S0601 Rituximab, Combination Chemotherapy, and Bortezomib Followed by Bortezomib Alone in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00376961
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 68
• Locations: 147
• Arm: 1
• Duration (Months): 133
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving rituximab together with combination chemotherapy and bortezomib may kill more cancer cells. Giving bortezomib as maintenance therapy may keep the cancer from progressing.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy and bortezomib followed by bortezomib alone works in treating patients with newly diagnosed mantle cell lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab; Drug: bortezomib; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the 2-year progression-free survival rate in patients with newly diagnosed mantle cell lymphoma treated with induction therapy comprising rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone, and bortezomib followed by bortezomib maintenance (VM) therapy.

Secondary

• Determine the response rate (complete, complete unconfirmed, and partial responses) in patients treated with this regimen.

• Determine the toxicity of VM in these patients.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive R-CHOP-V induction therapy comprising rituximab IV over ≤ 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin hydrochloride IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1; oral prednisone once daily on days 1-5; and bortezomib IV over 30-90 minutes on days 1 and 4. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable disease or better proceed to bortezomib maintenance therapy.

• Maintenance therapy: Beginning 3 months after completion of R-CHOP-V induction therapy, patients receive bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 3 months for up to 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 4 years and then annually for 3 years.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Combination Rituximab-CHOP and Bortezomib (Velcade®) (R-CHOP-V) Induction Therapy Followed by Bortezomib Maintenance (VM) Therapy for Patients With Newly Diagnosed Mantle Cell Lymphoma
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Sep 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: R-CHOP + Velcade 6 21-day cycles of standard R-CHOP with 1.3 mg/m^2 Bortezomib given on days 1 and 4 of each cycle. This is followed by 8 3-month cycles of maintenance with 1.3 mg/m^2 Bortezomib on days 1, 4, 8 and 11 of each cycle.

Biological: rituximab; 375 mg/m^2 on day 1 for cycles 1-6.; Other Names: Rituxan ; Drug: bortezomib; 1.3 mg/m^2 on days 1, 4 of cycles 1-6 and on days 1, 4, 8, 11 of cycles 7-14.; Other Names: Velcade ; Drug: cyclophosphamide; 750 mg/m^2 on day 1 of cycles 1-6.; Drug: doxorubicin hydrochloride; 50 mg/m^2 on day 1 of cycles 1-6.; Drug: prednisone; 100 mg on days 1-5 of cycles 1-6.; Drug: vincristine sulfate; 1.4 mg/m^2 on day 1 of cycles 1-6.

Outcome Measures

Primary Outcome Measures

1. 2-year Progression-free Survival in Patients Treated With Rituximab-CHOP-bortezomib Induction Therapy (RCHOP-V) Followed by Bortezomib Maintenance Therapy (VM) [0-2 years]

   Measured from date of registration to date of first observation of relapsed or progressive disease, or death due to any cause.

Secondary Outcome Measures

1. Response Rate in Patients Treated With Rituximab-CHOPbortezomib Induction Therapy (R-CHOP-V) Followed by Bortezomib Maintenance Therapy(VM). [At the time of restaging (between Cycles 6 and 7), every 6 months during Cycles 7-14, and at the end of protocol treatment]

   Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.

2. 2-year Overall Survival in Patients Treated With Rituximab-CHOP-bortezomib Induction Therapy (RCHOP-V) Followed by Bortezomib Maintenance Therapy (VM) [0-2 years]

   Measured from date of registration to date of death due to any cause or last contact

3. Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [Assessed prior to each cycle (for Cycles 2-6), at restaging (between Cycle 6 and 7), every 3 months ( for Cycle 7-14), and at the end of protocol treatment.]

   Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed mantle cell lymphoma (MCL) meeting the following criteria:

• Stage III-IV or bulky stage II disease

• Confirmation of positivity for the following phenotypes by immunohistochemistry or flow cytometry:

• Cluster of differentiation antigen 19 (CD19) (or CD20)

• Cyclin D1 OR evidence of t(11;14) translocation by cytogenetic analysis or fluorescent in situ hybridization

• Newly diagnosed, previously untreated disease

• Bidimensionally measurable disease by conventional techniques

• No nonmeasurable disease only

• Adequate tumor tissue from original diagnostic specimen available

• Tissue obtained by needle aspiration or cytology not allowed

• No clinical evidence of central nervous system (CNS) involvement by lymphoma

• Co-registration on protocols SWOG-8947 and SWOG-8819 is strongly encouraged

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No peripheral neuropathy ≥ grade 2

• No hypersensitivity to bortezomib, boron, or mannitol

• No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer for which the patient is currently in complete remission, or any other cancer for which the patient has been disease free for the past 5 years

• HIV negative

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, radiotherapy, or antibody therapy for lymphoma

• More than 14 days since prior investigational drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Regional Hospital Cancer Center	Anchorage	Alaska	United States	99508
2	Providence Cancer Center	Anchorage	Alaska	United States	99508
3	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724-5024
4	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
5	Providence Saint Joseph Medical Center - Burbank	Burbank	California	United States	91505
6	North Bay Cancer Center	Fairfield	California	United States	94533
7	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
8	Broward General Medical Center Cancer Center	Fort Lauderdale	Florida	United States	33316
9	M.D. Anderson Cancer Center at Orlando	Orlando	Florida	United States	32806
10	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho	United States	83712
11	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
12	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
13	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
14	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
15	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
16	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
17	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
18	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
19	Southwest Medical Center	Liberal	Kansas	United States	67901
20	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
21	Olathe Cancer Center	Olathe	Kansas	United States	66061
22	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
23	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
24	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
25	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas	United States	67401
26	Cotton-O'Neil Cancer Center	Topeka	Kansas	United States	66606
27	St. Francis Comprehensive Cancer Center	Topeka	Kansas	United States	66606
28	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
29	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67203
30	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
31	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
32	CCOP - Wichita	Wichita	Kansas	United States	67214
33	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
34	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
35	Boston University Cancer Research Center	Boston	Massachusetts	United States	02118
36	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
37	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
38	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
39	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
40	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
41	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
42	Metro Health Hospital	Grand Rapids	Michigan	United States	49506
43	Holland Community Hospital	Holland	Michigan	United States	49423
44	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan	United States	48910
45	Hackley Hospital	Muskegon	Michigan	United States	49442
46	Munson Medical Center	Traverse City	Michigan	United States	49684
47	University of Mississippi Cancer Clinic	Jackson	Mississippi	United States	39216
48	CCOP - Kansas City	Kansas City	Missouri	United States	64131
49	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
50	St. John's Regional Health Center	Springfield	Missouri	United States	65804
51	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
52	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
53	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
54	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
55	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
56	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
57	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
58	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
59	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
60	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
61	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
62		Great Falls	Montana	United States	59405
63	St. Peter's Hospital	Helena	Montana	United States	59601
64	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
65	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
66	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
67	Community Medical Center	Missoula	Montana	United States	59801
68	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
69	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
70	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
71	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska	United States	68848-1990
72	Adirondack Cancer Care - Glens Falls	Glens Falls	New York	United States	12801
73	Tucker Center for Cancer Care at Orange Regional Medical Center	Middletown	New York	United States	10940-4199
74	Interlakes Oncology/Hematology PC	Rochester	New York	United States	14623
75	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
76	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
77	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
78	Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
79	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
80	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
81	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
82	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
83	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
84	CCOP - Columbus	Columbus	Ohio	United States	43215
85	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
86	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
87	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
88	Grandview Hospital	Dayton	Ohio	United States	45405
89	Good Samaritan Hospital	Dayton	Ohio	United States	45406
90	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
91	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
92	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
93	CCOP - Dayton	Dayton	Ohio	United States	45429
94	Grady Memorial Hospital	Delaware	Ohio	United States	43015
95	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
96	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
97	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
98	Fairfield Medical Center	Lancaster	Ohio	United States	43130
99	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
100	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
101	Mercy Medical Center	Springfield	Ohio	United States	45504
102	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
103	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
104	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
105	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
106	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
107	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
108	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
109	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon	United States	97210
110	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
111	Adventist Medical Center	Portland	Oregon	United States	97216
112	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
113	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
114	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon	United States	97227
115	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
116	AnMed Cancer Center	Anderson	South Carolina	United States	29621
117	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
118	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
119	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
120	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee	United States	37662
121	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
122	American Fork Hospital	American Fork	Utah	United States	84003
123	Sandra L. Maxwell Cancer Center	Cedar City	Utah	United States	84720
124	Logan Regional Hospital	Logan	Utah	United States	84321
125	Cottonwood Hospital Medical Center	Murray	Utah	United States	84107
126	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
127	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah	United States	84403
128	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
129	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
130	LDS Hospital	Salt Lake City	Utah	United States	84103
131	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah	United States	84106
132	Danville Regional Medical Center	Danville	Virginia	United States	24541
133	Southwest Virginia Regional Cancer Center at Wellmonth Health	Norton	Virginia	United States	24273
134	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
135	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
136	Columbia Basin Hematology	Kennewick	Washington	United States	99336
137	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98104
138	Harborview Medical Center	Seattle	Washington	United States	98104
139	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
140	Group Health Central Hospital	Seattle	Washington	United States	98112
141	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
142	Polyclinic First Hill	Seattle	Washington	United States	98122
143	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043
144	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
145	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
146	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028
147	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Steven H. Bernstein, MD, James P. Wilmot Cancer Center
• Study Chair: Richard I. Fisher, MD, James P. Wilmot Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00376961
• Other Study ID Numbers: CDR0000494646; U10CA032102; S0601
• First Posted: Sep 15, 2006
• Last Update Posted: Nov 6, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by Southwest Oncology Group: contiguous stage II mantle cell lymphoma; noncontiguous stage II mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Mantle-Cell; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Vincristine; Bortezomib

Study Results

Participant Flow

Arm/Group Title	Rituximab-CHOP-Bortezomib (R-CHOP-V) Induction	Bortezomib Maintenance (VM)
Arm/Group Description	Rituximab-CHOP-Bortezomib (R-CHOP-V) induction is administered every 21 days for 6 cycles (1 cycle = 21 days)	Bortezomib maintenance (VM) therapy is given 3 months after the completion of R-CHOP-V induction therapy. Treatment with VM is administered once every 3 month for 8 cycles, Cycle 7-14 ( 1 cycle = 3 months)
Period Title: Initial Registration
STARTED	68	0
Eligible	65	0
COMPLETED	61	0
NOT COMPLETED	7	0
Period Title: Initial Registration
STARTED	0	50
Eligible	0	47
COMPLETED	0	27
NOT COMPLETED	0	23

Baseline Characteristics

Arm/Group Title	Rituximab-CHOP-Bortezomib (R-CHOP-V)
Arm/Group Description	R-CHOP-V will be administered for 6 cycles (one cycle is defined as a single 21-day course of treatment).
Overall Participants	65
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	13 20%
Male	52 80%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.5%
Not Hispanic or Latino	51 78.5%
Unknown or Not Reported	13 20%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 1.5%
Native Hawaiian or Other Pacific Islander	1 1.5%
Black or African American	2 3.1%
White	61 93.8%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Secondary Outcome

Title	Response Rate in Patients Treated With Rituximab-CHOPbortezomib Induction Therapy (R-CHOP-V) Followed by Bortezomib Maintenance Therapy(VM).
Description	Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.
Time Frame	At the time of restaging (between Cycles 6 and 7), every 6 months during Cycles 7-14, and at the end of protocol treatment

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in the analysis.

Arm/Group Title	R-CHOP-V Followed by VM
Arm/Group Description	Rituximab-CHOP-bortezomib induction therapy (RCHOP-V) followed by Bortezomib maintenance therapy (VM). R-CHOP-V is administered for 6 cycles (1 cycle = 21 days). Bortezomib maintenance (VM) therapy is given 3 months after the completion of R-CHOP-V induction therapy. Treatment with VM is administered once every 3 month for 8 cycles, Cycle 7-14 ( 1 cycle = 3 months)
Measure Participants	65
Complete Response	17 26.2%
Partial Response	16 24.6%
Unconfirmed Complete Response	13 20%
Unconfirmed Partial Response	1 1.5%
No Response	4 6.2%
Assessment Inadequate	14 21.5%

2. Primary Outcome

Title	2-year Progression-free Survival in Patients Treated With Rituximab-CHOP-bortezomib Induction Therapy (RCHOP-V) Followed by Bortezomib Maintenance Therapy (VM)
Description	Measured from date of registration to date of first observation of relapsed or progressive disease, or death due to any cause.
Time Frame	0-2 years

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in the analysis

Arm/Group Title	R-CHOP-V Followed by VM
Arm/Group Description	Rituximab-CHOP-bortezomib induction therapy (RCHOP-V) followed by Bortezomib maintenance therapy (VM). R-CHOP-V is administered for 6 cycles (1 cycle = 21 days). Bortezomib maintenance (VM) therapy is given 3 months after the completion of R-CHOP-V induction therapy. Treatment with VM is administered once every 3 month for 8 cycles, Cycle 7-14 ( 1 cycle = 3 months)
Measure Participants	65
Number (95% Confidence Interval) [percentage of participants]	62 95.4%

3. Secondary Outcome

Title	2-year Overall Survival in Patients Treated With Rituximab-CHOP-bortezomib Induction Therapy (RCHOP-V) Followed by Bortezomib Maintenance Therapy (VM)
Description	Measured from date of registration to date of death due to any cause or last contact
Time Frame	0-2 years

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in the analysis.

Arm/Group Title	R-CHOP-V Followed by VM
Arm/Group Description	Rituximab-CHOP-bortezomib induction therapy (RCHOP-V) followed by Bortezomib maintenance therapy (VM). R-CHOP-V is administered for 6 cycles (1 cycle = 21 dyas). Bortezomib maintenance (VM) therapy is given 3 months after the completion of R-CHOP-V induction therapy. Treatment with VM is administered once every 3 month for 8 cycles, Cycle 7-14 ( 1 cycle = 3 months)
Measure Participants	65
Number (95% Confidence Interval) [percentage of participants]	85 130.8%

4. Secondary Outcome

Title	Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Description	Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Time Frame	Assessed prior to each cycle (for Cycles 2-6), at restaging (between Cycle 6 and 7), every 3 months ( for Cycle 7-14), and at the end of protocol treatment.

Outcome Measure Data

Analysis Population Description

Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which deemed to be related to protocol treatment are included.

Arm/Group Title	Rituximab-CHOP-Bortezomib (R-CHOP-V) Induction	Bortezomib Maintenance (VM)
Arm/Group Description	Rituximab-CHOP-Bortezomib (R-CHOP-V) induction is administered every 21 days for 6 cycles (1 cycle = 21 days)	Bortezomib maintenance (VM) therapy is given 3 months after the completion of R-CHOP-V induction therapy. Treatment with VM is administered once every 3 month for 8 cycles, Cycle 7-14 ( 1 cycle = 3 months)
Measure Participants	65	47
Albumin, serum-low (hypoalbuminemia)	1 1.5%	0 NaN
Anorexia	1 1.5%	0 NaN
Calcium, serum-low (hypocalcemia)	1 1.5%	0 NaN
Constipation	1 1.5%	0 NaN
Dehydration	1 1.5%	0 NaN
Diarrhea	3 4.6%	0 NaN
Dizziness	1 1.5%	0 NaN
Dyspnea (shortness of breath)	1 1.5%	1 NaN
Edema: limb	1 1.5%	0 NaN
Fatigue (asthenia, lethargy, malaise)	6 9.2%	1 NaN
Febrile neutropenia	12 18.5%	0 NaN
GGT (gamma-glutamyl transpeptidase)	1 1.5%	1 NaN
Glucose, serum-high (hyperglycemia)	3 4.6%	0 NaN
Hemoglobin	3 4.6%	0 NaN
Hypoxia	1 1.5%	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	3 4.6%	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - Oral cav-gums	1 1.5%	0 NaN
Inf (clin/microbio) w/Gr 3-4 neuts - Sinus	1 1.5%	0 NaN
Inf w/normal ANC or Gr 1-2 neutrophils - Ext ear	1 1.5%	0 NaN
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	1 1.5%	0 NaN
Inf w/normal ANC or Gr 1-2 neutrophils - Oral cav	1 1.5%	0 NaN
Inf w/normal ANC or Gr 1-2 neutrophils - Sinus	0 0%	1 NaN
Inf w/normal ANC or Gr 1-2 neutrophils -Nerve-peri	1 1.5%	0 NaN
Infection-Other (Specify)	1 1.5%	0 NaN
Leukocytes (total WBC)	26 40%	0 NaN
Lymphopenia	15 23.1%	2 NaN
Mucositis/stomatitis (functional/symp) - Oral cav	1 1.5%	0 NaN
Muscle weakness, not d/t neuropathy - body/general	1 1.5%	0 NaN
Nausea	2 3.1%	0 NaN
Neuropathy: CN V Motor-jaw muscles; Sensory-facial	1 1.5%	0 NaN
Neuropathy: motor	2 3.1%	0 NaN
Neuropathy: sensory	2 3.1%	1 NaN
Neutrophils/granulocytes (ANC/AGC)	34 52.3%	0 NaN
Pain - Head/headache	0 0%	1 NaN
Phosphate, serum-low (hypophosphatemia)	1 1.5%	0 NaN
Platelets	11 16.9%	0 NaN
Pneumonitis/pulmonary infiltrates	1 1.5%	0 NaN
Potassium, serum-low (hypokalemia)	2 3.1%	0 NaN
Pruritus/itching	1 1.5%	0 NaN
Renal failure	1 1.5%	0 NaN
Syncope (fainting)	2 3.1%	0 NaN
Thrombosis/embolism (vascular access-related)	1 1.5%	0 NaN
Thrombosis/thrombus/embolism	1 1.5%	0 NaN
Uric acid, serum-high (hyperuricemia)	1 1.5%	0 NaN
Urticaria (hives, welts, wheals)	0 0%	1 NaN

Adverse Events

Time Frame	Assessed prior to each cycle (for Cycles 2-6), at restaging (between Cycle 6 and 7), every 3 months ( for Cycle 7-14), and at the end of protocol treatment.
Arm/Group Title	Rituximab-CHOP-Bortezomib (R-CHOP-V) Induction		Bortezomib Maintenance (VM)
Arm/Group Description	Rituximab-CHOP-Bortezomib (R-CHOP-V) induction is administered every 21 days for 6 cycles (1 cycle= 21 days)		Bortezomib maintenance (VM) therapy is given 3 months after the completion of R-CHOP-V induction therapy. Treatment with VM is administered once every 3 month for 8 cycles, Cycle 7-14 ( 1 cycle = 3 months)
All Cause Mortality
	Rituximab-CHOP-Bortezomib (R-CHOP-V) Induction		Bortezomib Maintenance (VM)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rituximab-CHOP-Bortezomib (R-CHOP-V) Induction		Bortezomib Maintenance (VM)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/65 (1.5%)		0/47 (0%)
General disorders
Sudden death	1/65 (1.5%)		0/47 (0%)
Other (Not Including Serious) Adverse Events
	Rituximab-CHOP-Bortezomib (R-CHOP-V) Induction		Bortezomib Maintenance (VM)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/65 (98.5%)		43/47 (91.5%)
Blood and lymphatic system disorders
Febrile neutropenia	12/65 (18.5%)		0/47 (0%)
Hemoglobin	47/65 (72.3%)		15/47 (31.9%)
Ear and labyrinth disorders
Auditory/Ear-Other (Specify)	0/65 (0%)		3/47 (6.4%)
Eye disorders
Vision-blurred vision	9/65 (13.8%)		0/47 (0%)
Watery eye (epiphora, tearing)	6/65 (9.2%)		0/47 (0%)
Gastrointestinal disorders
Constipation	32/65 (49.2%)		8/47 (17%)
Diarrhea	15/65 (23.1%)		7/47 (14.9%)
Dry mouth/salivary gland (xerostomia)	4/65 (6.2%)		0/47 (0%)
Heartburn/dyspepsia	12/65 (18.5%)		3/47 (6.4%)
Mucositis/stomatitis (clinical exam) - Oral cavity	4/65 (6.2%)		0/47 (0%)
Mucositis/stomatitis (functional/symp) - Oral cav	10/65 (15.4%)		0/47 (0%)
Nausea	35/65 (53.8%)		9/47 (19.1%)
Pain - Abdomen NOS	11/65 (16.9%)		5/47 (10.6%)
Vomiting	12/65 (18.5%)		0/47 (0%)
General disorders
Edema: limb	13/65 (20%)		3/47 (6.4%)
Fatigue (asthenia, lethargy, malaise)	52/65 (80%)		24/47 (51.1%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	7/65 (10.8%)		0/47 (0%)
Pain-Other (Specify)	0/65 (0%)		3/47 (6.4%)
Rigors/chills	11/65 (16.9%)		3/47 (6.4%)
Immune system disorders
Allergic reaction/hypersensitivity	6/65 (9.2%)		0/47 (0%)
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	0/65 (0%)		3/47 (6.4%)
Inf w/normal ANC or Gr 1-2 neutrophils - Sinus	4/65 (6.2%)		3/47 (6.4%)
Inf w/normal ANC or Gr 1-2 neutrophils - Up airway	0/65 (0%)		8/47 (17%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	6/65 (9.2%)		3/47 (6.4%)
AST, SGOT	6/65 (9.2%)		0/47 (0%)
Alkaline phosphatase	7/65 (10.8%)		3/47 (6.4%)
Bilirubin (hyperbilirubinemia)	0/65 (0%)		5/47 (10.6%)
Creatinine	8/65 (12.3%)		7/47 (14.9%)
Leukocytes (total WBC)	45/65 (69.2%)		15/47 (31.9%)
Lymphopenia	27/65 (41.5%)		12/47 (25.5%)
Metabolic/Laboratory-Other (Specify)	10/65 (15.4%)		0/47 (0%)
Neutrophils/granulocytes (ANC/AGC)	40/65 (61.5%)		3/47 (6.4%)
Platelets	27/65 (41.5%)		19/47 (40.4%)
Weight gain	0/65 (0%)		5/47 (10.6%)
Weight loss	10/65 (15.4%)		0/47 (0%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	10/65 (15.4%)		0/47 (0%)
Anorexia	17/65 (26.2%)		5/47 (10.6%)
Calcium, serum-low (hypocalcemia)	11/65 (16.9%)		5/47 (10.6%)
Dehydration	5/65 (7.7%)		0/47 (0%)
Glucose, serum-high (hyperglycemia)	29/65 (44.6%)		21/47 (44.7%)
Glucose, serum-low (hypoglycemia)	4/65 (6.2%)		0/47 (0%)
Potassium, serum-low (hypokalemia)	6/65 (9.2%)		0/47 (0%)
Sodium, serum-low (hyponatremia)	9/65 (13.8%)		3/47 (6.4%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general	5/65 (7.7%)		0/47 (0%)
Pain - Back	6/65 (9.2%)		3/47 (6.4%)
Pain - Bone	4/65 (6.2%)		0/47 (0%)
Pain - Joint	15/65 (23.1%)		11/47 (23.4%)
Pain - Muscle	14/65 (21.5%)		8/47 (17%)
Nervous system disorders
Dizziness	9/65 (13.8%)		3/47 (6.4%)
Neuropathy: motor	4/65 (6.2%)		0/47 (0%)
Neuropathy: sensory	39/65 (60%)		34/47 (72.3%)
Pain - Head/headache	6/65 (9.2%)		8/47 (17%)
Taste alteration (dysgeusia)	14/65 (21.5%)		4/47 (8.5%)
Psychiatric disorders
Insomnia	18/65 (27.7%)		6/47 (12.8%)
Mood alteration - anxiety	6/65 (9.2%)		4/47 (8.5%)
Mood alteration - depression	6/65 (9.2%)		0/47 (0%)
Renal and urinary disorders
Urinary frequency/urgency	10/65 (15.4%)		4/47 (8.5%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	7/65 (10.8%)		4/47 (8.5%)
Cough	14/65 (21.5%)		13/47 (27.7%)
Dyspnea (shortness of breath)	11/65 (16.9%)		9/47 (19.1%)
Hiccoughs (hiccups, singultus)	4/65 (6.2%)		0/47 (0%)
Skin and subcutaneous tissue disorders
Dry skin	4/65 (6.2%)		5/47 (10.6%)
Hair loss/Alopecia (scalp or body)	38/65 (58.5%)		0/47 (0%)
Pruritus/itching	0/65 (0%)		5/47 (10.6%)
Rash/desquamation	6/65 (9.2%)		7/47 (14.9%)
Rash: acne/acneiform	0/65 (0%)		4/47 (8.5%)
Sweating (diaphoresis)	7/65 (10.8%)		4/47 (8.5%)
Urticaria (hives, welts, wheals)	0/65 (0%)		3/47 (6.4%)
Vascular disorders
Flushing	5/65 (7.7%)		0/47 (0%)
Hypertension	4/65 (6.2%)		3/47 (6.4%)
Hypotension	5/65 (7.7%)		0/47 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.