Study of Bendamustine Hydrochloride and Rituximab (BR) Compared With R-CVP or R-CHOP in the First-Line Treatment of Patients With Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell Lymphoma (MCL) - Referred to as the BRIGHT Study
Study Details
Study Description
Brief Summary
The primary objective of the study is to compare the complete response (CR) rate of bendamustine and rituximab (BR) with that of standard treatment regimens of either rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with advanced, indolent non-Hodgkin's lymphoma (NHL) or mantle cell lymphoma (MCL).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Bendamustine and Rituximab (BR) Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1 |
Drug: bendamustine
Other Names:
Drug: rituximab
Other Names:
|
Active Comparator: R-CHOP/R-CVP Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Drug: rituximab
Other Names:
Drug: vincristine
Other Names:
Drug: prednisone
Drug: cyclophosphamide
Other Names:
Drug: doxorubicin
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Complete Response (CR) at End of Treatment Period [6 to 8 21 or 28-day cycles (18-32 weeks)]
CR=complete disappearance of all detectable clinical evidence of disease and disease-related symptoms, if present pretherapy; protocol-specified positron emission tomography (PET) scan assessment criteria; (if the spleen and/or liver were enlarged on the basis of physical examination and/or anatomic imaging before treatment) the liver and/or spleen were considered normal size on physical examination and by anatomic imaging after therapy, with disappearance of all nodules related to lymphoma; (if the bone marrow was involved by lymphoma before treatment) the infiltrate must have cleared on subsequent bone marrow biopsies.
Secondary Outcome Measures
- Percentage of Participants With Overall Response at End of Treatment Period [6 to 8 21 or 28-day cycles (18-32 weeks)]
Overall Response=participants with Complete Remission (CR) + those with Partial Remission (PR). CR=see Outcome Measure 1 for details. PR= at least a 50% decrease in the sum of the product of the greatest diameters (SPD) of up to 6 of the largest dominant nodes/masses; at least a 50% decrease in the SPD of hepatic and splenic nodules in their greatest transverse diameter; no increase in the size of the liver, spleen, and other nodes; no measurable disease in organs other than the liver or spleen; no new sites of disease; protocol-specified PET scan and bone marrow criteria.
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period [32 weeks]
AE=any untoward medical occurrence that develops or worsens in severity after dispensation of the study drug and does not necessarily have a causal relationship to the study drug. An AE can, therefore, be any unfavorable and unintended physical sign, symptom, or laboratory parameter that develops or worsens in severity during the course of the study, or significant worsening of the disease under study (or any concurrent disease), whether or not considered related to the study drug. AEs were graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). SAE=an adverse event occurring at any dose that results in: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity (a substantial disruption of one's ability to conduct normal life functions), a congenital anomaly/birth defect, or other important medical event.
- Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results [32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)]
Clinical laboratory data were graded according to National Cancer Institute's (NCI) CTCAE version 3, and graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). The table presents the worst CTCAE grades for serum chemistry test results experienced by participants overall (i.e., the worst post-baseline grade value for each participant and laboratory test across all cycles).
- Worst Overall CTCAE Grade for Hematology Laboratory Test Results [32 weeks (conducted at screening, Day 1 of each cycle, weekly during treatment, and at the end-of-treatment visit)]
Hematology test data were graded according to National Cancer Institute's (NCI) CTCAE version 3, and graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). The table presents the worst CTCAE grades for hematology test results experienced by participants overall (i.e., the worst post-baseline grade value for each participant and hematology test across all cycles).
- Clinically Significant Abnormal Vital Signs [32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit)]
- Potentially Clinically Significant Abnormal Weight [Baseline, Week 32]
Participants were weighed at Baseline and at Endpoint (Week 32); those participants with an increase or decrease of >=10% were considered potentially clinically significant.
- Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period [Week 32]
Participants' ECOG Performance Status was evaluated at the end of treatment as improved, stayed the same, or worsened from baseline (see Baseline Characteristics for ECOG Performance Status).
- Therapeutic Classification of Prior Medications [prior to start of treatment]
- Therapeutic Classification of Concomitant Medications [32 weeks]
- Change From Baseline to End of Treatment in the Global Health Status Score of the European Organization for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire (QLQ-C30) [Day 1 (prior to treatment), 32 weeks]
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). This outcome reports the global health status on a scale of 0-100 with a high score for the global health status/QOL represents a high quality of life.
- Participants With Disease Progression, Relapse or Death At the End of the Treatment Period or the Long-Term Follow-up Period [Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period]
Relapsed disease (after CR) and progressive disease (PD) (after PR or SD): Lymph nodes were considered abnormal if the long axis was greater than 1.5 cm. Lymph nodes with a long axis of 1.1 to 1.5 cm were considered abnormal if its short axis was greater than 1.0 cm. In patients with no prior history of pulmonary lymphoma, new lung nodules identified by CT require histologic confirmation. >= 50% increase from nadir in sum of the products of the greatest diameters (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions (eg, splenic or hepatic nodules). To be considered progressive disease, a lymph node with a diameter of the short axis of less than 1.0 cm must have increased by 2: 50% and to a size of 1.5 cm by 1.5 cm, or more than 1.5 cm in the long axis other conditions as specified in the protocol
- Kaplan-Meier Estimate for Progression-free Survival (PFS) [Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)]
PFS was defined as the time from randomization to disease progression or relapse, or death from any cause, whichever occurred first.
- Kaplan-Meier Estimate for Event-free Survival (EFS) [Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)]
EFS was defined as the time from randomization to treatment failure, disease progression or relapse, other malignancies, or death from any cause, whichever occurred first. Treatment failure was defined as failure to achieve a CR or PR after 6 cycles of treatment. If a patient failed to achieve CR or PR by the time of data analysis or early withdrawal, the treatment failure date was set at 126 days (6 cycles of treatment) after randomization or the new anticancer treatment date, whichever is earlier.
- Kaplan-Meier Estimate for Duration of Response (DOR) [Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)]
DOR was defined as the time from first response (CR or PR) to disease progression or relapse, or death due to any cause.
- Overall Survival (OS) [Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period)]
OS was defined as the time from randomization to death from any cause.
- Participants Who Died At the End of the Treatment Period or the Long-Term Follow-up Period [Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period]
Death is due to any cause. Data are broken out by patients who died within 30 days of the last dose of study medications, and those who died greater than 30 days of the last dose of study medications.
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Histopathologic confirmation of one of the following cluster of differentiation antigen 20 positive (CD20+) B-cell non-Hodgkin's lymphomas (tissue diagnostic procedures must be performed within 6 months of study entry and with biopsy material available for review):
-
follicular lymphoma (NCI CTCAE grade 1 or 2)
-
immunoplasmacytoma/immunocytoma (Waldenstrom's macroglobulinemia)
-
splenic marginal zone B-cell lymphoma
-
extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tumor (MALT) type
-
nodal marginal zone B-cell lymphoma
-
mantle cell lymphoma
-
Meets one of the following need-for-treatment criteria (with the exception of mantle cell lymphoma for which treatment is indicated):
-
presence of at least one of the following B-symptoms:
-
fever (>38ºC) of unclear etiology
-
night sweats
-
weight loss of greater than 10% within the prior 6 months
-
large tumor mass (bulky disease)
-
presence of lymphoma-related complications, including narrowing of ureters or bile ducts, tumor-related compression of a vital organ, lymphoma-induced pain, cytopenias related to lymphoma/leukemia, splenomegaly, pleural effusions, or ascites
-
hyperviscosity syndrome due to monoclonal gammopathy
-
CD20+ B cells in lymph node biopsy or other lymphoma pathology specimen.
-
No prior treatment (patients on "watch and wait" may enter the study if a recent biopsy [obtained within the last 6 months] is available)
-
Adequate hematologic function (unless abnormalities related to lymphoma infiltration of the bone marrow or hypersplenism due to lymphoma) as follows:
-
hemoglobin of >= 10.0 g/dL
-
absolute neutrophil count (ANC) >=1.5*10^9/L
-
platelet count >=100*10^9/L
-
Bidimensionally measurable disease (field not previously radiated)
-
Able to provide written informed consent
-
Eastern Cooperative Oncology Group (ECOG) Performance Status <=2
-
Estimated life expectancy >=6 months
-
Serum creatinine of <=2.0 mg/dL or creatinine clearance >=50 mL/min
-
Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤2.5*upper limit of normal (ULN), and alkaline phosphatase and total bilirubin within normal limits
-
Left ventricular ejection fraction (LVEF) >= 50% by multiple gated acquisition scan (MUGA) or cardiac echocardiogram (ECHO), prior for any patient to be treated with R-CHOP
-
A medically accepted method of contraception to be used by women of childbearing potential (not surgically sterile or at least 12 months naturally postmenopausal)
-
Men capable of producing offspring and not surgically sterile must practice abstinence or use a barrier method of birth control.
Key Exclusion Criteria:
-
Chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL), or grade 3 follicular lymphoma
-
Transformed disease (bone marrow blasts are permitted; however, transformed disease indicating leukemic involvement is not permitted)
-
Central nervous system (CNS) lymphomatous involvement or leptomeningeal lymphoma
-
Prior radiation for NHL, except for a single course of locally delimited radiation therapy with a radiation field not exceeding 2 adjacent lymph node regions
-
Active malignancy, other than NHL, within the past 3 years except for localized prostate cancer treated with hormone therapy, cervical carcinoma in situ, breast cancer in situ, or non-melanoma skin cancer following definitive treatment
-
New York Heart Association (NYHA) Class III or IV heart failure, arrhythmias or unstable angina, electrocardiograph (ECG) evidence of active ischemia or active conduction system abnormalities, or myocardial infarction within the last 6 months (prior to study entry, ECG abnormalities at screening must be documented by the investigator as not medically relevant)
-
Known human immunodeficiency virus (HIV) positivity
-
Active hepatitis B or hepatitis C infection (hepatitis B surface antigen testing required)
-
Women who are pregnant or lactating
-
Corticosteroids for treatment of lymphoma within 28 days of study entry Chronically administered low-dose corticosteroids (e.g., prednisone ≤20 mg/day) for indications other than lymphoma or lymphoma-related complications are permitted
-
Any serious uncontrolled, medical or psychological disorder that would impair the ability of the patient to receive therapy
-
Any condition which places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data
-
Any other investigational agent within 28 days of study entry
-
Known hypersensitivity to bendamustine, mannitol, or other study-related drugs
-
Ann Arbor stage I disease.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Teva Investigational Site 165 | Tucson | Arizona | United States | |
2 | Teva Investigational Site 167 | Little Rock | Arkansas | United States | |
3 | Teva Investigational Site 11 | Corona | California | United States | |
4 | Teva Investigational Site 21 | Fountain Valley | California | United States | |
5 | Teva Investigational Site 52 | Fountain Valley | California | United States | |
6 | Teva Investigational Site 64 | Fullerton | California | United States | |
7 | Teva Investigational Site 40 | Los Angeles | California | United States | |
8 | Teva Investigational Site 53 | Los Angeles | California | United States | |
9 | Teva Investigational Site 57 | San Diego | California | United States | |
10 | Teva Investigational Site 15 | Aurora | Colorado | United States | |
11 | Teva Investigational Site 155 | Denver | Colorado | United States | |
12 | Teva Investigational Site 5 | Fort Collins | Colorado | United States | |
13 | Teva Investigational Site 70 | New Britain | Connecticut | United States | |
14 | Teva Investigational Site 37 | Norwalk | Connecticut | United States | |
15 | Teva Investigational Site 67 | Southington | Connecticut | United States | |
16 | Teva Investigational Site 58 | Fort Myers | Florida | United States | |
17 | Teva Investigational Site 38 | Hollywood | Florida | United States | |
18 | Teva Investigational Site 23 | Jacksonville | Florida | United States | |
19 | Teva Investigational Site 65 | Lake Worth | Florida | United States | |
20 | Teva Investigational Site 156 | Miami | Florida | United States | |
21 | Teva Investigational Site 160 | Orlando | Florida | United States | |
22 | Teva Investigational Site 68 | Orlando | Florida | United States | |
23 | Teva Investigational Site 72 | Augusta | Georgia | United States | |
24 | Teva Investigational Site 50 | Columbus | Georgia | United States | |
25 | Teva Investigational Site 73 | Macon | Georgia | United States | |
26 | Teva Investigational Site 49 | Centralia | Illinois | United States | |
27 | Teva Investigational Site 48 | Chicago | Illinois | United States | |
28 | Teva Investigational Site 9 | Chicago | Illinois | United States | |
29 | Teva Investigational Site 14 | Normal | Illinois | United States | |
30 | Teva Investigational Site 24 | Beech Grove | Indiana | United States | |
31 | Teva Investigational Site 152 | Indianapolis | Indiana | United States | |
32 | Teva Investigational Site 31 | Iowa City | Iowa | United States | |
33 | Teva Investigational Site 63 | Waterloo | Iowa | United States | |
34 | Teva Investigational Site 47 | Wichita | Kansas | United States | |
35 | Teva Investigational Site 33 | Lexington | Kentucky | United States | |
36 | Teva Investigational Site 19 | Shreveport | Louisiana | United States | |
37 | Teva Investigational Site 43 | Augusta | Maine | United States | |
38 | Teva Investigational Site 74 | Lowell | Massachusetts | United States | |
39 | Teva Investigational Site 22 | Duluth | Minnesota | United States | |
40 | Teva Investigational Site 4 | Saint Louis Park | Minnesota | United States | |
41 | Teva Investigational Site 162 | Columbia | Missouri | United States | |
42 | Teva Investigational Site 157 | Kansas City | Missouri | United States | |
43 | Teva Investigational Site 29 | Morristown | New Jersey | United States | |
44 | Teva Investigational Site 46 | Albuquerque | New Mexico | United States | |
45 | Teva Investigational Site 8 | Rochester | New York | United States | |
46 | Teva Investigational Site 10 | Syracuse | New York | United States | |
47 | Teva Investigational Site 17 | Charlotte | North Carolina | United States | |
48 | Teva Investigational Site 151 | Durham | North Carolina | United States | |
49 | Teva Investigational Site 39 | Fargo | North Dakota | United States | |
50 | Teva Investigational Site 34 | Cincinnati | Ohio | United States | |
51 | Teva Investigational Site 60 | Cincinnati | Ohio | United States | |
52 | Teva Investigational Site 28 | Cleveland | Ohio | United States | |
53 | Teva Investigational Site 153 | Springfield | Oregon | United States | |
54 | Teva Investigational Site 59 | Bethlehem | Pennsylvania | United States | |
55 | Teva Investigational Site 44 | Danville | Pennsylvania | United States | |
56 | Teva Investigational Site 3 | Philadelphia | Pennsylvania | United States | |
57 | Teva Investigational Site 13 | Pittsburgh | Pennsylvania | United States | |
58 | Teva Investigational Site 7 | Pottstown | Pennsylvania | United States | |
59 | Teva Investigational Site 25 | Charleston | South Carolina | United States | |
60 | Teva Investigational Site 71 | Columbia | South Carolina | United States | |
61 | Teva Investigational Site 56 | Chattanooga | Tennessee | United States | |
62 | Teva Investigational Site 30 | Nashville | Tennessee | United States | |
63 | Teva Investigational Site 154 | Arlington | Texas | United States | |
64 | Teva Investigational Site 158 | Arlington | Texas | United States | |
65 | Teva Investigational Site 6 | El Paso | Texas | United States | |
66 | Teva Investigational Site 161 | Fort Worth | Texas | United States | |
67 | Teva Investigational Site 159 | San Antonio | Texas | United States | |
68 | Teva Investigational Site 166 | Sugar Land | Texas | United States | |
69 | Teva Investigational Site 2 | Salt Lake City | Utah | United States | |
70 | Teva Investigational Site 18 | Abingdon | Virginia | United States | |
71 | Teva Investigational Site 35 | Charlottesville | Virginia | United States | |
72 | Teva Investigational Site 164 | Norfolk | Virginia | United States | |
73 | Teva Investigational Site 54 | Richmond | Virginia | United States | |
74 | Teva Investigational Site 42 | Seattle | Washington | United States | |
75 | Teva Investigational Site 150 | Spokane | Washington | United States | |
76 | Teva Investigational Site 163 | Vancouver | Washington | United States | |
77 | Teva Investigational Site 66 | Morgantown | West Virginia | United States | |
78 | Teva Investigational Site 41 | Madison | Wisconsin | United States | |
79 | Teva Investigational Site 62 | Wausau | Wisconsin | United States | |
80 | Teva Investigational Site 315 | Perth | Western Australia | Australia | |
81 | Teva Investigational Site 305 | Concord | Australia | ||
82 | Teva Investigational Site 317 | Douglas | Australia | ||
83 | Teva Investigational Site 308 | East Melbourne | Australia | ||
84 | Teva Investigational Site 310 | Fitzroy | Australia | ||
85 | Teva Investigational Site 311 | Fitzroy | Australia | ||
86 | Teva Investigational Site 301 | Garran | Australia | ||
87 | Teva Investigational Site 316 | Geelong | Australia | ||
88 | Teva Investigational Site 304 | Hobart | Australia | ||
89 | Teva Investigational Site 312 | Kurralta Park | Australia | ||
90 | Teva Investigational Site 307 | Melbourne | Australia | ||
91 | Teva Investigational Site 318 | Parkville | Australia | ||
92 | Teva Investigational Site 300 | South Brisbane | Australia | ||
93 | Teva Investigational Site 303 | Westmead | Australia | ||
94 | Teva Investigational Site 314 | Wodonga | Australia | ||
95 | Teva Investigational Site 313 | Woodville | Australia | ||
96 | Teva Investigational Site 309 | Woolloongabba | Australia | ||
97 | Teva Investigational Site 503 | Barretos | Brazil | ||
98 | Teva Investigational Site 504 | Brasilia | Brazil | ||
99 | Teva Investigational Site 506 | Curitiba | Brazil | ||
100 | Teva Investigational Site 505 | Goiânia | Brazil | ||
101 | Teva Investigational Site 502 | Jau | Brazil | ||
102 | Teva Investigational Site 509 | Lajeado | Brazil | ||
103 | Teva Investigational Site 507 | Porto Alegre | Brazil | ||
104 | Teva Investigational Site 508 | Porto Alegre | Brazil | ||
105 | Teva Investigational Site 511 | Rio De Janeiro | Brazil | ||
106 | Teva Investigational Site 500 | Santo Andre | Brazil | ||
107 | Teva Investigational Site 501 | Sao Paulo | Brazil | ||
108 | Teva Investigational Site 202 | Barrie | Canada | ||
109 | Teva Investigational Site 206 | Calgary | Canada | ||
110 | Teva Investigational Site 200 | Halifax | Canada | ||
111 | Teva Investigational Site 201 | Ottawa | Canada | ||
112 | Teva Investigational Site 203 | Vancouver | Canada | ||
113 | Teva Investigational Site 204 | Winnipeg | Canada | ||
114 | Teva Investigational Site 602 | Aguascalientes | Mexico | ||
115 | Teva Investigational Site 603 | Hermosillo | Mexico | ||
116 | Teva Investigational Site 600 | Monterrey | Mexico | ||
117 | Teva Investigational Site 601 | Monterrey | Mexico | ||
118 | Teva Investigational Site 401 | Auckland | New Zealand | ||
119 | Teva Investigational Site 405 | Auckland | New Zealand | ||
120 | Teva Investigational Site 400 | Christchurch | New Zealand | ||
121 | Teva Investigational Site 402 | Newtown | New Zealand | ||
122 | Teva Investigational Site 404 | Palmerston North | New Zealand | ||
123 | Teva Investigational Site 403 | Takapuna | New Zealand | ||
124 | Teva Investigational Site 700 | Lima | Peru | ||
125 | Teva Investigational Site 701 | Lima | Peru | ||
126 | Teva Investigational Site 704 | Lima | Peru | ||
127 | Teva Investigational Site 702 | Miraflores | Peru | ||
128 | Teva Investigational Site 703 | Miraflores | Peru |
Sponsors and Collaborators
- Teva Branded Pharmaceutical Products R&D, Inc.
Investigators
- Study Director: Sponsor's Medical Expert, Cephalon
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- C18083/3064/NL/MN
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | A total of 568 participants were screened, and 121 were not randomized (2 due to adverse event, 14 withdrew consent, 68 did not meet inclusion criteria, 23 met exclusion criteria, and 14 for other reasons). |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Period Title: Treatment Period | ||
STARTED | 224 | 223 |
COMPLETED | 199 | 196 |
NOT COMPLETED | 25 | 27 |
Period Title: Treatment Period | ||
STARTED | 210 | 209 |
COMPLETED | 157 | 154 |
NOT COMPLETED | 53 | 55 |
Baseline Characteristics
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP | Total |
---|---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 | Total of all reporting groups |
Overall Participants | 224 | 223 | 447 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
60.0
(11.37)
|
58.2
(12.11)
|
59.1
(11.77)
|
Sex: Female, Male (Count of Participants) | |||
Female |
88
39.3%
|
91
40.8%
|
179
40%
|
Male |
136
60.7%
|
132
59.2%
|
268
60%
|
European Cooperative Oncology Group Performance Status (participants) [Number] | |||
0 |
144
64.3%
|
143
64.1%
|
287
64.2%
|
1 |
70
31.3%
|
69
30.9%
|
139
31.1%
|
2 |
9
4%
|
10
4.5%
|
19
4.3%
|
3 |
1
0.4%
|
0
0%
|
1
0.2%
|
4 |
0
0%
|
0
0%
|
0
0%
|
Weight (kg) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [kg] |
81.9
(18.48)
|
82.4
(17.93)
|
82.1
(18.19)
|
Outcome Measures
Title | Percentage of Participants With Complete Response (CR) at End of Treatment Period |
---|---|
Description | CR=complete disappearance of all detectable clinical evidence of disease and disease-related symptoms, if present pretherapy; protocol-specified positron emission tomography (PET) scan assessment criteria; (if the spleen and/or liver were enlarged on the basis of physical examination and/or anatomic imaging before treatment) the liver and/or spleen were considered normal size on physical examination and by anatomic imaging after therapy, with disappearance of all nodules related to lymphoma; (if the bone marrow was involved by lymphoma before treatment) the infiltrate must have cleared on subsequent bone marrow biopsies. |
Time Frame | 6 to 8 21 or 28-day cycles (18-32 weeks) |
Outcome Measure Data
Analysis Population Description |
---|
Evaluable Analysis Set: treated participants with a baseline and >=1 post-baseline response evaluation (based on computed tomography/magnetic resonance imaging [CT/MRI] or positron emission tomography [PET] and clinical data), or who discontinued treatment due to progressive disease and had no major protocol violations. |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 213 | 206 |
Number (95% Confidence Interval) [percentage of participants] |
31
13.8%
|
25
11.2%
|
Title | Percentage of Participants With Overall Response at End of Treatment Period |
---|---|
Description | Overall Response=participants with Complete Remission (CR) + those with Partial Remission (PR). CR=see Outcome Measure 1 for details. PR= at least a 50% decrease in the sum of the product of the greatest diameters (SPD) of up to 6 of the largest dominant nodes/masses; at least a 50% decrease in the SPD of hepatic and splenic nodules in their greatest transverse diameter; no increase in the size of the liver, spleen, and other nodes; no measurable disease in organs other than the liver or spleen; no new sites of disease; protocol-specified PET scan and bone marrow criteria. |
Time Frame | 6 to 8 21 or 28-day cycles (18-32 weeks) |
Outcome Measure Data
Analysis Population Description |
---|
Evaluable Analysis Set: treated participants with a baseline and >=1 post-baseline response evaluation (based on computed tomography/magnetic resonance imaging [CT/MRI] or positron emission tomography [PET] and clinical data), or who discontinued treatment due to progressive disease and had no major protocol violations. |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 213 | 206 |
Number (95% Confidence Interval) [percentage of participants] |
97
43.3%
|
91
40.8%
|
Title | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs at End of Treatment Period |
---|---|
Description | AE=any untoward medical occurrence that develops or worsens in severity after dispensation of the study drug and does not necessarily have a causal relationship to the study drug. An AE can, therefore, be any unfavorable and unintended physical sign, symptom, or laboratory parameter that develops or worsens in severity during the course of the study, or significant worsening of the disease under study (or any concurrent disease), whether or not considered related to the study drug. AEs were graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). SAE=an adverse event occurring at any dose that results in: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity (a substantial disruption of one's ability to conduct normal life functions), a congenital anomaly/birth defect, or other important medical event. |
Time Frame | 32 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen. |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 221 | 215 |
Any AE |
221
98.7%
|
213
95.5%
|
Severe AEs (grades 3, 4, 5) |
130
58%
|
127
57%
|
Treatment-related AEs |
209
93.3%
|
NA
NaN
|
Deaths |
12
5.4%
|
9
4%
|
SAEs |
60
26.8%
|
49
22%
|
Withdrawn due to AEs |
10
4.5%
|
3
1.3%
|
Title | Worst Overall Common Terminology Criteria for Adverse Events (CTCAE) Grades for Serum Chemistry Laboratory Test Results |
---|---|
Description | Clinical laboratory data were graded according to National Cancer Institute's (NCI) CTCAE version 3, and graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). The table presents the worst CTCAE grades for serum chemistry test results experienced by participants overall (i.e., the worst post-baseline grade value for each participant and laboratory test across all cycles). |
Time Frame | 32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit) |
Outcome Measure Data
Analysis Population Description |
---|
Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen and who had a post-baseline assessment. |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 221 | 215 |
Albumin: Grade 1 |
33
14.7%
|
44
19.7%
|
Albumin: Grade 2 |
14
6.3%
|
13
5.8%
|
Albumin: Grade 3 |
3
1.3%
|
0
0%
|
Albumin: Grade 4 |
0
0%
|
0
0%
|
Albumin: Grades 1-4 |
50
22.3%
|
57
25.6%
|
Alkaline Phosphatase: Grade 1 |
41
18.3%
|
25
11.2%
|
Alkaline Phosphatase: Grade 2 |
1
0.4%
|
3
1.3%
|
Alkaline Phosphatase: Grade 3 |
0
0%
|
0
0%
|
Alkaline Phosphatase: Grade 4 |
0
0%
|
0
0%
|
Alkaline Phosphatase: Grades 1-4 |
42
18.8%
|
28
12.6%
|
Creatinine: Grade 1 |
19
8.5%
|
25
11.2%
|
Creatinine: Grade 2 |
3
1.3%
|
1
0.4%
|
Creatinine: Grade 3 |
1
0.4%
|
0
0%
|
Creatinine: Grade 4 |
0
0%
|
0
0%
|
Creatinine: Grades 1-4 |
23
10.3%
|
26
11.7%
|
Gamma-glutamyl transferase: Grade 1 |
31
13.8%
|
37
16.6%
|
Gamma-glutamyl transferase: Grade 2 |
18
8%
|
10
4.5%
|
Gamma-glutamyl transferase: Grade 3 |
3
1.3%
|
6
2.7%
|
Gamma-glutamyl transferase: Grade 4 |
0
0%
|
0
0%
|
Gamma-glutamyl transferase: Grades 1-4 |
52
23.2%
|
53
23.8%
|
Hypercalcemia: Grade 1 |
6
2.7%
|
6
2.7%
|
Hypercalcemia: Grade 2 |
0
0%
|
0
0%
|
Hypercalcemia: Grade 3 |
1
0.4%
|
0
0%
|
Hypercalcemia: Grade 4 |
0
0%
|
0
0%
|
Hypercalcemia: Grades 1-4 |
7
3.1%
|
6
2.7%
|
Hyperglycemia: Grade 1 |
94
42%
|
74
33.2%
|
Hyperglycemia: Grade 2 |
20
8.9%
|
34
15.2%
|
Hyperglycemia: Grade 3 |
15
6.7%
|
15
6.7%
|
Hyperglycemia: Grade 4 |
0
0%
|
1
0.4%
|
Hyperglycemia: Grades 1-4 |
129
57.6%
|
124
55.6%
|
Hyperkalemia: Grade 1 |
7
3.1%
|
8
3.6%
|
Hyperkalemia: Grade 2 |
3
1.3%
|
1
0.4%
|
Hyperkalemia: Grade 3 |
1
0.4%
|
0
0%
|
Hyperkalemia: Grade 4 |
0
0%
|
0
0%
|
Hyperkalemia: Grades 1-4 |
11
4.9%
|
9
4%
|
Hypernatremia: Grade 1 |
8
3.6%
|
10
4.5%
|
Hypernatremia: Grade 2 |
0
0%
|
0
0%
|
Hypernatremia: Grade 3 |
0
0%
|
0
0%
|
Hypernatremia: Grade 4 |
0
0%
|
0
0%
|
Hypernatremia: Grades 1-4 |
8
3.6%
|
10
4.5%
|
Hypocalcemia: Grade 1 |
36
16.1%
|
28
12.6%
|
Hypocalcemia: Grade 2 |
8
3.6%
|
6
2.7%
|
Hypocalcemia: Grade 3 |
1
0.4%
|
0
0%
|
Hypocalcemia: Grade 4 |
3
1.3%
|
0
0%
|
Hypocalcemia: Grades 1-4 |
48
21.4%
|
34
15.2%
|
Hypoglycemia: Grade 1 |
15
6.7%
|
10
4.5%
|
Hypoglycemia: Grade 2 |
1
0.4%
|
0
0%
|
Hypoglycemia: Grade 3 |
0
0%
|
0
0%
|
Hypoglycemia: Grade 4 |
0
0%
|
0
0%
|
Hypoglycemia: Grades 1-4 |
16
7.1%
|
10
4.5%
|
Hypokalemia: Grade 1 |
18
8%
|
16
7.2%
|
Hypokalemia: Grade 2 |
0
0%
|
0
0%
|
Hypokalemia: Grade 3 |
0
0%
|
1
0.4%
|
Hypokalemia: Grade 4 |
0
0%
|
0
0%
|
Hypokalemia: Grades 1-4 |
18
8%
|
17
7.6%
|
Hyponatremia: Grade 1 |
40
17.9%
|
28
12.6%
|
Hyponatremia: Grade 2 |
0
0%
|
0
0%
|
Hyponatremia: Grade 3 |
0
0%
|
5
2.2%
|
Hyponatremia: Grade 4 |
0
0%
|
0
0%
|
Hyponatremia: Grades 1-4 |
40
17.9%
|
33
14.8%
|
Magnesium: Grade 1 |
46
20.5%
|
44
19.7%
|
Magnesium: Grade 2 |
0
0%
|
1
0.4%
|
Magnesium: Grade 3 |
0
0%
|
1
0.4%
|
Magnesium: Grade 4 |
0
0%
|
0
0%
|
Magnesium: Grades 1-4 |
46
20.5%
|
46
20.6%
|
Phosphorus: Grade 1 |
7
3.1%
|
5
2.2%
|
Phosphorus: Grade 2 |
25
11.2%
|
22
9.9%
|
Phosphorus: Grade 3 |
3
1.3%
|
3
1.3%
|
Phosphorus: Grade 4 |
0
0%
|
1
0.4%
|
Phosphorus: Grades 1-4 |
35
15.6%
|
31
13.9%
|
Aspartate Aminotransferase: Grade 1 |
42
18.8%
|
32
14.3%
|
Aspartate Aminotransferase: Grade 2 |
2
0.9%
|
2
0.9%
|
Aspartate Aminotransferase: Grade 3 |
1
0.4%
|
1
0.4%
|
Aspartate Aminotransferase: Grade 4 |
0
0%
|
0
0%
|
Aspartate Aminotransferase: Grades 1-4 |
45
20.1%
|
35
15.7%
|
Alanine Aminotransferase: Grade 1 |
46
20.5%
|
38
17%
|
Alanine Aminotransferase: Grade 2 |
6
2.7%
|
3
1.3%
|
Alanine Aminotransferase: Grade 3 |
2
0.9%
|
1
0.4%
|
Alanine Aminotransferase: Grade 4 |
0
0%
|
0
0%
|
Alanine Aminotransferase: Grades 1-4 |
54
24.1%
|
42
18.8%
|
Total Bilirubin: Grade 1 |
14
6.3%
|
7
3.1%
|
Total Bilirubin: Grade 2 |
1
0.4%
|
0
0%
|
Total Bilirubin: Grade 3 |
0
0%
|
0
0%
|
Total Bilirubin: Grade 4 |
0
0%
|
0
0%
|
Total Bilirubin: Grades 1-4 |
15
6.7%
|
7
3.1%
|
Uric Acid: Grade 1 |
41
18.3%
|
42
18.8%
|
Uric Acid: Grade 2 |
0
0%
|
0
0%
|
Uric Acid: Grade 3 |
0
0%
|
0
0%
|
Uric Acid: Grade 4 |
1
0.4%
|
0
0%
|
Uric Acid: Grades 1-4 |
42
18.8%
|
42
18.8%
|
Title | Worst Overall CTCAE Grade for Hematology Laboratory Test Results |
---|---|
Description | Hematology test data were graded according to National Cancer Institute's (NCI) CTCAE version 3, and graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). The table presents the worst CTCAE grades for hematology test results experienced by participants overall (i.e., the worst post-baseline grade value for each participant and hematology test across all cycles). |
Time Frame | 32 weeks (conducted at screening, Day 1 of each cycle, weekly during treatment, and at the end-of-treatment visit) |
Outcome Measure Data
Analysis Population Description |
---|
Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen and who had an assessment. |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 221 | 215 |
Absolute Neutrophil Count: Grade 1 |
22
9.8%
|
14
6.3%
|
Absolute Neutrophil Count: Grade 2 |
51
22.8%
|
20
9%
|
Absolute Neutrophil Count: Grade 3 |
48
21.4%
|
47
21.1%
|
Absolute Neutrophil Count: Grade 4 |
50
22.3%
|
104
46.6%
|
Absolute Neutrophil Count: Grades 1-4 |
171
76.3%
|
185
83%
|
Hemoglobin: Grade 1 |
129
57.6%
|
129
57.8%
|
Hemoglobin: Grade 2 |
42
18.8%
|
51
22.9%
|
Hemoglobin: Grade 3 |
5
2.2%
|
7
3.1%
|
Hemoglobin: Grade 4 |
1
0.4%
|
2
0.9%
|
Hemoglobin: Grades 1-4 |
177
79%
|
189
84.8%
|
Lymphocytes Absolute: Grade 1 |
1
0.4%
|
6
2.7%
|
Lymphocytes Absolute: Grade 2 |
5
2.2%
|
55
24.7%
|
Lymphocytes Absolute: Grade 3 |
54
24.1%
|
55
24.7%
|
Lymphocytes Absolute: Grade 4 |
83
37.1%
|
9
4%
|
Lymphocytes Absolute: Grades 1-4 |
143
63.8%
|
125
56.1%
|
Platelets: Grade 1 |
106
47.3%
|
72
32.3%
|
Platelets: Grade 2 |
14
6.3%
|
14
6.3%
|
Platelets: Grade 3 |
9
4%
|
7
3.1%
|
Platelets: Grade 4 |
7
3.1%
|
8
3.6%
|
Platelets: Grades 1-4 |
136
60.7%
|
101
45.3%
|
White Blood Cells: Grade 1 |
41
18.3%
|
22
9.9%
|
White Blood Cells: Grade 2 |
79
35.3%
|
49
22%
|
White Blood Cells: Grade 3 |
65
29%
|
89
39.9%
|
White Blood Cells: Grade 4 |
19
8.5%
|
27
12.1%
|
White Blood Cells: Grades 1-4 |
204
91.1%
|
187
83.9%
|
Title | Clinically Significant Abnormal Vital Signs |
---|---|
Description | |
Time Frame | 32 weeks (conducted at screening, Day 1 of each cycle, and end-of-treatment visit) |
Outcome Measure Data
Analysis Population Description |
---|
Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen and had baseline and post-baseline values. |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 220 | 212 |
Heart Rate >=120 and ↑ >=15 bpm |
0
0%
|
1
0.4%
|
Heart Rate <=50 and ↓ >=15 bpm |
2
0.9%
|
2
0.9%
|
Systolic Blood Pressure(BP) >=180 and ↑ >=20 mm Hg |
2
0.9%
|
2
0.9%
|
Systolic BP <=90 and ↓ >=20 mm Hg |
6
2.7%
|
2
0.9%
|
Diastolic BP >=105 and ↑ from Baseline >=15 mm Hg |
1
0.4%
|
2
0.9%
|
Diastolic BP <=50 and ↓ from Baseline >=15 mm Hg |
2
0.9%
|
2
0.9%
|
Title | Potentially Clinically Significant Abnormal Weight |
---|---|
Description | Participants were weighed at Baseline and at Endpoint (Week 32); those participants with an increase or decrease of >=10% were considered potentially clinically significant. |
Time Frame | Baseline, Week 32 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen with a baseline and post-baseline weight. |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 220 | 212 |
Increase >=10% |
8
3.6%
|
5
2.2%
|
Decrease >=10% |
18
8%
|
8
3.6%
|
Title | Eastern Cooperative Oncology Group (ECOG) Performance Status at the End of Treatment Period |
---|---|
Description | Participants' ECOG Performance Status was evaluated at the end of treatment as improved, stayed the same, or worsened from baseline (see Baseline Characteristics for ECOG Performance Status). |
Time Frame | Week 32 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen and with baseline and post-baseline values. |
Arm/Group Title | Bendamustine/Rituximab | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | bendamustine at 90 mg/m2 iv on days 1 and 2 and rituximab at 375 mg/m2 iv infusion on day 1 | R-CHOP, consisting of rituximab at 375 mg/m2 iv on day 1, vincristine at 1.4 mg /m2 (up to a maximum dose of 2 mg iv) by iv on day 1, prednisone at 100 mg orally on days 1 to 5 of a 21-day cycle, doxorubicin at 50 mg/m2 by iv over 3-5 minutes on day 1, cyclophosphamide iv at 750 mg/m2 on day 1. R-CVP consisting of rituximab at 375 mg/m2 iv on day 1, vincristine at 1.4 mg /m2 (up to a maximum dose of 2 mg iv) by iv on day 1, prednisone at 100 mg orally on days 1 to 5 of a 21-day cycle, only 1 of the following doses of cyclophosphamide throughout the study: cyclophosphamide at 750 mg/m2 iv on day 1 or cyclophosphamide at 1000 mg/m2 iv on day 1. |
Measure Participants | 219 | 211 |
Improved |
32
14.3%
|
28
12.6%
|
Stayed the Same |
153
68.3%
|
141
63.2%
|
Worsened |
34
15.2%
|
42
18.8%
|
Title | Therapeutic Classification of Prior Medications |
---|---|
Description | |
Time Frame | prior to start of treatment |
Outcome Measure Data
Analysis Population Description |
---|
Safety Analysis Set: all participants randomly assigned to a treatment group |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 224 | 223 |
Psycholeptics |
57
25.4%
|
59
26.5%
|
Sex Hormones and Modulators of the Genital System |
11
4.9%
|
12
5.4%
|
Stomatological Preparations |
0
0%
|
0
0%
|
Throat Preparations |
0
0%
|
0
0%
|
Thyroid Therapy |
16
7.1%
|
17
7.6%
|
Topical Products for Join and Muscular Pain |
1
0.4%
|
0
0%
|
Unspecified Herbal |
10
4.5%
|
10
4.5%
|
Urologicals |
20
8.9%
|
11
4.9%
|
Vaccines |
2
0.9%
|
7
3.1%
|
Vasoprotectives |
0
0%
|
0
0%
|
Vitamins |
70
31.3%
|
61
27.4%
|
Title | Therapeutic Classification of Concomitant Medications |
---|---|
Description | |
Time Frame | 32 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Safety Analysis Set: all participants randomly assigned to a treatment group who received 1 or more doses of any component of any study drug regimen. |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 221 | 215 |
Psycholeptics |
69
30.8%
|
74
33.2%
|
Sex Hormones and Modulators of the Genital System |
6
2.7%
|
4
1.8%
|
Stomatological Preparations |
23
10.3%
|
29
13%
|
Throat Preparations |
3
1.3%
|
2
0.9%
|
Thyroid Therapy |
3
1.3%
|
1
0.4%
|
Topical Preparations for Join and Muscular Pain |
1
0.4%
|
2
0.9%
|
Unspecified Herbal |
3
1.3%
|
5
2.2%
|
Urologicals |
5
2.2%
|
4
1.8%
|
Vaccines |
11
4.9%
|
11
4.9%
|
Vasoprotectives |
1
0.4%
|
8
3.6%
|
Vitamins |
16
7.1%
|
21
9.4%
|
Title | Change From Baseline to End of Treatment in the Global Health Status Score of the European Organization for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire (QLQ-C30) |
---|---|
Description | EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). This outcome reports the global health status on a scale of 0-100 with a high score for the global health status/QOL represents a high quality of life. |
Time Frame | Day 1 (prior to treatment), 32 weeks |
Outcome Measure Data
Analysis Population Description |
---|
The set of randomized participants (intent-to-treat) consisting of all patients randomly assigned to treatment, and who had data at both timepoints. |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 211 | 207 |
Mean (Standard Deviation) [units on a scale] |
3.6
(24.60)
|
-5.1
(24.50)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Bendamustine and Rituximab (BR), R-CHOP/R-CVP |
---|---|---|
Comments | The hypothesis of interest is superiority of BR over standard treatment. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0005 |
Comments | P-value for the treatment comparison is from an analysis of covariance (ANCOVA) with treatment group, region, preassigned standard treatment, and lymphoma type as factors and baseline value as the covariate. | |
Method | ANCOVA | |
Comments |
Title | Participants With Disease Progression, Relapse or Death At the End of the Treatment Period or the Long-Term Follow-up Period |
---|---|
Description | Relapsed disease (after CR) and progressive disease (PD) (after PR or SD): Lymph nodes were considered abnormal if the long axis was greater than 1.5 cm. Lymph nodes with a long axis of 1.1 to 1.5 cm were considered abnormal if its short axis was greater than 1.0 cm. In patients with no prior history of pulmonary lymphoma, new lung nodules identified by CT require histologic confirmation. >= 50% increase from nadir in sum of the products of the greatest diameters (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions (eg, splenic or hepatic nodules). To be considered progressive disease, a lymph node with a diameter of the short axis of less than 1.0 cm must have increased by 2: 50% and to a size of 1.5 cm by 1.5 cm, or more than 1.5 cm in the long axis other conditions as specified in the protocol |
Time Frame | Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period |
Outcome Measure Data
Analysis Population Description |
---|
Randomized patients: the set of randomized patients (intent-to-treat) consists of all patients randomly assigned to treatment. |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 224 | 223 |
Count of Participants [Participants] |
36
16.1%
|
30
13.5%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Bendamustine and Rituximab (BR), R-CHOP/R-CVP |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.9677 |
Comments | ||
Method | Log Rank | |
Comments | Stratified log-rank test by preassigned standard treatment and lymphoma type. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.99 | |
Confidence Interval |
(2-Sided) 95% 0.58 to 1.68 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | BR/RCHOP-RCVP |
Title | Kaplan-Meier Estimate for Progression-free Survival (PFS) |
---|---|
Description | PFS was defined as the time from randomization to disease progression or relapse, or death from any cause, whichever occurred first. |
Time Frame | Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period) |
Outcome Measure Data
Analysis Population Description |
---|
Randomized patients |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 224 | 223 |
Median (95% Confidence Interval) [months] |
31.8
|
33.4
|
Title | Kaplan-Meier Estimate for Event-free Survival (EFS) |
---|---|
Description | EFS was defined as the time from randomization to treatment failure, disease progression or relapse, other malignancies, or death from any cause, whichever occurred first. Treatment failure was defined as failure to achieve a CR or PR after 6 cycles of treatment. If a patient failed to achieve CR or PR by the time of data analysis or early withdrawal, the treatment failure date was set at 126 days (6 cycles of treatment) after randomization or the new anticancer treatment date, whichever is earlier. |
Time Frame | Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period) |
Outcome Measure Data
Analysis Population Description |
---|
Randomized patients |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 224 | 223 |
Median (95% Confidence Interval) [months] |
31.8
|
32.6
|
Title | Kaplan-Meier Estimate for Duration of Response (DOR) |
---|---|
Description | DOR was defined as the time from first response (CR or PR) to disease progression or relapse, or death due to any cause. |
Time Frame | Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period) |
Outcome Measure Data
Analysis Population Description |
---|
Randomized patients with complete response (CR) or partial response (PR) |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 210 | 187 |
Median (95% Confidence Interval) [months] |
26.5
|
32.1
|
Title | Overall Survival (OS) |
---|---|
Description | OS was defined as the time from randomization to death from any cause. |
Time Frame | Day 1 up to 5.6 years (Treatment Period + Long-Term Follow-up Period) |
Outcome Measure Data
Analysis Population Description |
---|
Randomized patients |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 224 | 223 |
Median (95% Confidence Interval) [months] |
65.0
|
64.1
|
Title | Participants Who Died At the End of the Treatment Period or the Long-Term Follow-up Period |
---|---|
Description | Death is due to any cause. Data are broken out by patients who died within 30 days of the last dose of study medications, and those who died greater than 30 days of the last dose of study medications. |
Time Frame | Treatment Period: 18-32 weeks Long-Term Follow-up Period: up to 5 years after the Treatment Period |
Outcome Measure Data
Analysis Population Description |
---|
Randomized patients: the set of randomized patients (intent-to-treat) consists of all patients randomly assigned to treatment. |
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/R-CVP |
---|---|---|
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 |
Measure Participants | 224 | 223 |
All Deaths |
40
17.9%
|
32
14.3%
|
Deaths within 30 days of study treatment |
2
0.9%
|
1
0.4%
|
Deaths greater than 30 days of study treatment |
38
17%
|
31
13.9%
|
Adverse Events
Time Frame | Treatment Period: 32 weeks No adverse event data was collected during the 5-year Long-Term Follow-Up Period | |||
---|---|---|---|---|
Adverse Event Reporting Description | Events are reported for the safety analysis set (participants who received at least 1 dose of study drug). | |||
Arm/Group Title | Bendamustine and Rituximab (BR) | R-CHOP/CVP | ||
Arm/Group Description | Participants received the investigational bendamustine and rituximab regimen for 6 to 8 28-day cycles: bendamustine 90 mg/m^2 intravenous (IV) on Days 1 and 2; rituximab 375 mg/m^2 IV on Day 1. | Participants received the standard regimen (R-CHOP or R-CVP) for 6 to 8 21-days cycles. R-CHOP: rituximab 375 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; doxorubicin 50 mg/m^2 IV Day 1; cyclophosphamide 750 mg/m^2 IV Day 1; prednisone 100 mg oral on Days 1 to 5 R-CVP: rituximab 375 mg/m^2 IV on Day 1; cyclophosphamide 750 mg/m^2 IV on Day 1 or cyclophosphamide 1000 mg/m^2 IV on Day 1; vincristine 1.4 mg/m^2 (up to 2 mg/m^2 maximum dose) IV on Day 1; prednisone 100 mg oral on Days 1 to 5 | ||
All Cause Mortality |
||||
Bendamustine and Rituximab (BR) | R-CHOP/CVP | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Bendamustine and Rituximab (BR) | R-CHOP/CVP | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 60/221 (27.1%) | 49/215 (22.8%) | ||
Blood and lymphatic system disorders | ||||
Aplasia pure red cell | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Febrile neutropenia | 7/221 (3.2%) | 8 | 9/215 (4.2%) | 10 |
Lymphadenopathy | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Neutropenia | 4/221 (1.8%) | 6 | 5/215 (2.3%) | 6 |
Splenomegaly | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Cardiac disorders | ||||
Atrial fibrillation | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Atrioventricular block first degree | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Bundle branch block left | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Cardiac arrest | 1/221 (0.5%) | 1 | 1/215 (0.5%) | 1 |
Cardiac failure congestive | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Left ventricular dysfunction | 1/221 (0.5%) | 1 | 1/215 (0.5%) | 2 |
Myocardial infarction | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Pericardial effusion | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Supraventricular tachycardia | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Eye disorders | ||||
Vitreous floaters | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Gastrointestinal disorders | ||||
Abdominal pain | 2/221 (0.9%) | 3 | 1/215 (0.5%) | 1 |
Ascites | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Constipation | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Diarrhoea | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Diverticular perforation | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Gastrooesophageal reflux disease | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Ileus | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Nausea | 3/221 (1.4%) | 3 | 0/215 (0%) | 0 |
Rectal haemorrhage | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Small intestinal obstruction | 1/221 (0.5%) | 1 | 1/215 (0.5%) | 1 |
Vomiting | 3/221 (1.4%) | 3 | 0/215 (0%) | 0 |
General disorders | ||||
Chills | 1/221 (0.5%) | 2 | 0/215 (0%) | 0 |
Non-cardiac chest pain | 0/221 (0%) | 0 | 3/215 (1.4%) | 3 |
Pyrexia | 5/221 (2.3%) | 6 | 4/215 (1.9%) | 5 |
Hepatobiliary disorders | ||||
Cholelithiasis | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Portal vein thrombosis | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Immune system disorders | ||||
Anaphylactic shock | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Drug hypersensitivity | 4/221 (1.8%) | 4 | 0/215 (0%) | 0 |
Infections and infestations | ||||
Abscess limb | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Anal infection | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Bacteraemia | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Clostridium difficile colitis | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Diverticulitis | 2/221 (0.9%) | 3 | 1/215 (0.5%) | 1 |
Gastroenteritis | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Gastrointestinal infection | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Infection | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Infective exacerbation of chronic obstructive airways disease | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Lower respiratory tract infection | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Pharyngitis | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Pneumocystis jiroveci infection | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Pneumocystis jiroveci pneumonia | 1/221 (0.5%) | 1 | 1/215 (0.5%) | 1 |
Pneumonia | 7/221 (3.2%) | 7 | 1/215 (0.5%) | 1 |
Postoperative wound infection | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Septic shock | 1/221 (0.5%) | 1 | 1/215 (0.5%) | 2 |
Tooth abscess | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Tooth infection | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Tracheobronchitis | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Upper respiratory tract infection | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Urinary tract infection | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Viral infection | 2/221 (0.9%) | 2 | 0/215 (0%) | 0 |
Injury, poisoning and procedural complications | ||||
Ankle fracture | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Cervical vertebral fracture | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Clavicle fracture | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Fall | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Infusion related reaction | 8/221 (3.6%) | 11 | 4/215 (1.9%) | 4 |
Procedural complication | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Rib fracture | 1/221 (0.5%) | 1 | 1/215 (0.5%) | 1 |
Spinal compression fracture | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Toxicity to various agents | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Investigations | ||||
Electrocardiogram QT prolonged | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Metabolism and nutrition disorders | ||||
Dehydration | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Hyperglycaemia | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Tumour lysis syndrome | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||
Back pain | 0/221 (0%) | 0 | 2/215 (0.9%) | 3 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Lung neoplasm malignant | 1/221 (0.5%) | 2 | 0/215 (0%) | 0 |
Renal cell carcinoma | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Sarcoma | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Nervous system disorders | ||||
Dystonia | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Headache | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Intracranial aneurysm | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Neuropathy peripheral | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Syncope | 1/221 (0.5%) | 1 | 1/215 (0.5%) | 1 |
Psychiatric disorders | ||||
Confusional state | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Depression | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Renal and urinary disorders | ||||
Haematuria | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Renal failure acute | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Renal tubular necrosis | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Urinary retention | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Reproductive system and breast disorders | ||||
Prostatitis | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||
Acute respiratory failure | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Chronic obstructive pulmonary disease | 2/221 (0.9%) | 3 | 0/215 (0%) | 0 |
Dyspnoea | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Hypoxia | 1/221 (0.5%) | 1 | 1/215 (0.5%) | 1 |
Interstitial lung disease | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Pleural effusion | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Pulmonary embolism | 1/221 (0.5%) | 1 | 1/215 (0.5%) | 1 |
Respiratory failure | 2/221 (0.9%) | 2 | 0/215 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||
Rash | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Rash maculo-papular | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Vascular disorders | ||||
Hypertension | 0/221 (0%) | 0 | 1/215 (0.5%) | 1 |
Hypotension | 1/221 (0.5%) | 1 | 0/215 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
Bendamustine and Rituximab (BR) | R-CHOP/CVP | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 216/221 (97.7%) | 211/215 (98.1%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 31/221 (14%) | 63 | 29/215 (13.5%) | 69 |
Febrile neutropenia | 7/221 (3.2%) | 9 | 11/215 (5.1%) | 12 |
Leukopenia | 21/221 (9.5%) | 79 | 22/215 (10.2%) | 88 |
Lymphopenia | 14/221 (6.3%) | 104 | 12/215 (5.6%) | 44 |
Neutropenia | 76/221 (34.4%) | 251 | 85/215 (39.5%) | 255 |
Thrombocytopenia | 29/221 (13.1%) | 67 | 13/215 (6%) | 54 |
Gastrointestinal disorders | ||||
Abdominal pain | 25/221 (11.3%) | 33 | 27/215 (12.6%) | 31 |
Abdominal pain upper | 11/221 (5%) | 11 | 14/215 (6.5%) | 16 |
Constipation | 65/221 (29.4%) | 85 | 90/215 (41.9%) | 121 |
Diarrhoea | 46/221 (20.8%) | 65 | 50/215 (23.3%) | 72 |
Dyspepsia | 23/221 (10.4%) | 23 | 26/215 (12.1%) | 29 |
Gastrooesophageal reflux disease | 16/221 (7.2%) | 16 | 17/215 (7.9%) | 18 |
Nausea | 139/221 (62.9%) | 255 | 102/215 (47.4%) | 139 |
Stomatitis | 15/221 (6.8%) | 20 | 14/215 (6.5%) | 17 |
Vomiting | 60/221 (27.1%) | 86 | 28/215 (13%) | 35 |
General disorders | ||||
Asthenia | 14/221 (6.3%) | 16 | 17/215 (7.9%) | 24 |
Chest discomfort | 8/221 (3.6%) | 10 | 13/215 (6%) | 14 |
Chills | 25/221 (11.3%) | 34 | 11/215 (5.1%) | 14 |
Fatigue | 113/221 (51.1%) | 179 | 107/215 (49.8%) | 147 |
Mucosal inflammation | 12/221 (5.4%) | 15 | 26/215 (12.1%) | 36 |
Oedema peripheral | 19/221 (8.6%) | 23 | 23/215 (10.7%) | 27 |
Pain | 14/221 (6.3%) | 15 | 14/215 (6.5%) | 17 |
Pyrexia | 37/221 (16.7%) | 45 | 28/215 (13%) | 31 |
Immune system disorders | ||||
Drug hypersensitivity | 24/221 (10.9%) | 32 | 8/215 (3.7%) | 9 |
Infections and infestations | ||||
Nasopharyngitis | 9/221 (4.1%) | 9 | 11/215 (5.1%) | 11 |
Sinusitis | 5/221 (2.3%) | 7 | 12/215 (5.6%) | 14 |
Upper respiratory tract infection | 22/221 (10%) | 26 | 17/215 (7.9%) | 20 |
Injury, poisoning and procedural complications | ||||
Infusion related reaction | 52/221 (23.5%) | 115 | 45/215 (20.9%) | 64 |
Investigations | ||||
Neutrophil count decreased | 9/221 (4.1%) | 15 | 12/215 (5.6%) | 18 |
Weight decreased | 14/221 (6.3%) | 14 | 7/215 (3.3%) | 8 |
Metabolism and nutrition disorders | ||||
Decreased appetite | 42/221 (19%) | 57 | 26/215 (12.1%) | 26 |
Hyperglycaemia | 4/221 (1.8%) | 9 | 11/215 (5.1%) | 26 |
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 28/221 (12.7%) | 33 | 32/215 (14.9%) | 46 |
Back pain | 23/221 (10.4%) | 26 | 27/215 (12.6%) | 39 |
Bone pain | 9/221 (4.1%) | 10 | 18/215 (8.4%) | 20 |
Muscle spasms | 6/221 (2.7%) | 6 | 11/215 (5.1%) | 14 |
Musculoskeletal pain | 12/221 (5.4%) | 12 | 17/215 (7.9%) | 18 |
Myalgia | 13/221 (5.9%) | 15 | 18/215 (8.4%) | 21 |
Pain in extremity | 17/221 (7.7%) | 23 | 18/215 (8.4%) | 20 |
Nervous system disorders | ||||
Dizziness | 18/221 (8.1%) | 31 | 21/215 (9.8%) | 29 |
Dysgeusia | 28/221 (12.7%) | 32 | 25/215 (11.6%) | 25 |
Headache | 48/221 (21.7%) | 60 | 45/215 (20.9%) | 68 |
Neuropathy peripheral | 9/221 (4.1%) | 13 | 51/215 (23.7%) | 77 |
Paraesthesia | 7/221 (3.2%) | 8 | 25/215 (11.6%) | 29 |
Peripheral sensory neuropathy | 4/221 (1.8%) | 4 | 20/215 (9.3%) | 24 |
Psychiatric disorders | ||||
Anxiety | 17/221 (7.7%) | 18 | 18/215 (8.4%) | 20 |
Insomnia | 37/221 (16.7%) | 42 | 47/215 (21.9%) | 53 |
Respiratory, thoracic and mediastinal disorders | ||||
Cough | 34/221 (15.4%) | 37 | 34/215 (15.8%) | 36 |
Dyspnoea | 17/221 (7.7%) | 23 | 26/215 (12.1%) | 28 |
Oropharyngeal pain | 18/221 (8.1%) | 20 | 16/215 (7.4%) | 18 |
Skin and subcutaneous tissue disorders | ||||
Alopecia | 8/221 (3.6%) | 8 | 74/215 (34.4%) | 83 |
Dry skin | 12/221 (5.4%) | 13 | 7/215 (3.3%) | 7 |
Night sweats | 7/221 (3.2%) | 7 | 15/215 (7%) | 15 |
Pruritus | 22/221 (10%) | 26 | 10/215 (4.7%) | 10 |
Rash | 33/221 (14.9%) | 40 | 17/215 (7.9%) | 20 |
Vascular disorders | ||||
Hypotension | 12/221 (5.4%) | 13 | 7/215 (3.3%) | 8 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Investigator/Institution must submit proposed publication to Sponsor for review within a prespecified number of days before submission for publication. If Sponsor's review shows that potentially patentable subject matter would be disclosed, publication/public disclosure shall be delayed to enable Sponsor, or Sponsor's designees, to file necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
Name/Title | Manager |
---|---|
Organization | Teva Pharmaceuticals USA |
Phone | 1-866-384-5525 |
clinicaltrialqueries@tevausa.com |
- C18083/3064/NL/MN