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ORCHARRD: Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT01014208
Collaborator
(none)
447
Enrollment
173
Locations
2
Arms
56
Duration (Months)
2.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is being conducted to compare the efficacy and safety of ofatumumab in addition to salvage chemotherapy versus rituximab in addition to salvage chemotherapy in CD20 positive DLBCL subjects relapsing, or with persistent disease, after first-line treatment with rituximab combined with an anthracycline-based chemotherapy regimen and be eligible for ASCT.

Condition or Disease Intervention/Treatment Phase
  • Drug: OFATUMUMAB + DHAP
  • Drug: RITUXIMAB + DHAP
 Phase 3

Detailed Description

As rituximab-based regimens have become standard first-line treatment in CD20 positive DLBCL, the efficacy of rituximab combined with salvage chemotherapy in the second-line setting has decreased and there is a need for new therapies in patients progressing or relapsing after first-line rituximab-based therapy. Replacement of rituximab with ofatumumab in the second-line setting, following progression/relapse after first-line rituximab-containing regimens, offers the potential to overcome relative or complete rituximab resistance and thus improve response rates, the ability to proceed to consolidative HDT/ASCT, and overall survival.

Study Design

Study Type:
Interventional
Actual Enrollment :
447 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant (ASCT) in Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)
Study Start Date :
Mar 1, 2010
Actual Primary Completion Date :
Feb 1, 2014
Actual Study Completion Date :
Nov 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: OFATUMUMAB + DHAP CHEMOTHERAPY REGIMEN

This study is a parallel arm study, with ofatumumab + DHAP. The Investigators are required to prospectively choose to treat all of their subjects with either DHAP chemotherapy regimens in combination with ofatumumab. All subjects will receive the same ofatumumab regimen and dose.

Drug: OFATUMUMAB + DHAP
3 cycles of treatment will be administered. Each cycle will last 21 days. ofatumumab dose: cycle 1, day 1 - 1000 mg; cycle 1, day 8 - 1000 mg; cycle 2, day 1 and cycle 3, day 1 - 1000 mg. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m2/24hrs continuous on day 1 of dosing cycle; cytarabine - 2g/m2 q12 hrs (2 doses) on day 2 of dosing cycle.
Active Comparator: RITUXIMAB + DHAP CHEMOTHERAPY REGIMEN

This study is a parallel arm study, with rituximab + DHAP. The Investigators are required to prospectively choose to treat all of their subjects with either DHAP chemotherapy regimens in combination with rituximab. All subjects will receive the same rituximab regimen and dose.

Drug: RITUXIMAB + DHAP
3 cycles of treatment will be administered. Each cycle will last 21 days. rituximab dose: cycle 1, day 1 - 375 mg/m2; cycle 1, day 8 - 375 mg/m2; cycle 2, day 1 and cycle 3, day 1 - 375 mg/m2. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m2/24hrs continuous on day 1 of dosing cycle; cytarabine - 2g/m2 q12 hrs (2 doses) on day 2 of dosing cycle.

Outcome Measures

Primary Outcome Measures

  1. Progression-free Survival as Assessed by Independent Reviewers [From randomization until the date of stable disease after two cycles of salvage chemotherapy, progression, or death (assessed for up to 5 years)]

    Progression-free survival is defined as the interval of time from the randomization date until the date of stable disease (SD; failure to attain the criteria needed for a CR or PR and no fulfillment of the criteria for progressive disease [PD]) after two cycles of salvage chemotherapy, progression, or death, whichever occurs first. Disease progression was based on the assessments of independent reviewers for the disease under study. Disease progression was based on imaging data via the Revised Response Criteria for Malignant Lymphoma (RRCML).

Secondary Outcome Measures

  1. Number of Participants With Overall Response (OR) and Complete Response (CR) After Salvage Chemoimmunotherapy [At completion of up to 3 cycles of salvage chemoimmunotherapy (assessed up to 9 weeks)]

    OR is defined as the number of participants achieving either a complete response (CR) or a partial response (PR). CR is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR is defined as at least a 50% decrease from Baseline in the sum of the product of the diameters of target lesions. RRCML was used to assess CR and PR.

  2. Number of Participants With Overall Response (OR) and Complete Response (CR) Three Months After Autologous Stem Cell Transplant [At 3 months after completion of autologous stem cell transplantation (ASCT) (assessed up to 6 months)]

    OR is defined as the number of participants achieving either a complete response (CR) or a partial response (PR). CR is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR is defined as at least a 50% decrease from Baseline in the sum of the product of the diameters of target lesions. RRCML was used to assess CR and PR.

  3. Event-free Survival [From randomization to progressive disease, stable disease after completion of 2 cycles of therapy, commencement of a new treatment for DLBCL, or death due to any cause (assessed for up to 5 years)]

    Event-free survival is defined as the time from randomization to progressive disease (PD; disease whose course is growth, or spread of the disease), stable disease (SD; failure to attain the criteria needed for a CR or PR and no fulfillment of the criteria for PD) after completion of 2 cycles of therapy, commencement of a new treatment for diffuse large B cell lymphoma (DLBCL) (e.g., radiotherapy), or death from any cause, whichever occurs first. Disease progression was based on the assessments of independent reviewers for the disease under study. Disease progression was based on imaging data via the Revised Response Criteria for Malignant Lymphoma (RRCML).

  4. Overall Survival (OS) [From randomization to death due to any cause (assessed for up to 5 years)]

    OS is defined as the time from randomization to death due to any cause. Participants who were still alive by the end of the study were censored.

  5. Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram From Peripheral Blood [During Cycles 2 and/or 3 (Weeks 4-9)]

    Stem cell mobilization is the process of stimulating the hematopoietic stem cells (CD34+) to move out of the bone marrow and into the bloodstream, where they can be collected via a process called apheresis. Successful mobilization is defined as the collection of >2*10^6 CD34+ cells/kg. Only those participants, who commenced harvest, following the administration of rituximab or ofatumumab in combination with DHAP combination chemotherapy, were assessed. The number of participants with adequate harvest of CD34+ stem cells (at least 2*10^6 CD34+ cells/kg) after dosing of salvage therapy in Cycle 2 and Cycle 3 was analyzed.

  6. Number of Participants Completing Autologous Stem Cell Transplant (ASCT) [Approximately 4 to 6 weeks following Cycle 3 (assessed up to 3 months)]

    The number of participants who completed ASCT is reported.

  7. Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) During Treatment [Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months])]

    The FACT-G was developed by the Functional Assessment of Chronic Illness Therapy (FACIT) group for use in adults in a wide range of oncology clinical trial populations. The 27 items of the FACT-G are scored in the following domains: Physical Well-being (7 items), Social/Family Wellbeing (7 items), Emotional Well-being (6 items), and Functional Well-being (7 items). Participants responded to the items on a five-point Likert scale ranging from 0, "Not at all" to 4, "Very much." The total score ranges from 0 to 108; higher scores indicate a better patient-reported outcome/quality of life. Participants were asked to think back over the past week when responding to the items.

  8. Change From Baseline in the Functional Assessment of Cancer Therapy Lymphoma Trial Outcome Index (FACT-Lym TOI) Total Score During Treatment [Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months])]

    The FACT-Lym TOI is a measure that combines the FACT-Lym subscale (15 items; responses to each item range from 0, "Not at all" to 4, "Very much") with two domains taken from the FACT-G (responses to each item range from "Not at all " to "Very much"): Physical Well-being (7 items: lack of energy, nausea, meeting family needs, pain, side effects, feels ill, spends time in bed) and Functional Well-being (7 items: ability to work, work fulfilment, ability to enjoy life, illness acceptance, ability to sleep well, enjoying things done for fun, satisfaction with quality of life). This index is designed to be sensitive to changes in treatment regimens. The total FACT-Lym TOI score ranges from 0 to 116; higher scores indicate a better patient-reported outcome/quality of life. Participants were asked to think back over the past week when responding to the items.

  9. Time to Neutrophil and Platelet Recovery After Each Cycle of Salvage Chemotherapy [From the start of each cycle for a maximum of 5 weeks per cycle (assessed during treatment period of Baseline up to approximately 3 months)]

    Neutrophil (absolute neutrophil count [ANC]) recovery is defined as ANC >=0.5*10^9/Liter and increasing, and platelet (PLT) recovery is defined as PLT >=10*10^9/Liter and increasing. For each cycle, time to ANC recovery is defined as the time from the first dose to the first ANC >=0.5*10^9/Liter and increasing after the nadir in the cycle. For each cycle, time to PLT recovery is defined as the time from the first dose to the first PLT >=10*10^9/L and increasing after the nadir in the cycle.

  10. Time to Engraftment After High-dose Therapy (HDT)/ASCT [From ASCT up to 42 days post-ASCT (Baseline up to approximately 4.5 months)]

    Engraftment is defined as 1) three consecutive days when the ANC is ≥0.5x109/L and 2) an unsupported platelet count of ≥20x109/L, and the engraftment date is the date that this occurs. If engraftment was not achieved by Day 42 or the last observation, engraftment was deemed to be a failure, and censoring took place at Day 42 or at the last observation.

Eligibility Criteria

Criteria

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

  • Subjects with CD20 positive DLBCL or grade 3b follicular lymphoma (FL) at original diagnosis.

  • Refractory to, or relapsed following, first-line treatment with rituximab combined with anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.

  • CT with involvement of 2 or more clearly demarcated lesions/ nodes with a long axis > 1.5 cm and short axis >= 1.0cm or 1 clearly demarcated lesion/ node with a long axis > 2.0 cm and short axis >= 1.0 cm.

  • Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites.

  • Age 18 yrs or older.

  • ECOG performance status of 0, 1 or 2.

  • Eligible for high dose chemotherapy and ASCT.

  • Resolution of toxicities from first-line therapy to a grade that in the opinion of the investigator does not contraindicate study participation.

  • Signed written informed consent.

Exclusion Criteria:

  • Previous cancer therapy for lymphoma, with the exception of first-line rituximab/ anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to or combined with first-line chemotherapy, as maintenance therapy, and radiotherapy in a limited field or as a part of the first-line treatment plan.

  • Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to start of study therapy.

  • Planned post-randomization chronic glucocorticoid use (limited acute use is allowed and defined by the protocol) unless administered as therapy for mild COPD or asthma.

  • Clinically significant cardiac disease, active or chronic infections, serious significant diseases, other cancer within last 5 years. History of significant cerebrovascular disease.

  • Prior treatment with anti-CD20 monoclonal antibodies with the exception of rituximab.

  • Abnormal/ inadequate WBC count, liver, and kidney function.

  • Pregnant or lactating women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception during and up to 1 year following dosing completion.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Sacramento California United States 95816
2 GSK Investigational Site New Haven Connecticut United States 06520
3 GSK Investigational Site Chicago Illinois United States 60612-7323
4 GSK Investigational Site Chicago Illinois United States 60637
5 GSK Investigational Site Westwood Kansas United States 66205
6 GSK Investigational Site Jackson Mississippi United States 39216-4505
7 GSK Investigational Site New York New York United States 10065
8 GSK Investigational Site Syracuse New York United States 13210
9 GSK Investigational Site Chaple Hill North Carolina United States 27599-7305
10 GSK Investigational Site Philadelphia Pennsylvania United States 19140
11 GSK Investigational Site Providence Rhode Island United States 02908
12 GSK Investigational Site Charleston South Carolina United States 29425
13 GSK Investigational Site Greenville South Carolina United States 29601
14 GSK Investigational Site Nashville Tennessee United States 37203
15 GSK Investigational Site San Antonio Texas United States 78229
16 GSK Investigational Site Seattle Washington United States 98108
17 GSK Investigational Site Capital Federal Buenos Aires Argentina C1426ANZ
18 GSK Investigational Site Ciudad Autonoma de Buenos Aires Buenos Aires Argentina C1431FWO
19 GSK Investigational Site La Plata Buenos Aires Argentina B1900AXI
20 GSK Investigational Site Graz Austria 8036
21 GSK Investigational Site Innsbruck Austria 6020
22 GSK Investigational Site Linz Austria 4020
23 GSK Investigational Site Linz Austria 4021
24 GSK Investigational Site Salzburg Austria A-5020
25 GSK Investigational Site Wien Austria 1090
26 GSK Investigational Site Wien Austria 1140
27 GSK Investigational Site Brugge Belgium 8000
28 GSK Investigational Site Bruxelles Belgium 1200
29 GSK Investigational Site Gent Belgium 9000
30 GSK Investigational Site Hasselt Belgium 3500
31 GSK Investigational Site Leuven Belgium 3000
32 GSK Investigational Site Yvoir Belgium 5530
33 GSK Investigational Site Fuzhou Fujian China 350014
34 GSK Investigational Site Guangzhou Guangdong China 510060
35 GSK Investigational Site Guangzhou Guangdong China 510080
36 GSK Investigational Site Guangzhou Guangdong China 510515
37 GSK Investigational Site Nanjing Jiangsu China 210029
38 GSK Investigational Site Jianan Shandong China 250012
39 GSK Investigational Site Hangzhou Zhejiang China 310003
40 GSK Investigational Site Beijing China 100021
41 GSK Investigational Site Beijing China 100044
42 GSK Investigational Site Beijing China 100071
43 GSK Investigational Site Beijing China 100142
44 GSK Investigational Site Beijing China 100191
45 GSK Investigational Site Beijing China 100730
46 GSK Investigational Site Beijing China 100853
47 GSK Investigational Site Chengdu China 610041
48 GSK Investigational Site Jiang Su Province China 215006
49 GSK Investigational Site Shanghai China 200025
50 GSK Investigational Site Shanghai China 200032
51 GSK Investigational Site Tianjin China 300020
52 GSK Investigational Site Brno Czech Republic 625 00
53 GSK Investigational Site Hradec Kralove Czech Republic
54 GSK Investigational Site Aarhus Denmark 8000 C
55 GSK Investigational Site Koebenhavn Denmark 2100
56 GSK Investigational Site Tallinn Estonia 13419
57 GSK Investigational Site Tartu Estonia 51014
58 GSK Investigational Site Helsinki Finland 00029
59 GSK Investigational Site Oulu Finland 90029
60 GSK Investigational Site Tampere Finland 33520
61 GSK Investigational Site Ulm Baden-Wuerttemberg Germany 89081
62 GSK Investigational Site Aachen Nordrhein-Westfalen Germany 52074
63 GSK Investigational Site Muenster Nordrhein-Westfalen Germany 48149
64 GSK Investigational Site Berlin Germany 13353
65 GSK Investigational Site Athens Greece 11 527
66 GSK Investigational Site Athens Greece 11525
67 GSK Investigational Site Budapest Hungary 1097
68 GSK Investigational Site Budapest Hungary 1122
69 GSK Investigational Site Debrecen Hungary 4012
70 GSK Investigational Site Győr Hungary 9023
71 GSK Investigational Site Kaposvár Hungary 7400
72 GSK Investigational Site Szeged Hungary 6720
73 GSK Investigational Site Szombathely Hungary 9700
74 GSK Investigational Site Ludhiana India 141008
75 GSK Investigational Site Pune India 411001
76 GSK Investigational Site Vellore India 632004
77 GSK Investigational Site Dublin Ireland 4
78 GSK Investigational Site Galway Ireland
79 GSK Investigational Site James Street Ireland 8
80 GSK Investigational Site Petach-Tikva Israel 49100
81 GSK Investigational Site Ramat Gan Israel 52621
82 GSK Investigational Site Aichi Japan 466-8650
83 GSK Investigational Site Akita Japan 010-8543
84 GSK Investigational Site Fukuoka Japan 811-1395
85 GSK Investigational Site Hokkaido Japan 060-8648
86 GSK Investigational Site Hyogo Japan 650-0047
87 GSK Investigational Site Ibaraki Japan 305-8576
88 GSK Investigational Site Kanagawa Japan 236-0004
89 GSK Investigational Site Kanagawa Japan 259-1143
90 GSK Investigational Site Kyoto Japan 602-8566
91 GSK Investigational Site Miyagi Japan 980-8574
92 GSK Investigational Site Nagano Japan 390-8621
93 GSK Investigational Site Nagasaki Japan 852-8501
94 GSK Investigational Site Okayama Japan 700-8558
95 GSK Investigational Site Osaka Japan 589-8511
96 GSK Investigational Site Tochigi Japan 329-0498
97 GSK Investigational Site Tokushima Japan 770-8503
98 GSK Investigational Site Tokyo Japan 104-0045
99 GSK Investigational Site Tokyo Japan 113-8655
100 GSK Investigational Site Tokyo Japan 135-8550
101 GSK Investigational Site Tokyo Japan 162-8655
102 GSK Investigational Site Jellanamdo Korea, Republic of 519-809
103 GSK Investigational Site Seoul Korea, Republic of 120-752
104 GSK Investigational Site Seoul Korea, Republic of 135-710
105 GSK Investigational Site Amersfoort Netherlands 3818 ES
106 GSK Investigational Site Amsterdam Netherlands 1066 CX
107 GSK Investigational Site Amsterdam Netherlands 1081 HV
108 GSK Investigational Site Amsterdam Netherlands 1105 AZ
109 GSK Investigational Site Den Haag Netherlands 2545 CH
110 GSK Investigational Site Enschede Netherlands 7511JX
111 GSK Investigational Site Groningen Netherlands 9713 GZ
112 GSK Investigational Site Hoofddorp Netherlands 2134 TM
113 GSK Investigational Site Leiden Netherlands 2333 ZA
114 GSK Investigational Site Maastricht Netherlands 6229 HX
115 GSK Investigational Site Nieuwegein Netherlands 3435 CM
116 GSK Investigational Site Nijmegen Netherlands 6525 GA
117 GSK Investigational Site Rotterdam Netherlands 3015 CE
118 GSK Investigational Site Rotterdam Netherlands 3075 EA
119 GSK Investigational Site Rotterdam Netherlands 3079 DZ
120 GSK Investigational Site Sittard-geleen Netherlands 6162 BG
121 GSK Investigational Site Utrecht Netherlands 3584 CX
122 GSK Investigational Site Zwolle Netherlands 8025 AB
123 GSK Investigational Site Oslo Norway 0310
124 GSK Investigational Site Chorzow Poland 41-500
125 GSK Investigational Site Gdansk Poland 80-952
126 GSK Investigational Site Poznan Poland 60-833
127 GSK Investigational Site Warszawa Poland 02-776
128 GSK Investigational Site Warszawa Poland 02-781
129 GSK Investigational Site Wroclaw Poland 50-367
130 GSK Investigational Site Moscow Russian Federation 125101
131 GSK Investigational Site St-Petersburg Russian Federation 197110
132 GSK Investigational Site St. Petersburg Russian Federation 197022
133 GSK Investigational Site Singapore Singapore 119074
134 GSK Investigational Site Barcelona Spain 08041
135 GSK Investigational Site Madrid Spain 28006
136 GSK Investigational Site Madrid Spain 28007
137 GSK Investigational Site Madrid Spain 28008
138 GSK Investigational Site Madrid Spain 28041
139 GSK Investigational Site Majadahonda (Madrid) Spain 28222
140 GSK Investigational Site Murcia Spain 30120
141 GSK Investigational Site Pamplona Spain 31008
142 GSK Investigational Site Pozuelo de Alarcón/Madrid Spain 28223
143 GSK Investigational Site Salamanca Spain 37007
144 GSK Investigational Site Göteborg Sweden
145 GSK Investigational Site Lund Sweden SE-221 85
146 GSK Investigational Site Stockholm Sweden SE-141 86
147 GSK Investigational Site Uppsala Sweden SE-751 85
148 GSK Investigational Site Bangkok Thailand 10330
149 GSK Investigational Site Bangkok Thailand 10400
150 GSK Investigational Site Bangkok Thailand 10700
151 GSK Investigational Site Birmingham United Kingdom B15 2TH
152 GSK Investigational Site Blackpool United Kingdom FY3 8NR
153 GSK Investigational Site Bristol United Kingdom BS2 8ED
154 GSK Investigational Site Cambridge United Kingdom CB2 2XY
155 GSK Investigational Site Cheltenham United Kingdom GL53 7AN
156 GSK Investigational Site Edinburgh United Kingdom EH4 2XU
157 GSK Investigational Site Glasgow United Kingdom G12 0YN
158 GSK Investigational Site Headington, Oxford United Kingdom OX3 7LE
159 GSK Investigational Site Leeds United Kingdom LS9 7TF
160 GSK Investigational Site Liverpool United Kingdom L7 8XP
161 GSK Investigational Site London United Kingdom NW1 2PG
162 GSK Investigational Site London United Kingdom NW3 2QG
163 GSK Investigational Site London United Kingdom SE5 9RS
164 GSK Investigational Site London United Kingdom W12 0HS
165 GSK Investigational Site Manchester United Kingdom M13 9WL
166 GSK Investigational Site Manchester United Kingdom M20 4BX
167 GSK Investigational Site Newcastle upon Tyne United Kingdom NE7 7DN
168 GSK Investigational Site Northwood United Kingdom HA6 2RN
169 GSK Investigational Site Nottingham United Kingdom NG5 1PB
170 GSK Investigational Site Sheffield United Kingdom S10 2JF
171 GSK Investigational Site Southampton United Kingdom SO16 6YD
172 GSK Investigational Site Whitchurch, Cardiff United Kingdom CF14 2TL
173 GSK Investigational Site Wolverhampton United Kingdom WV10 OQP

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01014208
Other Study ID Numbers:
  • 110928
First Posted:
Nov 16, 2009
Last Update Posted:
Aug 7, 2015
Last Verified:
Feb 1, 2015
Keywords provided by GlaxoSmithKline
The All Ireland Cooperative Oncology Research Group
GELTAMO
National Cancer Research Institute Lymphoma Clinical Studies Group
Genmab
ofatumumab
Japan Clinical Oncology Group
Oncology
Polish Lymphoma Research Group
Salvage chemotherapy
refractory
HOVON
DVD
relapsed
safety
efficacy
DHAP
rituximab
Autologous Stem Cell Transplant
Dutch-Belgian Cooperative Trial Group for Hematology-Oncology
Grupo Espanol de Linfomas
Nordic Lymphoma Group
Additional relevant MeSH terms:
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Rituximab
Ofatumumab

Study Results

Participant Flow

Recruitment Details Participants who were refractory to, or had relapsed following, first-line treatment with rituximab in combination with an anthracycline- or anthracenedione-containing chemotherapy regimen, and who were eligible for autologous stem cell transplant (ASCT), were eligible for enrollment.
Pre-assignment Detail Eligible participants were randomized to receive either rituximab or ofatumumab in addition to salvage chemotherapy.
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Period Title: Overall Study
STARTED 225 222
Intent-to-Treat Population 223 222
COMPLETED 131 122
NOT COMPLETED 94 100

Baseline Characteristics

Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy Total
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Total of all reporting groups
Overall Participants 223 222 445
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
53.4
(12.22)
55.2
(10.80)
54.3
(11.55)
Sex: Female, Male (Count of Participants)
Female
88
39.5%
85
38.3%
173
38.9%
Male
135
60.5%
137
61.7%
272
61.1%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage
4
1.8%
4
1.8%
8
1.8%
American Indian or Alaska Native
0
0%
1
0.5%
1
0.2%
Asian - Central/South Asian Heritage
3
1.3%
4
1.8%
7
1.6%
Asian - East Asian Heritage
24
10.8%
31
14%
55
12.4%
Asian - Japanese Heritage
19
8.5%
22
9.9%
41
9.2%
Asian - South East Asian Heritage
4
1.8%
4
1.8%
8
1.8%
Asian - Mixed Race
0
0%
1
0.5%
1
0.2%
White - Arabic/North African Heritage
1
0.4%
1
0.5%
2
0.4%
White - White/Caucasian/European Heritage
168
75.3%
151
68%
319
71.7%
Missing
0
0%
3
1.4%
3
0.7%
Number of participants with the indicated SaaIPI scores (Number) [Number]
0 or 1
136
61%
133
59.9%
269
60.4%
2 or 3
87
39%
89
40.1%
176
39.6%
Number of participants in the indicated categories per best response to first-line treatment (Number) [Number]
Late relapsers
66
29.6%
63
28.4%
129
29%
Early relapsers/Refractory
157
70.4%
159
71.6%
316
71%

Outcome Measures

1. Primary Outcome
Title Progression-free Survival as Assessed by Independent Reviewers
Description Progression-free survival is defined as the interval of time from the randomization date until the date of stable disease (SD; failure to attain the criteria needed for a CR or PR and no fulfillment of the criteria for progressive disease [PD]) after two cycles of salvage chemotherapy, progression, or death, whichever occurs first. Disease progression was based on the assessments of independent reviewers for the disease under study. Disease progression was based on imaging data via the Revised Response Criteria for Malignant Lymphoma (RRCML).
Time Frame From randomization until the date of stable disease after two cycles of salvage chemotherapy, progression, or death (assessed for up to 5 years)

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) Population: all participants who were randomized and commenced study therapy (at least one dose of a study drug)
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Measure Participants 223 222
Median (95% Confidence Interval) [Months]
2.14
1.81
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.333
Comments p-value from stratified log-rank test are adjusted for stratification factors.
Method Stratified Log-rank test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.89 to 1.42
Parameter Dispersion Type:
Value:
Estimation Comments The Pike estimator was the statistical method used to estimate the hazard ratio.
2. Secondary Outcome
Title Number of Participants With Overall Response (OR) and Complete Response (CR) After Salvage Chemoimmunotherapy
Description OR is defined as the number of participants achieving either a complete response (CR) or a partial response (PR). CR is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR is defined as at least a 50% decrease from Baseline in the sum of the product of the diameters of target lesions. RRCML was used to assess CR and PR.
Time Frame At completion of up to 3 cycles of salvage chemoimmunotherapy (assessed up to 9 weeks)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Measure Participants 223 222
Independent reviewer-assessed OR
94
42.2%
84
37.8%
Independent reviewer-assessed CR
48
21.5%
34
15.3%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4053
Comments p-value for the test of Odds Ratio being 1.
Method Cochran-Mantel-Haenszel
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.56 to 1.24
Parameter Dispersion Type:
Value:
Estimation Comments For Category title- Independent reviewer-assessed OR
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1167
Comments p-value for the test of Odds Ratio being 1.
Method Cochran-Mantel-Haenszel
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.39 to 1.10
Parameter Dispersion Type:
Value:
Estimation Comments For Category title- Independent reviewer-assessed CR
3. Secondary Outcome
Title Number of Participants With Overall Response (OR) and Complete Response (CR) Three Months After Autologous Stem Cell Transplant
Description OR is defined as the number of participants achieving either a complete response (CR) or a partial response (PR). CR is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR is defined as at least a 50% decrease from Baseline in the sum of the product of the diameters of target lesions. RRCML was used to assess CR and PR.
Time Frame At 3 months after completion of autologous stem cell transplantation (ASCT) (assessed up to 6 months)

Outcome Measure Data

Analysis Population Description
ITT Population. Only participants completing HDT/ASCT are included.
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Measure Participants 83 74
Independent reviewer-assessed OR
57
25.6%
53
23.9%
Independent reviewer-assessed CR
44
19.7%
43
19.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8209
Comments p-value for the test of Odds Ratio being 1.
Method Cochran-Mantel-Haenszel
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.55 to 2.43
Parameter Dispersion Type:
Value:
Estimation Comments For Category title- Independent reviewer-assessed OR
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6313
Comments p-value for the test of Odds Ratio being 1.
Method Cochran-Mantel-Haenszel
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.62 to 2.43
Parameter Dispersion Type:
Value:
Estimation Comments For Category title- Independent reviewer-assessed CR
4. Secondary Outcome
Title Event-free Survival
Description Event-free survival is defined as the time from randomization to progressive disease (PD; disease whose course is growth, or spread of the disease), stable disease (SD; failure to attain the criteria needed for a CR or PR and no fulfillment of the criteria for PD) after completion of 2 cycles of therapy, commencement of a new treatment for diffuse large B cell lymphoma (DLBCL) (e.g., radiotherapy), or death from any cause, whichever occurs first. Disease progression was based on the assessments of independent reviewers for the disease under study. Disease progression was based on imaging data via the Revised Response Criteria for Malignant Lymphoma (RRCML).
Time Frame From randomization to progressive disease, stable disease after completion of 2 cycles of therapy, commencement of a new treatment for DLBCL, or death due to any cause (assessed for up to 5 years)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Measure Participants 223 222
Median (95% Confidence Interval) [Months]
1.84
1.74
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.346
Comments p-value from stratified log-rank test are adjusted for stratification factors.
Method Stratified log-rank test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.90 to 1.36
Parameter Dispersion Type:
Value:
Estimation Comments Confidence Interval estimated using the Brookmeyer-Crowley method. HR are estimated using Pike estimator. A hazard ratio <1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.
5. Secondary Outcome
Title Overall Survival (OS)
Description OS is defined as the time from randomization to death due to any cause. Participants who were still alive by the end of the study were censored.
Time Frame From randomization to death due to any cause (assessed for up to 5 years)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Measure Participants 223 222
Median (95% Confidence Interval) [Months]
13.17
13.86
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.377
Comments p-value from stratified log-rank test are adjusted for stratification factors.
Method Stratified log-rank test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.70 to 1.15
Parameter Dispersion Type:
Value:
Estimation Comments Confidence Interval estimated using the Brookmeyer-Crowley method. HR are estimated using Pike estimator. A hazard ratio <1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.
6. Secondary Outcome
Title Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram From Peripheral Blood
Description Stem cell mobilization is the process of stimulating the hematopoietic stem cells (CD34+) to move out of the bone marrow and into the bloodstream, where they can be collected via a process called apheresis. Successful mobilization is defined as the collection of >2*10^6 CD34+ cells/kg. Only those participants, who commenced harvest, following the administration of rituximab or ofatumumab in combination with DHAP combination chemotherapy, were assessed. The number of participants with adequate harvest of CD34+ stem cells (at least 2*10^6 CD34+ cells/kg) after dosing of salvage therapy in Cycle 2 and Cycle 3 was analyzed.
Time Frame During Cycles 2 and/or 3 (Weeks 4-9)

Outcome Measure Data

Analysis Population Description
ITT Population. Only participants commencing leukapheresis are included.
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Measure Participants 134 125
Number [Participants]
121
54.3%
120
54.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1161
Comments p-value for the test of Odds Ratio being 1.
Method Cochran-Mantel-Haenszel
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.57
Confidence Interval (2-Sided) 95%
0.83 to 9.50
Parameter Dispersion Type:
Value:
Estimation Comments
7. Secondary Outcome
Title Number of Participants Completing Autologous Stem Cell Transplant (ASCT)
Description The number of participants who completed ASCT is reported.
Time Frame Approximately 4 to 6 weeks following Cycle 3 (assessed up to 3 months)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Measure Participants 223 222
Number [Participants]
83
37.2%
74
33.3%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4481
Comments p-value for the test of Odds Ratio being 1.
Method Cochran-Mantel-Haenszel
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.56 to 1.27
Parameter Dispersion Type:
Value:
Estimation Comments Statistics are presented for Completion rate
8. Secondary Outcome
Title Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) During Treatment
Description The FACT-G was developed by the Functional Assessment of Chronic Illness Therapy (FACIT) group for use in adults in a wide range of oncology clinical trial populations. The 27 items of the FACT-G are scored in the following domains: Physical Well-being (7 items), Social/Family Wellbeing (7 items), Emotional Well-being (6 items), and Functional Well-being (7 items). Participants responded to the items on a five-point Likert scale ranging from 0, "Not at all" to 4, "Very much." The total score ranges from 0 to 108; higher scores indicate a better patient-reported outcome/quality of life. Participants were asked to think back over the past week when responding to the items.
Time Frame Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months])

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants who provided data were assessed.
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Measure Participants 172 175
Mean (Standard Error) [scores on a scale]
-2.561
(0.7671)
-2.591
(0.7696)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.978
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.030
Confidence Interval (2-Sided) 95%
-2.110 to 2.170
Parameter Dispersion Type:
Value:
Estimation Comments
9. Secondary Outcome
Title Change From Baseline in the Functional Assessment of Cancer Therapy Lymphoma Trial Outcome Index (FACT-Lym TOI) Total Score During Treatment
Description The FACT-Lym TOI is a measure that combines the FACT-Lym subscale (15 items; responses to each item range from 0, "Not at all" to 4, "Very much") with two domains taken from the FACT-G (responses to each item range from "Not at all " to "Very much"): Physical Well-being (7 items: lack of energy, nausea, meeting family needs, pain, side effects, feels ill, spends time in bed) and Functional Well-being (7 items: ability to work, work fulfilment, ability to enjoy life, illness acceptance, ability to sleep well, enjoying things done for fun, satisfaction with quality of life). This index is designed to be sensitive to changes in treatment regimens. The total FACT-Lym TOI score ranges from 0 to 116; higher scores indicate a better patient-reported outcome/quality of life. Participants were asked to think back over the past week when responding to the items.
Time Frame Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months])

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants who provided data were assessed.
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Measure Participants 172 174
Mean (Standard Error) [scores on a scale]
-2.028
(0.9196)
-3.156
(0.9204)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.387
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.129
Confidence Interval (2-Sided) 95%
-1.434 to 3.691
Parameter Dispersion Type:
Value:
Estimation Comments
10. Secondary Outcome
Title Time to Neutrophil and Platelet Recovery After Each Cycle of Salvage Chemotherapy
Description Neutrophil (absolute neutrophil count [ANC]) recovery is defined as ANC >=0.5*10^9/Liter and increasing, and platelet (PLT) recovery is defined as PLT >=10*10^9/Liter and increasing. For each cycle, time to ANC recovery is defined as the time from the first dose to the first ANC >=0.5*10^9/Liter and increasing after the nadir in the cycle. For each cycle, time to PLT recovery is defined as the time from the first dose to the first PLT >=10*10^9/L and increasing after the nadir in the cycle.
Time Frame From the start of each cycle for a maximum of 5 weeks per cycle (assessed during treatment period of Baseline up to approximately 3 months)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available for analysis in the given cycle were assessed.
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Measure Participants 223 222
Neutrophils, Cycle 1, n=223, 222
8.0
11.0
Neutrophils, Cycle 2, n=196, 199
8.0
11.0
Neutrophils, Cycle 3, n=137, 129
10.0
7.0
Platelets, Cycle 1, n=223, 222
13.0
12.0
Platelets, Cycle 2, n=196, 199
13.0
13.0
Platelets, Cycle 3, n=137, 129
13.0
13.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments Statistics are presented for Category-Neutrophils, Cycle 1. Confidence Interval (CI) estimated using the Brookmeyer-Crowley method. HR are estimated using the Pike estimator. A hazard ratio <1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.479
Comments p-value from stratified log-rank test are adjusted for stratification factors.
Method Stratified Log-Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.74 to 1.16
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments Statistics are presented for Category-Neutrophils, Cycle 2. Confidence Interval (CI) estimated using the Brookmeyer-Crowley method. HR are estimated using the Pike estimator. A hazard ratio <1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.059
Comments p-value from stratified log-rank test are adjusted for stratification factors.
Method Stratified Log-Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.64 to 1.02
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments Statistics are presented for Category-Neutrophils, Cycle 3. Confidence Interval (CI) estimated using the Brookmeyer-Crowley method. HR are estimated using the Pike estimator. A hazard ratio <1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.451
Comments p-value from stratified log-rank test are adjusted for stratification factors.
Method Stratified Log-Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.83 to 1.48
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments Statistics are presented for Category-Platelets, Cycle 1. Confidence Interval (CI) estimated using the Brookmeyer-Crowley method. HR are estimated using the Pike estimator. A hazard ratio <1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.597
Comments p-value from stratified log-rank test are adjusted for stratification factors.
Method Stratified Log-Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.86 to 1.29
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments Statistics are presented for Category-Platelets, Cycle 2. Confidence Interval (CI) estimated using the Brookmeyer-Crowley method. HR are estimated using the Pike estimator. A hazard ratio <1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.199
Comments p-value from stratified log-rank test are adjusted for stratification factors.
Method Stratified Log-Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.70 to 1.10
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments Statistics are presented for Category-Platelets, Cycle 3. Confidence Interval (CI) estimated using the Brookmeyer-Crowley method. HR are estimated using the Pike estimator. A hazard ratio <1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.102
Comments p-value from stratified log-rank test are adjusted for stratification factors.
Method Stratified Log-Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
0.93 to 1.59
Parameter Dispersion Type:
Value:
Estimation Comments
11. Secondary Outcome
Title Time to Engraftment After High-dose Therapy (HDT)/ASCT
Description Engraftment is defined as 1) three consecutive days when the ANC is ≥0.5x109/L and 2) an unsupported platelet count of ≥20x109/L, and the engraftment date is the date that this occurs. If engraftment was not achieved by Day 42 or the last observation, engraftment was deemed to be a failure, and censoring took place at Day 42 or at the last observation.
Time Frame From ASCT up to 42 days post-ASCT (Baseline up to approximately 4.5 months)

Outcome Measure Data

Analysis Population Description
Safety population. Only participants completing HDT/ASCT are included.
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Measure Participants 83 74
Median (95% Confidence Interval) [Days]
24.0
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + Chemotherapy, Ofatumumab + Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.035
Comments p-value from stratified log-rank test are adjusted for stratification factors.
Method Stratified Log-Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.36 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments Confidence Interval estimated using the Brookmeyer-Crowley method. HR are estimated using Pike estimator. A hazard ratio <1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.

Adverse Events

Time Frame Adverse events (AEs) were collected up to 60 days after the last dose of study treatment, or the commencement of high-dose chemotherapy, or anti-cancer therapy, whichever occurred first (up to approximately 16 study weeks).
Adverse Event Reporting Description Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of study drug.
Arm/Group Title Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Arm/Group Description Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5). Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
All Cause Mortality
Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN)
Serious Adverse Events
Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 115/223 (51.6%) 118/222 (53.2%)
Blood and lymphatic system disorders
Febrile neutropenia 30/223 (13.5%) 28/222 (12.6%)
Thrombocytopenia 11/223 (4.9%) 12/222 (5.4%)
Neutropenia 7/223 (3.1%) 6/222 (2.7%)
Pancytopenia 1/223 (0.4%) 5/222 (2.3%)
Anaemia 3/223 (1.3%) 0/222 (0%)
Leukopenia 2/223 (0.9%) 0/222 (0%)
Bone marrow failure 1/223 (0.4%) 0/222 (0%)
Cardiac disorders
Atrial fibrillation 1/223 (0.4%) 2/222 (0.9%)
Acute coronary syndrome 1/223 (0.4%) 1/222 (0.5%)
Angina pectoris 0/223 (0%) 1/222 (0.5%)
Atrial flutter 1/223 (0.4%) 0/222 (0%)
Cardiac arrest 0/223 (0%) 1/222 (0.5%)
Cardiac failure 0/223 (0%) 1/222 (0.5%)
Left ventricular failure 1/223 (0.4%) 0/222 (0%)
Myocardial infarction 0/223 (0%) 1/222 (0.5%)
Pericarditis 1/223 (0.4%) 0/222 (0%)
Sinus bradycardia 1/223 (0.4%) 0/222 (0%)
Supraventricular tachycardia 1/223 (0.4%) 0/222 (0%)
Tachyarrhythmia 0/223 (0%) 1/222 (0.5%)
Ear and labyrinth disorders
Deafness 1/223 (0.4%) 0/222 (0%)
Tinnitus 1/223 (0.4%) 0/222 (0%)
Eye disorders
Blindness 1/223 (0.4%) 0/222 (0%)
Conjunctivitis 1/223 (0.4%) 0/222 (0%)
Eyelid function disorder 0/223 (0%) 1/222 (0.5%)
Ocular hypertension 1/223 (0.4%) 0/222 (0%)
Periorbital oedema 0/223 (0%) 1/222 (0.5%)
Vision blurred 0/223 (0%) 1/222 (0.5%)
Vitreous haemorrhage 1/223 (0.4%) 0/222 (0%)
Gastrointestinal disorders
Vomiting 13/223 (5.8%) 10/222 (4.5%)
Nausea 9/223 (4%) 4/222 (1.8%)
Diarrhoea 1/223 (0.4%) 5/222 (2.3%)
Gastrointestinal haemorrhage 2/223 (0.9%) 2/222 (0.9%)
Abdominal pain 1/223 (0.4%) 1/222 (0.5%)
Abdominal pain upper 2/223 (0.9%) 0/222 (0%)
Constipation 2/223 (0.9%) 0/222 (0%)
Stomatitis 0/223 (0%) 2/222 (0.9%)
Ascites 1/223 (0.4%) 0/222 (0%)
Colitis 1/223 (0.4%) 0/222 (0%)
Dental caries 0/223 (0%) 1/222 (0.5%)
Duodenal ulcer 0/223 (0%) 1/222 (0.5%)
Gastric haemorrhage 1/223 (0.4%) 0/222 (0%)
Gastrointestinal inflammation 0/223 (0%) 1/222 (0.5%)
Ileal stenosis 1/223 (0.4%) 0/222 (0%)
Lower gastrointestinal haemorrhage 0/223 (0%) 1/222 (0.5%)
Melaena 0/223 (0%) 1/222 (0.5%)
Oesophageal varices haemorrhage 1/223 (0.4%) 0/222 (0%)
Upper gastrointestinal haemorrhage 1/223 (0.4%) 0/222 (0%)
General disorders
Pyrexia 11/223 (4.9%) 8/222 (3.6%)
Mucosal inflammation 2/223 (0.9%) 3/222 (1.4%)
Fatigue 0/223 (0%) 3/222 (1.4%)
General physical health deterioration 1/223 (0.4%) 2/222 (0.9%)
Chest pain 0/223 (0%) 2/222 (0.9%)
Chills 0/223 (0%) 1/222 (0.5%)
Pain 1/223 (0.4%) 0/222 (0%)
Euthanasia 0/223 (0%) 1/222 (0.5%)
Hepatobiliary disorders
Cholecystitis acute 1/223 (0.4%) 0/222 (0%)
Hepatic failure 0/223 (0%) 1/222 (0.5%)
Immune system disorders
Anaphylactic reaction 0/223 (0%) 1/222 (0.5%)
Hypersensitivity 0/223 (0%) 1/222 (0.5%)
Secondary immunodeficiency 1/223 (0.4%) 0/222 (0%)
Infections and infestations
Sepsis 9/223 (4%) 4/222 (1.8%)
Neutropenic sepsis 4/223 (1.8%) 8/222 (3.6%)
Pneumonia 2/223 (0.9%) 4/222 (1.8%)
Device related infection 3/223 (1.3%) 2/222 (0.9%)
Septic shock 4/223 (1.8%) 2/222 (0.9%)
Infection 0/223 (0%) 4/222 (1.8%)
Urinary tract infection 2/223 (0.9%) 1/222 (0.5%)
Influenza 1/223 (0.4%) 1/222 (0.5%)
Lung infection 1/223 (0.4%) 1/222 (0.5%)
Pneumonia cytomegaloviral 0/223 (0%) 2/222 (0.9%)
Pulmonary mycosis 1/223 (0.4%) 1/222 (0.5%)
Sinusitis 2/223 (0.9%) 0/222 (0%)
Abscess 1/223 (0.4%) 0/222 (0%)
Bacteraemia 0/223 (0%) 1/222 (0.5%)
Bronchopulmonary aspergillosis 1/223 (0.4%) 0/222 (0%)
Cellulitis 1/223 (0.4%) 0/222 (0%)
Clostridial infection 1/223 (0.4%) 0/222 (0%)
Clostridium difficile colitis 0/223 (0%) 1/222 (0.5%)
Device related sepsis 1/223 (0.4%) 0/222 (0%)
Diarrhoea infectious 0/223 (0%) 1/222 (0.5%)
Escherichia bacteraemia 0/223 (0%) 1/222 (0.5%)
Fungal endocarditis 1/223 (0.4%) 0/222 (0%)
Gastrointestinal candidiasis 1/223 (0.4%) 0/222 (0%)
Gastrointestinal infection 1/223 (0.4%) 0/222 (0%)
Herpes simplex 0/223 (0%) 1/222 (0.5%)
Neutropenic infection 0/223 (0%) 1/222 (0.5%)
Parainfluenzae virus infection 1/223 (0.4%) 0/222 (0%)
Pneumonia klebsiella 1/223 (0.4%) 0/222 (0%)
Post procedural sepsis 0/223 (0%) 1/222 (0.5%)
Postoperative wound infection 1/223 (0.4%) 0/222 (0%)
Rhinovirus infection 1/223 (0.4%) 0/222 (0%)
Skin infection 1/223 (0.4%) 0/222 (0%)
Staphylococcal bacteraemia 0/223 (0%) 1/222 (0.5%)
Staphylococcal skin infection 1/223 (0.4%) 0/222 (0%)
Viral infection 1/223 (0.4%) 0/222 (0%)
Wound infection 0/223 (0%) 1/222 (0.5%)
Herpes zoster 1/223 (0.4%) 0/222 (0%)
Meningitis bacterial 0/223 (0%) 1/222 (0.5%)
Injury, poisoning and procedural complications
Spinal compression fracture 1/223 (0.4%) 1/222 (0.5%)
Contusion 0/223 (0%) 1/222 (0.5%)
Facial bones fracture 1/223 (0.4%) 0/222 (0%)
Humerus fracture 1/223 (0.4%) 0/222 (0%)
Infusion related reaction 0/223 (0%) 1/222 (0.5%)
Investigations
Blood creatinine increased 5/223 (2.2%) 12/222 (5.4%)
Platelet count decreased 2/223 (0.9%) 7/222 (3.2%)
Neutrophil count decreased 1/223 (0.4%) 3/222 (1.4%)
Alanine aminotransferase increased 0/223 (0%) 2/222 (0.9%)
White blood cell count decreased 0/223 (0%) 2/222 (0.9%)
Aspartate aminotransferase increased 0/223 (0%) 1/222 (0.5%)
Blood bilirubin increased 0/223 (0%) 1/222 (0.5%)
Blood potassium decreased 1/223 (0.4%) 0/222 (0%)
Blood urea increased 1/223 (0.4%) 0/222 (0%)
C-reactive protein increased 1/223 (0.4%) 0/222 (0%)
Creatinine renal clearance decreased 1/223 (0.4%) 0/222 (0%)
Electrocardiogram change 0/223 (0%) 1/222 (0.5%)
Weight increased 1/223 (0.4%) 0/222 (0%)
Metabolism and nutrition disorders
Dehydration 4/223 (1.8%) 3/222 (1.4%)
Hypokalaemia 3/223 (1.3%) 4/222 (1.8%)
Hyponatraemia 1/223 (0.4%) 4/222 (1.8%)
Tumour lysis syndrome 2/223 (0.9%) 3/222 (1.4%)
Hyperglycaemia 1/223 (0.4%) 1/222 (0.5%)
Hypomagnesaemia 1/223 (0.4%) 1/222 (0.5%)
Decreased appetite 0/223 (0%) 1/222 (0.5%)
Diabetes mellitus 0/223 (0%) 1/222 (0.5%)
Fluid overload 1/223 (0.4%) 0/222 (0%)
Hyperlipidaemia 0/223 (0%) 1/222 (0.5%)
Lactic acidosis 0/223 (0%) 1/222 (0.5%)
Musculoskeletal and connective tissue disorders
Back pain 0/223 (0%) 1/222 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer 0/223 (0%) 1/222 (0.5%)
Myelodysplastic syndrome 1/223 (0.4%) 1/222 (0.5%)
Lymphoma 1/223 (0.4%) 0/222 (0%)
Nervous system disorders
Syncope 1/223 (0.4%) 6/222 (2.7%)
Encephalopathy 1/223 (0.4%) 2/222 (0.9%)
Subarachnoid haemorrhage 1/223 (0.4%) 2/222 (0.9%)
Haemorrhage intracranial 1/223 (0.4%) 1/222 (0.5%)
Headache 1/223 (0.4%) 1/222 (0.5%)
VIIth nerve paralysis 1/223 (0.4%) 1/222 (0.5%)
Cerebral haemorrhage 0/223 (0%) 1/222 (0.5%)
Cerebral infarction 1/223 (0.4%) 0/222 (0%)
Cerebrovascular accident 0/223 (0%) 1/222 (0.5%)
Dizziness 0/223 (0%) 1/222 (0.5%)
Epilepsy 1/223 (0.4%) 0/222 (0%)
Peripheral motor neuropathy 1/223 (0.4%) 0/222 (0%)
Presyncope 0/223 (0%) 1/222 (0.5%)
Somnolence 0/223 (0%) 1/222 (0.5%)
Brachial plexopathy 1/223 (0.4%) 0/222 (0%)
Psychiatric disorders
Confusional state 0/223 (0%) 2/222 (0.9%)
Completed suicide 1/223 (0.4%) 0/222 (0%)
Renal and urinary disorders
Renal failure acute 12/223 (5.4%) 11/222 (5%)
Renal failure 3/223 (1.3%) 6/222 (2.7%)
Renal impairment 5/223 (2.2%) 2/222 (0.9%)
Renal injury 0/223 (0%) 2/222 (0.9%)
Haematuria 1/223 (0.4%) 0/222 (0%)
Nephropathy toxic 1/223 (0.4%) 0/222 (0%)
Renal failure chronic 0/223 (0%) 1/222 (0.5%)
Reproductive system and breast disorders
Epididymitis 2/223 (0.9%) 0/222 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion 1/223 (0.4%) 2/222 (0.9%)
Pulmonary embolism 2/223 (0.9%) 1/222 (0.5%)
Epistaxis 1/223 (0.4%) 1/222 (0.5%)
Hypoxia 1/223 (0.4%) 1/222 (0.5%)
Pulmonary oedema 0/223 (0%) 2/222 (0.9%)
Cough 0/223 (0%) 1/222 (0.5%)
Dyspnoea 0/223 (0%) 1/222 (0.5%)
Lung disorder 0/223 (0%) 1/222 (0.5%)
Pneumonitis 0/223 (0%) 1/222 (0.5%)
Pneumothorax 1/223 (0.4%) 0/222 (0%)
Pneumothorax spontaneous 1/223 (0.4%) 0/222 (0%)
Respiratory failure 1/223 (0.4%) 0/222 (0%)
Skin and subcutaneous tissue disorders
Rash 1/223 (0.4%) 1/222 (0.5%)
Hyperhidrosis 0/223 (0%) 1/222 (0.5%)
Rash maculo-papular 1/223 (0.4%) 0/222 (0%)
Swelling face 0/223 (0%) 1/222 (0.5%)
Urticaria 0/223 (0%) 1/222 (0.5%)
Vascular disorders
Hypotension 1/223 (0.4%) 3/222 (1.4%)
Orthostatic hypotension 0/223 (0%) 2/222 (0.9%)
Thrombosis 1/223 (0.4%) 1/222 (0.5%)
Deep vein thrombosis 0/223 (0%) 1/222 (0.5%)
Hypertension 0/223 (0%) 1/222 (0.5%)
Ischaemia 1/223 (0.4%) 0/222 (0%)
Vena cava thrombosis 0/223 (0%) 1/222 (0.5%)
Other (Not Including Serious) Adverse Events
Rituximab + Chemotherapy Ofatumumab + Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 217/223 (97.3%) 215/222 (96.8%)
Blood and lymphatic system disorders
Anaemia 136/223 (61%) 125/222 (56.3%)
Thrombocytopenia 109/223 (48.9%) 103/222 (46.4%)
Neutropenia 71/223 (31.8%) 67/222 (30.2%)
Leukopenia 25/223 (11.2%) 24/222 (10.8%)
Febrile neutropenia 24/223 (10.8%) 21/222 (9.5%)
Ear and labyrinth disorders
Tinnitus 21/223 (9.4%) 14/222 (6.3%)
Gastrointestinal disorders
Nausea 136/223 (61%) 129/222 (58.1%)
Vomiting 81/223 (36.3%) 68/222 (30.6%)
Constipation 65/223 (29.1%) 76/222 (34.2%)
Diarrhoea 70/223 (31.4%) 50/222 (22.5%)
Dyspepsia 24/223 (10.8%) 16/222 (7.2%)
Abdominal pain 19/223 (8.5%) 17/222 (7.7%)
Abdominal pain upper 14/223 (6.3%) 12/222 (5.4%)
Stomatitis 11/223 (4.9%) 12/222 (5.4%)
General disorders
Fatigue 80/223 (35.9%) 74/222 (33.3%)
Pyrexia 69/223 (30.9%) 60/222 (27%)
Oedema peripheral 30/223 (13.5%) 31/222 (14%)
Oedema 21/223 (9.4%) 24/222 (10.8%)
Mucosal inflammation 28/223 (12.6%) 11/222 (5%)
Chills 24/223 (10.8%) 13/222 (5.9%)
Malaise 17/223 (7.6%) 9/222 (4.1%)
Injury, poisoning and procedural complications
Infusion related reaction 2/223 (0.9%) 13/222 (5.9%)
Investigations
Platelet count decreased 63/223 (28.3%) 64/222 (28.8%)
Blood creatinine increased 31/223 (13.9%) 45/222 (20.3%)
White blood cell count decreased 25/223 (11.2%) 33/222 (14.9%)
Neutrophil count decreased 21/223 (9.4%) 34/222 (15.3%)
Weight increased 22/223 (9.9%) 22/222 (9.9%)
Haemoglobin decreased 18/223 (8.1%) 21/222 (9.5%)
Aspartate aminotransferase increased 20/223 (9%) 17/222 (7.7%)
Alanine aminotransferase increased 19/223 (8.5%) 15/222 (6.8%)
Weight decreased 11/223 (4.9%) 23/222 (10.4%)
Blood potassium decreased 8/223 (3.6%) 13/222 (5.9%)
Blood lactate dehydrogenase increased 12/223 (5.4%) 8/222 (3.6%)
Gamma-glutamyltransferase increased 10/223 (4.5%) 12/222 (5.4%)
Metabolism and nutrition disorders
Hypokalaemia 57/223 (25.6%) 58/222 (26.1%)
Hypomagnesaemia 46/223 (20.6%) 51/222 (23%)
Hypocalcaemia 37/223 (16.6%) 30/222 (13.5%)
Hyponatraemia 25/223 (11.2%) 22/222 (9.9%)
Hyperglycaemia 16/223 (7.2%) 14/222 (6.3%)
Hypophosphataemia 16/223 (7.2%) 12/222 (5.4%)
Decreased appetite 54/223 (24.2%) 56/222 (25.2%)
Musculoskeletal and connective tissue disorders
Back pain 30/223 (13.5%) 34/222 (15.3%)
Bone pain 14/223 (6.3%) 12/222 (5.4%)
Nervous system disorders
Headache 45/223 (20.2%) 46/222 (20.7%)
Dizziness 31/223 (13.9%) 23/222 (10.4%)
Dysgeusia 19/223 (8.5%) 16/222 (7.2%)
Lethargy 12/223 (5.4%) 5/222 (2.3%)
Psychiatric disorders
Insomnia 24/223 (10.8%) 28/222 (12.6%)
Renal and urinary disorders
Renal failure acute 13/223 (5.8%) 8/222 (3.6%)
Renal impairment 12/223 (5.4%) 6/222 (2.7%)
Respiratory, thoracic and mediastinal disorders
Cough 39/223 (17.5%) 23/222 (10.4%)
Dyspnoea 18/223 (8.1%) 27/222 (12.2%)
Epistaxis 24/223 (10.8%) 17/222 (7.7%)
Hiccups 20/223 (9%) 20/222 (9%)
Oropharyngeal pain 13/223 (5.8%) 12/222 (5.4%)
Skin and subcutaneous tissue disorders
Rash 19/223 (8.5%) 48/222 (21.6%)
Pruritus 10/223 (4.5%) 16/222 (7.2%)
Urticaria 4/223 (1.8%) 16/222 (7.2%)
Vascular disorders
Hypertension 14/223 (6.3%) 18/222 (8.1%)
Hypotension 11/223 (4.9%) 20/222 (9%)
Flushing 7/223 (3.1%) 12/222 (5.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01014208
Other Study ID Numbers:
  • 110928
First Posted:
Nov 16, 2009
Last Update Posted:
Aug 7, 2015
Last Verified:
Feb 1, 2015