09060-650
66	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario	Canada
67	University Health Network - Princess Margaret Hospital	Toronto	Ontario	Canada
68	Juravinski Cancer Centre	Hamilton		Canada
69	West China Hospital of Sichuan	Chengdu	Sichuan	China	610041
70	Cancer Hospital (Institute), CAMS&PUMC	Beijing		China	100021
71	Beijing Cancer Hospital	Beijing		China	100036
72	Peking University People's Hospital	Beijing		China	100044
73	Affiliated Hospital of the Academy of Military Medical Sciences	Beijing		China	100071
74	Cancer Center, Sun Yat-Sen University	Guangzhou		China	510060
75	Peking University Third Hospital	Haidian District Beijing		China	100083
76	RuiJin Hospital	Shanghai		China	200025
77	Cancer Hospital - FuDan University	Shanghai		China	200032
78	Bank of Cyprus Oncology Centre	Nikosia		Cyprus	2006
79	Fakultni nemocnice Brno	Brno		Czech Republic	625 00
80	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czech Republic	500 05
81	Fakultni nemocnice Olomouc	Olomouc		Czech Republic	775 20
82	Vseobecna Fakultni Nemocnice	Praha		Czech Republic	2
83	Paijat - Hameen Keskussairaala	Lahti		Finland	15850
84	Satakunnan Keskussairaala	Pori		Finland	28500
85	Institut Bergonie	Bordeaux		France	33076
86	Clinique Victor Hugo	Le Mans		France	72015
87	Hopital Claude Huriez	Lille		France	59037
88	Centre Léon Bérard	Lyon		France	69373
89	Hopital Hotel Dieu	Nantes		France	44098
90	Service des Maladies due sang - Hopital haut Leveque	Pessac		France	33604
91	Centre Hospitalier Lyon Sud	Pierre Benite		France	69495
92	Onkologische Schwerpunktpraxis	Herrsching		Germany	82211
93	Universitatsklinikum Munster - Klinik fur Innere Medizin	Munster		Germany
94	Praxis für Hämetologie und Oncologie	Würzburg		Germany	97070
95	Laiko General Hospital of Athens - 1st Internist Clinic - Hematology Department	Athens		Greece	11527
96	University General Hospital Attikon - 2nd Department of Internal Medicine - Propedeutic & Research Institute	Athens		Greece	12462
97	University Hospital of Patras - Department of Internal Medicine - Hematology Division	Rio Patras		Greece	26500
98	Debreceni Egyetem, Orvos- es Egeszsegtudomanyl Centrum, iii. Belgyogyaszati Klinika	Debrecen		Hungary	H-4004
99	Petz Aladar County Hospital	Gyor		Hungary	9024
100	SZEgedi Tudomanyegyetem, II Belgyaszati Klinika	Szeged		Hungary	H-6720
101	Institution Manipal Hospital	Bangalore		India
102	Postgraduate Institute of Medical Education and Research	Chandigarh		India	160 012
103	Apollo Speciality Hospital	Chennai		India	6000035
104	Nizam's Institute of Medical Sciences	Hyderabaad		India	500 082
105	SMS Medical College Hospital	Jaipur		India	302 004
106	Apollo Hospitals, Hyderabad Apollo Hospital Complex	Jubilee Hills		India
107	Shirdi Saibaba Cancer Hospital	Karnataka		India	576 104
108	Department of Medical Oncology - Regional Cancer Centre	Kerala		India
109	Regional Cancer Centre	Kerala		India
110	Tata Memorial Centre	Mumbai		India	400 012
111	Soroka Medical Center	Beer Sheva		Israel
112	Rambam Medical Center	Haifa		Israel
113	Hadassah Medical Center	Jerusalem		Israel
114	Rabin Medical Center	Petah Tikva		Israel
115	Sorraski Tel Aviv Medical Center	Tel Aviv		Israel
116	Sheba Medical Center	Tel HaShomer		Israel
117	Azienda Ospedaliero Universitaria di Bologna	Bologna		Italy	40138
118	Universita degli Studi di Perugia	Perugia		Italy	06122
119	Azienda Ospedallera Universitaria Policlinico Tor Vergata	Roma		Italy	00133
120	Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista	Torino		Italy	10126
121	Lung Cancer Center - National Cancer Center	Gyeonggi-Do		Korea, Republic of	411-769
122	Samsung Medical Center - Division of Hematology-Oncology, Department of Medicine	Ilmon-Dong, Kangnam-Ku, Seoul		Korea, Republic of	135-710
123	Hematology-Oncology Clinic, Center for Specific Organs Cancer - National Cancer Center	Ilsandong-Gu, Goyang-Si, and Gyeonggi-Do		Korea, Republic of	410-769
124	Samsung Medical Center - Department of Internal Medicine	Ilwon dong, Kangnam-Ku, Seoul		Korea, Republic of	135-710
125	Severance Hospital, Yonsei University College of Medicine	Seoul		Korea, Republic of	120-752
126	Asan Medical Center	Seoul		Korea, Republic of	138-736
127	Instituto Nacional De Ciencias Medicas Y Nutricion Salvador Zubiran	Delagacion Tlalpan		Mexico	14000
128	Instituto Nacional De Cancerologia Incan	Delagacion Tlalpan		Mexico	14080
129	Hospital Universitario Dr. Jose Eleuterio Gonzalez UANL	Monterrey, Nuevo leon		Mexico	64460
130	Canterbury Health Laboratories	Christchurch		New Zealand
131	Klinika Hematologii Instytut Chorob Wewnetrznych	Gdansk		Poland	80-952
132	Klinika Hematologii CMUJ	Krakow		Poland	31-501
133	Klinika Hematologii - Uniwersytetu Medycznego	Lodz		Poland	93-510
134	Klinika Hematologii i Transplantologii Szpiku AM	Lublin		Poland	20-081
135	Wojskowy Instytut Medyczny - Klinika Hematologii	Warsawa		Poland	00-909
136	Instytut Hematologii i Transfuzjologii	Warszawa		Poland	00-957
137	Klinika Hematologii AM	Warszawa		Poland	02-097
138	Klinika Nowotworow Ukladu Chlonnego	Warszawa		Poland	02-781
139	Katedra i Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku	Wroclaw		Poland	50-367
140	Servico de Hematologia - Hospital de Dia - Hospital Da Universidade de Coimbra	Coimbra		Portugal	3000-075
141	Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E. - Departmento de Hematologia	Lisboa		Portugal	1099-023
142	Hospital de Dia de Hematologia - Hospital de Santa Maria E.P.E.	Lisboa		Portugal	1649-035
143	Serviço de Onco-hematologia, Instituto Português de Oncologia do Porto Franscisco Gentil, EPE	Porto		Portugal	4200-072
144	San Juan VA Medical Center	San Juan		Puerto Rico	00921
145	Spitalul clinic de urgenta	Brasov		Romania
146	Institutul Clinic Fundeni Clinica de Hematologie	Bucuresti		Romania
147	Spitalul Universitar de Urgenta Hematologie	Bucuresti		Romania
148	Spitalul Clinic judetean de urgenta "Sf. Spiridon, Clinica Hematologie	Iasi		Romania
149	Spitalul Clinic judetean de urgenta Mures	Targu Mures		Romania
150	Arkhangelsk Region Clinical Hospital	Arghangelsk		Russian Federation	163045
151	Altay Regional Oncology Dispensary	Barnaul		Russian Federation	656049
152	Belgorod Regional Oncology Center	Belgorod		Russian Federation	308010
153	Cheliabinsk Regional Oncology Dispensary	Cheliabinsk		Russian Federation	454087
154	Ekaterinburg City Clinical Hospital #7	Ekaterinburg		Russian Federation	620137
155	1st Republican Clinical Hospital of Udmurtia	Izhevsk		Russian Federation	426039
156	Cancer Research Center	Moscow		Russian Federation	115478
157	S.P. Botkin Moscow City Clinical Hospital	Moscow		Russian Federation	125101
158	Moscow Region Clinical Research Institute	Moscow		Russian Federation	129110
159	Semashko Central Clinical Hospital #2	Moscow		Russian Federation	129128
160	City Oncology Hospital #62	Moscow		Russian Federation	143423
161	Nizhniy Novgorod Region Clinical Hospital	Nizhniy Novgorod		Russian Federation	603129
162	Novosibirsk State Regional Clinical Hospital	Novosibirsk		Russian Federation	630087
163	Novosibirsk State Medical University	Novosibirsk		Russian Federation	630091
164	Medical Scientifical Radiology Center	Obninsk		Russian Federation	249020
165	Republikan Hospital named after V.A. Baranov	Petrozavodsk		Russian Federation	185019
166	Saint Petersburg Pavlov State Medical University	Saint Petersburg		Russian Federation	197022
167	Saratov State Medical University	Saratov		Russian Federation	410028
168	St. Petersburg Clinical Research Institute of Hematology and Transfusiology	St. Petersburg		Russian Federation	191024
169	St. Petersburg City Hospital #31	St. Petersburg		Russian Federation	197110
170	Tomsk Research Oncology Institute	Tomsk		Russian Federation	634028
171	Republican Clinical Hospital of Bashkorkostan	Ufa		Russian Federation	450005
172	FN F.D. Roosevelt - Oddelenie hematologie	Banska Bysterica		Slovakia	97517
173	Fakultna nemocnica L. Pasteura - Klinika hematologie a onkohematologie	Kosice		Slovakia	040 11
174	Vychodoslovensky Onkologicky Ustave, a.s.	Kosice		Slovakia	041 90
175	Martinska FN, Klinika hematologie a transfuziologie	Martin		Slovakia	036 59
176	GVI Oncology Clinical Trial Unit	Panorama	Cape Town	South Africa
177	Mary Potter Oncology Centre - Little Company of Mary Hospital	Groenkloof, Pretoria		South Africa	0181
178	Chris Hani Baragwanath Hospital	Johannesburg		South Africa
179	East Cape Oncology Centre - St. Georges Hospital	Port Elizabeth		South Africa
180	Hospital Durans I Reynals - Institut Catala d'Oncologia	Barcelona		Spain	08907
181	Hospital Germans Trias i Pujol Institut Catala d'Oncologia	Barcelona		Spain	08916
182	Hospital Universitario La Paz	Madrid		Spain	28046
183	Hospital Universitario de Salamanca	Salamanca		Spain	37007
184	Onkologiska kliniken Universitetssjukhuset	Lund		Sweden
185	Centrum for Hematologi Karolinska University Hospital	Stockholm		Sweden
186	Hematologiska kliniken M54 Karolinska University Hospital	Stockholm		Sweden
187	King Chulalongkorn Memorial Hospital	Bangkok		Thailand	10330
188	Ramathibodi Hospital, Mahidol University	Bangkok		Thailand	10400
189	Siriraj Hospital, Mahidol University	Bangkok		Thailand	10700
190	Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University	Chiang Mai		Thailand	50200
191	Cherkassy Regional Oncology Dispensary	Cherkassy		Ukraine	18009
192	Dnepropetrovsk Regional Clinical Oncology Dispensary	Dnepropetrovsk		Ukraine	46055
193	Institute for Emergency and Urgent Medical Assistance named after V.K. Gusak of AMS of Ukraine	Donetsk		Ukraine	83045
194	Khmelnitskiy Regional Hopsital	Khmelnitsky		Ukraine	29000
195	Kiev Center of Marrow Transplantaion	Kiev		Ukraine	03115
196	Krivoy Rog Oncology Dispensary	Krivoy Rog		Ukraine
197	Institute of Blood Pathology and Transfusional Medicine of AMS of Ukraine, Lviv Clinical Hospital #5	Lviv		Ukraine	79044
198	Ukrainian Medical Stomatological Academy, Poltava Regional Dispensary	Poltava		Ukraine	36024
199	Crimean Republic Clinical Oncology Dispensary	Simferopol		Ukraine
200	Zhitomir Gerbachevsky Regional Clinical Hospital	Zhitomir		Ukraine	10002
201	Aberdeen Royal Infirmary - Department of Haematology	Aberdeen		United Kingdom
202	Addenbrooke's Hospital - Department of Haematology	Cambridge		United Kingdom	CB2 2QQ
203	University Hospital of Wales	Cardiff		United Kingdom	CF14 4XN
204	Guy's & St. Thomas Hospital	London		United Kingdom	SE1 9RT
205	Derriford Hospital - Department of Haematology	Plymouth		United Kingdom	PL6 8DH
206	Taunton & Somerset Hospital	Taunton		United Kingdom	TA1 5DA

Sponsors and Collaborators

• Millennium Pharmaceuticals, Inc.
• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

• Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00312845
• Other Study ID Numbers: 26866138-LYM-3001
• First Posted: Apr 11, 2006
• Last Update Posted: Jun 25, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by Millennium Pharmaceuticals, Inc.: B-cell Non-Hodgkin's Lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Rituximab; Bortezomib

Study Results

Participant Flow

Arm/Group Title	Bortezomib + Rituximab	Rituximab
Arm/Group Description	1.6 mg/m^2 VELCADE for Injection administered weekly on Days 1, 8, 15, and 22 of a 35-day cycle in combination with 4 doses of 375 mg/m^2 rituximab once weekly on Days 1, 8, 15, and 22 of Cycle 1 and a single dose of 375 mg/m^2 rituximab on Day 1 of Cycles 2 through 5 (for a total of 8 doses of rituximab).	375 mg/m^2 rituximab once weekly on Days 1, 8, 15, and 22 of Cycle 1, and as a single dose of 375 mg/m^2 on Day 1 of Cycles 2 through 5 (for a total of 8 doses).
Period Title: Overall Study
STARTED	336	340
COMPLETED	237	245
NOT COMPLETED	99	95

Baseline Characteristics

Arm/Group Title	Bortezomib + Rituximab	Rituximab	Total
Arm/Group Description	1.6 mg/m^2 VELCADE for Injection administered weekly on Days 1, 8, 15, and 22 of a 35-day cycle in combination with 4 doses of 375 mg/m^2 rituximab once weekly on Days 1, 8, 15, and 22 of Cycle 1 and a single dose of 375 mg/m^2 rituximab on Day 1 of Cycles 2 through 5 (for a total of 8 doses of rituximab).	375 mg/m^2 rituximab once weekly on Days 1, 8, 15, and 22 of Cycle 1, and as a single dose of 375 mg/m^2 on Day 1 of Cycles 2 through 5 (for a total of 8 doses).	Total of all reporting groups
Overall Participants	336	340	676
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	243 72.3%	242 71.2%	485 71.7%
>=65 years	93 27.7%	98 28.8%	191 28.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.8 (11.12)	57.3 (12)	57 (11.56)
Sex: Female, Male (Count of Participants)
Female	164 48.8%	203 59.7%	367 54.3%
Male	172 51.2%	137 40.3%	309 45.7%
Region of Enrollment (participants) [Number]
United States	14 4.2%	16 4.7%	30 4.4%
Portugal	11 3.3%	12 3.5%	23 3.4%
Slovakia	7 2.1%	8 2.4%	15 2.2%
Greece	1 0.3%	1 0.3%	2 0.3%
Thailand	2 0.6%	1 0.3%	3 0.4%
Spain	9 2.7%	5 1.5%	14 2.1%
Ukraine	13 3.9%	11 3.2%	24 3.6%
Israel	7 2.1%	7 2.1%	14 2.1%
Russian Federation	52 15.5%	55 16.2%	107 15.8%
Italy	14 4.2%	15 4.4%	29 4.3%
India	17 5.1%	24 7.1%	41 6.1%
France	13 3.9%	10 2.9%	23 3.4%
Australia	5 1.5%	3 0.9%	8 1.2%
South Africa	2 0.6%	2 0.6%	4 0.6%
China	46 13.7%	40 11.8%	86 12.7%
Korea, Republic of	4 1.2%	3 0.9%	7 1%
Finland	1 0.3%	2 0.6%	3 0.4%
United Kingdom	9 2.7%	10 2.9%	19 2.8%
Hungary	3 0.9%	6 1.8%	9 1.3%
Czech Republic	18 5.4%	17 5%	35 5.2%
Mexico	9 2.7%	8 2.4%	17 2.5%
Canada	9 2.7%	10 2.9%	19 2.8%
Argentina	2 0.6%	5 1.5%	7 1%
Brazil	18 5.4%	21 6.2%	39 5.8%
Belgium	18 5.4%	19 5.6%	37 5.5%
Poland	24 7.1%	21 6.2%	45 6.7%
Romania	6 1.8%	2 0.6%	8 1.2%
Germany	0 0%	3 0.9%	3 0.4%
Sweden	2 0.6%	3 0.9%	5 0.7%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival
Description	Progression free survival is defined as time from randomization to progressive disease or death due to any cause, whichever occurs first.
Time Frame	Subjects are followed until progressive disease/death or the end of the study. The median follow up time is 33.9 months.

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population is defined as all patients randomized to the trial.

Arm/Group Title	Bortezomib + Rituximab	Rituximab
Arm/Group Description	1.6 mg/m^2 VELCADE for Injection administered weekly on Days 1, 8, 15, and 22 of a 35-day cycle in combination with 4 doses of 375 mg/m^2 rituximab once weekly on Days 1, 8, 15, and 22 of Cycle 1 and a single dose of 375 mg/m^2 rituximab on Day 1 of Cycles 2 through 5 (for a total of 8 doses of rituximab).	375 mg/m^2 rituximab once weekly on Days 1, 8, 15, and 22 of Cycle 1, and as a single dose of 375 mg/m^2 on Day 1 of Cycles 2 through 5 (for a total of 8 doses).
Measure Participants	336	340
Median (95% Confidence Interval) [days]	389	334

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bortezomib + Rituximab, Rituximab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.039
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Overall Response Rate
Description	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.
Time Frame	Subjects are followed until progressive disease/death or the end of the study. The median follow up time is 33.9 months.

Outcome Measure Data

Analysis Population Description

The response-evaluable population was defined as all subjects in the ITT population who received at least 1 dose of VELCADE or rituximab, had at least 1 measurable tumor mass (>1.5 cm in the longest dimension and >1.0 cm in the short axis) at baseline, and had at least 1 post-baseline disease assessment by independent radiology reviewers/IRC.

Arm/Group Title	Bortezomib + Rituximab	Rituximab
Arm/Group Description	1.6 mg/m^2 VELCADE for Injection administered weekly on Days 1, 8, 15, and 22 of a 35-day cycle in combination with 4 doses of 375 mg/m^2 rituximab once weekly on Days 1, 8, 15, and 22 of Cycle 1 and a single dose of 375 mg/m^2 rituximab on Day 1 of Cycles 2 through 5 (for a total of 8 doses of rituximab).	375 mg/m^2 rituximab once weekly on Days 1, 8, 15, and 22 of Cycle 1, and as a single dose of 375 mg/m^2 on Day 1 of Cycles 2 through 5 (for a total of 8 doses).
Measure Participants	315	324
Number [participants]	199 59.2%	160 47.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bortezomib + Rituximab, Rituximab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

Time Frame	the end of study
Arm/Group Title	Bortezomib + Rituximab		Rituximab
Arm/Group Description	1.6 mg/m^2 VELCADE for Injection administered weekly on Days 1, 8, 15, and 22 of a 35-day cycle in combination with 4 doses of 375 mg/m^2 rituximab once weekly on Days 1, 8, 15, and 22 of Cycle 1 and a single dose of 375 mg/m^2 rituximab on Day 1 of Cycles 2 through 5 (for a total of 8 doses of rituximab).		375 mg/m^2 rituximab once weekly on Days 1, 8, 15, and 22 of Cycle 1, and as a single dose of 375 mg/m^2 on Day 1 of Cycles 2 through 5 (for a total of 8 doses).
All Cause Mortality
	Bortezomib + Rituximab		Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bortezomib + Rituximab		Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/334 (17.7%)		37/339 (10.9%)
Blood and lymphatic system disorders
Febrile neutropenia	5/334 (1.5%)		3/339 (0.9%)
Neutropenia	2/334 (0.6%)		2/339 (0.6%)
Bone marrow failure	0/334 (0%)		1/339 (0.3%)
Leukopenia	0/334 (0%)		1/339 (0.3%)
Anaemia	1/334 (0.3%)		0/339 (0%)
Lymphadenopathy	1/334 (0.3%)		0/339 (0%)
Cardiac disorders
Left entricular dysfunction	0/334 (0%)		1/339 (0.3%)
Palpitations	0/334 (0%)		1/339 (0.3%)
Pericardial effusion	0/334 (0%)		1/339 (0.3%)
Right ventricular dysfunction	0/334 (0%)		1/339 (0.3%)
Acute myocardial infarction	1/334 (0.3%)		0/339 (0%)
Angina unstable	1/334 (0.3%)		0/339 (0%)
Cardiac failure acute	1/334 (0.3%)		0/339 (0%)
Cardiogenic shock	1/334 (0.3%)		0/339 (0%)
Coronary artery disease	1/334 (0.3%)		0/339 (0%)
Cyanosis	1/334 (0.3%)		0/339 (0%)
Tachycardia	1/334 (0.3%)		0/339 (0%)
Gastrointestinal disorders
Diarrhoea	5/334 (1.5%)		2/339 (0.6%)
Vomiting	4/334 (1.2%)		1/339 (0.3%)
Abdominal pain	2/334 (0.6%)		2/339 (0.6%)
Colonic obstruction	0/334 (0%)		1/339 (0.3%)
Enteritis	0/334 (0%)		1/339 (0.3%)
Gastrointestinal obstruction	0/334 (0%)		1/339 (0.3%)
Constipation	1/334 (0.3%)		0/339 (0%)
Dysphagia	1/334 (0.3%)		0/339 (0%)
Nausea	1/334 (0.3%)		0/339 (0%)
Periodontitis	1/334 (0.3%)		0/339 (0%)
Toothache	1/334 (0.3%)		0/339 (0%)
General disorders
Pyrexia	6/334 (1.8%)		2/339 (0.6%)
Asthenia	1/334 (0.3%)		2/339 (0.6%)
Chest pain	0/334 (0%)		1/339 (0.3%)
Oedema peripheral	1/334 (0.3%)		1/339 (0.3%)
Pain	0/334 (0%)		1/339 (0.3%)
Chest discomfort	1/334 (0.3%)		0/339 (0%)
Hepatobiliary disorders
Cholangitis acute	0/334 (0%)		1/339 (0.3%)
Cholecystitis acute	0/334 (0%)		1/339 (0.3%)
Cirrhosis alcoholic	0/334 (0%)		1/339 (0.3%)
Immune system disorders
Hypersensitivity	4/334 (1.2%)		1/339 (0.3%)
Anaphylactic reaction	2/334 (0.6%)		0/339 (0%)
Infections and infestations
Pneumonia	7/334 (2.1%)		3/339 (0.9%)
Herpes zoster	4/334 (1.2%)		0/339 (0%)
Sepsis	3/334 (0.9%)		0/339 (0%)
Urinary tract infection	0/334 (0%)		2/339 (0.6%)
Bronchopneumonia	0/334 (0%)		1/339 (0.3%)
Clostridial infection	0/334 (0%)		1/339 (0.3%)
Empyema	0/334 (0%)		1/339 (0.3%)
Laryngitis	0/334 (0%)		1/339 (0.3%)
Lower respiratory tract infection	1/334 (0.3%)		1/339 (0.3%)
Meningitis	0/334 (0%)		1/339 (0.3%)
Necrotixing fasciitis	0/334 (0%)		1/339 (0.3%)
Pharyngitis	0/334 (0%)		1/339 (0.3%)
Tracheobronchitis	0/334 (0%)		1/339 (0.3%)
Aspergillosis	1/334 (0.3%)		0/339 (0%)
Gastroenteritis salmonella	1/334 (0.3%)		0/339 (0%)
Hepatitis B	1/334 (0.3%)		0/339 (0%)
Hepatitis viral	1/334 (0.3%)		0/339 (0%)
Herpes virus infection	1/334 (0.3%)		0/339 (0%)
Pyelonephritis	1/334 (0.3%)		0/339 (0%)
Respiratory tract infection	1/334 (0.3%)		0/339 (0%)
Septic shock	1/334 (0.3%)		0/339 (0%)
Upper respiratory tract infection	1/334 (0.3%)		0/339 (0%)
Injury, poisoning and procedural complications
Collapse of lung	0/334 (0%)		1/339 (0.3%)
Concussion	1/334 (0.3%)		0/339 (0%)
Pelvic fracture	1/334 (0.3%)		0/339 (0%)
Upper limb fracture	1/334 (0.3%)		0/339 (0%)
Metabolism and nutrition disorders
Dehydration	2/334 (0.6%)		0/339 (0%)
Decreased appetite	1/334 (0.3%)		0/339 (0%)
Hyperglycaemia	1/334 (0.3%)		0/339 (0%)
Hyperkalaemia	1/334 (0.3%)		0/339 (0%)
Hyponatraemia	1/334 (0.3%)		0/339 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/334 (0%)		1/339 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm	0/334 (0%)		1/339 (0.3%)
Tumour necrosis	0/334 (0%)		1/339 (0.3%)
Rectal cancer	1/334 (0.3%)		0/339 (0%)
Nervous system disorders
Cerebrovascular accident	2/334 (0.6%)		0/339 (0%)
Convulsion	1/334 (0.3%)		1/339 (0.3%)
Dementia	0/334 (0%)		1/339 (0.3%)
Somnolence	0/334 (0%)		1/339 (0.3%)
Loss of consciousness	1/334 (0.3%)		0/339 (0%)
Myelopathy	1/334 (0.3%)		0/339 (0%)
Peripheral sensory neuropathy	1/334 (0.3%)		0/339 (0%)
Syncope	1/334 (0.3%)		0/339 (0%)
Toxic encephalopathy	1/334 (0.3%)		0/339 (0%)
Psychiatric disorders
Confusional state	0/334 (0%)		1/339 (0.3%)
Renal and urinary disorders
Renal failure	2/334 (0.6%)		0/339 (0%)
Calculus urinary	0/334 (0%)		1/339 (0.3%)
Renal failure acute	1/334 (0.3%)		0/339 (0%)
Renal impairment	1/334 (0.3%)		0/339 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/334 (0.6%)		2/339 (0.6%)
Hypoxia	2/334 (0.6%)		0/339 (0%)
Chronic obstructive pulmonary disease	0/334 (0%)		1/339 (0.3%)
Chylothorax	0/334 (0%)		1/339 (0.3%)
Dyspnoea	1/334 (0.3%)		1/339 (0.3%)
Epistaxis	0/334 (0%)		1/339 (0.3%)
Pulmonary embolism	0/334 (0%)		1/339 (0.3%)
Acute respiratory failure	1/334 (0.3%)		0/339 (0%)
Pleural haemorrhage	1/334 (0.3%)		0/339 (0%)
Pneumothorax	1/334 (0.3%)		0/339 (0%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	0/334 (0%)		1/339 (0.3%)
Seborrhoeic dermatitis	0/334 (0%)		1/339 (0.3%)
Urticaria	0/334 (0%)		1/339 (0.3%)
Hyperhidrosis	1/334 (0.3%)		0/339 (0%)
Vascular disorders
Hypotension	4/334 (1.2%)		0/339 (0%)
Deep vein thrombosis	0/334 (0%)		1/339 (0.3%)
Orthostatic hypotension	1/334 (0.3%)		0/339 (0%)
Subclavian vein thrombosis	1/334 (0.3%)		0/339 (0%)
Thrombosis	1/334 (0.3%)		0/339 (0%)
Other (Not Including Serious) Adverse Events
	Bortezomib + Rituximab		Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	288/334 (86.2%)		232/339 (68.4%)
Blood and lymphatic system disorders
Thrombocytopenia	32/334 (9.6%)		13/339 (3.8%)
Gastrointestinal disorders
Abdominal pain upper	20/334 (6%)		7/339 (2.1%)
General disorders
Chills	28/334 (8.4%)		17/339 (5%)
Fatigue	75/334 (22.5%)		27/339 (8%)
Hepatobiliary disorders
Hepatic function abnormal	16/334 (4.8%)		11/339 (3.2%)
Infections and infestations
Nasopharyngitis	22/334 (6.6%)		8/339 (2.4%)
Musculoskeletal and connective tissue disorders
Back pain	37/334 (11.1%)		25/339 (7.4%)
Pain in extremity	46/334 (13.8%)		15/339 (4.4%)
Muscle spasms	16/334 (4.8%)		8/339 (2.4%)
Myalgia	18/334 (5.4%)		5/339 (1.5%)
Nervous system disorders
Headache	42/334 (12.6%)		24/339 (7.1%)
Paraesthesia	39/334 (11.7%)		10/339 (2.9%)
Dizziness	20/334 (6%)		9/339 (2.7%)
Neuralgia	23/334 (6.9%)		1/339 (0.3%)
Psychiatric disorders
Insomnia	30/334 (9%)		18/339 (5.3%)
Respiratory, thoracic and mediastinal disorders
Cough	51/334 (15.3%)		31/339 (9.1%)
Skin and subcutaneous tissue disorders
Pruritus	25/334 (7.5%)		15/339 (4.4%)
Rash	24/334 (7.2%)		10/339 (2.9%)
Vascular disorders
Hypertension	21/334 (6.3%)		9/339 (2.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.