Ofatumumab Bendamustine Combination Compared With Bendamustine Monotherapy in Indolent B-cell NHL Unresponsive to Rituxtherapy

Lymphoma, Follicular Clinical Trial

— A+B  

Official title:

Randomized Open Label of Ofatumumab and Bendamustine Combination Compared With Bendamustine Monotherapy in Indolent B-cell Non-Hodgkin's Lymphoma Unresponsive to Rituximab or a Rituximab-Containing Regimen During or Within Six Months of Treatment

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01077518
• Other study ID #: 110918
• Secondary ID: 2008-004177-17CO
• Status: Terminated
• Phase: Phase 3
• Start date: August 26, 2010
• Est. completion date: December 26, 2018

Study information

• Verified date: March 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to evaluate the safety and efficacy of ofatumumab and bendamustine combination therapy in patients with indolent B-cell NHL that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

Description:

Ofatumumab is an anti-CD20 monoclonal antibody shown to have monotherapy activity in patients with follicular lymphoma that has relapsed following rituximab-containing therapy. Bendamustine was approved by FDA for the treatment of in patients with indolent B-cell Non-Hodgkin's Lymphoma (NHL) that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

Biologics have demonstrated enhanced efficacy when added to chemotherapeutic combinations in the frontline treatment for indolent NHL. The combination of ofatumumab and bendamustine may provide additional clinical benefit and efficacy to those who no longer respond to rituximab or rituximab-containing regimens.

The objective of this study is to determine the effect of ofatumumab and bendamustine combination therapy in patients with indolent B-cell NHL that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 346
• Est. completion date: December 26, 2018
• Est. primary completion date: January 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Indolent lymphoma including Grades 1-3a follicular, small lymphocytic, lymphoplasmacytic, and marginal zone lymphoma; Stages III-IV, or bulky disease, Stage II. Tumor verified CD20+ and CT imaging done at screening verifying disease

• Indolent B-cell NHL that remains stable or unresponsive during or within 6 months of treatment with rituximab or a rituximab-containing regimen

• Indolent lymphoma including grades 1-3a follicular, small lymphocytic, lymphoplasmacytic, and marginal zone lymphoma; stages III-IV, or bulky disease stage II (i.e. as any single mass > 5 cm in any direction)

• ECOG Performance Status of 0, 1, or 2

• Life expectancy of at least 6 months

• 18 years or older

• Signed, written informed consent

Exclusion Criteria:

• Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to aggressive lymphoma

• Previous allogeneic stem cell transplant

• Previous autologous stem cell transplant, fludarabine therapy, or radioimmunotherapy in the past 12 months

• Previous external beam radiation therapy to the pelvis. Previous external beam radiation therapy for bony disease to the cranium, mediastinum, and axilla, or to two or to more than 3 vertebral bodies

• High dose steroids greater to or equal to 60 mg prednisone/day (or equivalent) within 3 months of randomization. No more than 10 mg prednisone (or equivalent) daily at the time of randomization

• Prior bendamustine treatment within 1 year of randomization not resulting in a CR or PR for at least 6 months

• Treatment with anti-CD20 monoclonal antibody within 3 months of randomization

• Known CNS involvement of indolent lymphoma

• Other past or current malignancy. Subjects free of malignancy for at least 5 years or have history of definitively treated non-melanoma skin cancer, or successfully treated in situ carcinoma, are eligible

• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment

• Clinically significant cardiac disease

• History of significant cerebrovascular disease or event with significant symptoms

• Positive serology for Hepatitis B

• Current active liver or biliary disease (except Gibber's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease)

• Known HIV positive

• Abnormal/inadequate blood values, liver and kidney function

• Current participation in other clinical study

• Inability to comply with the protocol activities

• Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• Ofatumumab
Ofatumumab was a liquid concentrate solution for infusion presented in glass vials containing 50 mL of solution at a concentration of 20 mg/mL to provide 1000 mg per vial. The ofatumumab infusions were prepared in 1000 mL sterile, pyrogen-free 0.9% NaCl to yield a 1 mg/mL ofatumumab concentration infusion.
• Bendamustine infusion
Bendamustine 100 mg/vial, injection
• Ofatumumab and Bendamustine infusions (Arm A)
Up to 8 cycles of Bendamustine (90 mg/m2 Days 1 and 2, every 21 days) given in combination with 12 doses of ofatumumab (1000 mg). Ofatumumab will be given on day 1 of each cycle of bendamustine as long as patients in Arm A receive bendamustine. Once patients in Arm A complete bendamustine therapy, the remaining doses of ofatumumab will be given monthly until all 12 doses are completed.
• Bendamustine infusion (Arm B)
Bendamustine (120 mg/m2 Days 1 and 2, every 21 days, up to 8 cycles).

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Capital Federal	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Buenos Aires
Argentina	Novartis Investigative Site	Derqui, Pilar	Buenos Aires
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Innsbruck
Austria	Novartis Investigative Site	Leoben
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Salzburg
Austria	Novartis Investigative Site	Steyr
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Brussels
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Barrie	Ontario
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Saskatoon	Saskatchewan
Canada	Novartis Investigative Site	Toronto	Ontario
France	Novartis Investigative Site	Avignon cedex 9
France	Novartis Investigative Site	Clermont-Ferrand Cedex 1
France	Novartis Investigative Site	Grenoble cedex 9
France	Novartis Investigative Site	La Roche sur Yon Cedex 9
France	Novartis Investigative Site	Le Mans
France	Novartis Investigative Site	Marseille Cedex 9
France	Novartis Investigative Site	Nantes cedex 1
France	Novartis Investigative Site	Nantes Cedex 2
France	Novartis Investigative Site	Pessac cedex
France	Novartis Investigative Site	Saint Pierre cedex
France	Novartis Investigative Site	Saint-Denis cedex
France	Novartis Investigative Site	Tours cedex 9
Germany	Novartis Investigative Site	Aschaffenburg	Bayern
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Bottrop	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Bremen
Germany	Novartis Investigative Site	Essen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Frankfurt	Hessen
Germany	Novartis Investigative Site	Fuerth	Bayern
Germany	Novartis Investigative Site	Giessen	Hessen
Germany	Novartis Investigative Site	Goch	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Hanau	Hessen
Germany	Novartis Investigative Site	Herford	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Kaiserslautern	Rheinland-Pfalz
Germany	Novartis Investigative Site	Kassel	Hessen
Germany	Novartis Investigative Site	Koblenz	Rheinland-Pfalz
Germany	Novartis Investigative Site	Leverkusen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Mannheim	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Marburg	Hessen
Germany	Novartis Investigative Site	Muenchen	Bayern
Germany	Novartis Investigative Site	Muenchen	Bayern
Germany	Novartis Investigative Site	Neunkirchen	Saarland
Germany	Novartis Investigative Site	Paderborn	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Recklinghausen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Weilheim	Bayern
Greece	Novartis Investigative Site	Alexandroupolis
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens,
Greece	Novartis Investigative Site	Haidari, Athens
Greece	Novartis Investigative Site	Heraklion, Crete
Greece	Novartis Investigative Site	Ioannina
Greece	Novartis Investigative Site	Piraeus
Hong Kong	Novartis Investigative Site	Shatin, New Territories
Hong Kong	Novartis Investigative Site	Tuen Mun
Italy	Novartis Investigative Site	Genova	Liguria
Italy	Novartis Investigative Site	Meldola (FC)	Emilia-Romagna
Italy	Novartis Investigative Site	Milano	Lombardia
Italy	Novartis Investigative Site	Milano	Lombardia
Italy	Novartis Investigative Site	Napoli	Campania
Italy	Novartis Investigative Site	Novara	Piemonte
Italy	Novartis Investigative Site	Reggio Calabria	Calabria
Italy	Novartis Investigative Site	Roma	Lazio
Italy	Novartis Investigative Site	San Giovanni Rotondo	Puglia
Italy	Novartis Investigative Site	Terni	Umbria
Italy	Novartis Investigative Site	Verona	Veneto
Japan	Novartis Investigative Site	Aichi
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Hiroshima
Japan	Novartis Investigative Site	Hyogo
Japan	Novartis Investigative Site	Ibaraki
Japan	Novartis Investigative Site	Kanagawa
Japan	Novartis Investigative Site	Miyagi
Japan	Novartis Investigative Site	Okayama
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Tokyo
Japan	Novartis Investigative Site	Tokyo
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Gdynia
Poland	Novartis Investigative Site	Legnica
Poland	Novartis Investigative Site	Opole
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Poland	Novartis Investigative Site	Wroclaw
Puerto Rico	Novartis Investigative Site	Hato Rey
Puerto Rico	Novartis Investigative Site	San Juan
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Kaluga
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Nizhniy Novgorod
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	Penza
Russian Federation	Novartis Investigative Site	St'Petersburg
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	Tula
Russian Federation	Novartis Investigative Site	Ufa,
Russian Federation	Novartis Investigative Site	Volgograd
Slovakia	Novartis Investigative Site	Bratislava
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Lviv
Ukraine	Novartis Investigative Site	Makiivka
United Kingdom	Novartis Investigative Site	Harrow
United Kingdom	Novartis Investigative Site	Northwood	Middlesex
United Kingdom	Novartis Investigative Site	Plymouth	Devon
United Kingdom	Novartis Investigative Site	Southampton
United Kingdom	Novartis Investigative Site	Uxbridge
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Beverly Hills	California
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Coeur d'Alene	Idaho
United States	Novartis Investigative Site	Danville	Pennsylvania
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Mineola	New York
United States	Novartis Investigative Site	Morgantown	West Virginia
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	Palm Springs	California
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Silver Spring	Maryland
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigative Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Canada,  France,  Germany,  Greece,  Hong Kong,  Italy,  Japan,  Poland,  Puerto Rico,  Russian Federation,  Slovakia,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) as Assessed by the Independent Review Committee (IRC)	PFS is defined as the time interval between randomization until disease progression or death (due to any cause).	From randomization to the date of first documented disease progression or death due to any cause (67.5 months)
Secondary	Progression-free Survival (PFS) in Participants With Follicular Lymphoma (FL) Per IRC	PFS is defined as the time interval between randomization until disease progression or death (due to any cause).	From randomization to the date of first documented disease progression or death due to any cause (67.5 months)
Secondary	Overall Response Rate (ORR) in All Participants Per IRC	ORR: Percentage of subjects achieving complete response (CR) or partial response (PR) from the start of randomization until disease progression or the start of new anti-cancer therapy, including the optional ofatumumab for subjects in Arm B based on responses from the IRC assessment of best overall response using the Revised Response Criteria for Malignant Lymphoma (RRCML). Response criteria is CR, PR, standard disease (SD), progressive disease (PD) or not estimable. CR is the complete disappearance of all detectable clinical evidence of disease & disease-related symptoms. PR is at least a 50% decrease from baseline in the sum of the product of the diameters (SPD) of target lesions. SD is failure to attain the criteria needed for a CR, PR or PD. PD is the appearance of any new lesion more than 1.5 cm in any axis or at least a 50% increase from nadir in the SPD of target or non target lesions or at least a 50% increase in the longest diameter(SLD) or any Target or non target lesions.	From randomization until the 217th PFS event occurred, up to about 67.5 months
Secondary	Overall Response Rate (ORR) in Participants With FL Per IRC	ORR: Percentage of subjects achieving complete response (CR) or partial response (PR) from the start of randomization until disease progression or the start of new anti-cancer therapy, including the optional ofatumumab for subjects in Arm B based on responses from the IRC assessment of best overall response using the Revised Response Criteria for Malignant Lymphoma (RRCML). Response criteria is CR, PR, standard disease (SD), progressive disease (PD) or not estimable. CR is the complete disappearance of all detectable clinical evidence of disease & disease-related symptoms. PR is at least a 50% decrease from baseline in the sum of the product of the diameters (SPD) of target lesions. SD is failure to attain the criteria needed for a CR, PR or PD. PD is the appearance of any new lesion more than 1.5 cm in any axis or at least a 50% increase from nadir in the SPD of target or non target lesions or at least a 50% increase in the longest diameter(SLD) or any Target or non target lesions.	From randomization until the 217th PFS event occurred, up to about 67.5 months
Secondary	Overall Survival (OS) in All Participants	The interval of time between the date of randomization and the date of death due to any cause. For subjects who are alive, time of death will be censored at the date of last contact.	From randomization up to about 89 months
Secondary	Overall Survival (OS) in Participants With FL	The interval of time between the date of randomization and the date of death due to any cause. For subjects who are alive, time of death will be censored at the date of last contact.	From randomization up to about 89 months
Secondary	Time to Response in All Participants Per IRC	Time to response = time from randomization to the first response (CR/ PR). If no CR/PR value was present data was to be censored at last adequate assessment.	From randomization to up to 67.5 months
Secondary	Time to Response in Participants With FL Per IRC	Time to response = time from randomization to the first response (CR/ PR). If no CR/PR value was present data was to be censored at last adequate assessment.	From randomization to up to 67.5 months
Secondary	Duration of Response in All Participants Per IRC	Time (in months) from the initial response (CR/PR) to first documented sign of disease progression or death due to any cause.	time from the initial response (CR/PR) (Day 84) to first documented sign of disease progression or death due to any cause up to 67.5 months
Secondary	Duration of Response in Participants With FL Per IRC	Time (in months) from the initial response (CR/PR) to first documented sign of disease progression or death due to any cause.	time from the initial response (CR/PR) (Day 84) to first documented sign of disease progression or death due to any cause up to 67.5 months
Secondary	Time to Progression in All Participants Per IRC	Time from randomization until disease progression	From randomization to the date of first documented disease progression, whichever occurred first, reported betwen day of first participant randomized up to about 67.5 months
Secondary	Time to Progression in Participants With FL Per IRC	Time from randomization until disease progression	From randomization to the date of first documented disease progression, whichever occurred first, reported betwen day of first participant randomized up to about 67.5 months
Secondary	Time to Next Therapy in All Participants Per IRC	Time to next therapy was defined as the time (in months) from randomization date to the date of receiving the next line treatment, including all therapy types.	from randomization date to the date of receiving the next line treatment or death, up to 67.5 months
Secondary	Time to Next Therapy in Participants With FL Per IRC	Time to next therapy was defined as the time (in months) from randomization date to the date of receiving the next line treatment, including all therapy types	from randomization date to the date of receiving the next line treatment or death, up to 67.5 months
Secondary	PRO - Change From Baseline in Health Related Quality of Life (HRQL) Measures in All Participants: The FACT-Lym	The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) is intended as a lymphoma specific additional concerns subscale that is designed to supplement the FACT-G. The subscale consists of 15 items. Subjects respond to the items on a five point Likert scale ranging from 0 'Not at all' to 4 'Very much'. Subscale scores are calculated by summing individual items to obtain a score, then multiplying the sum of the item scores by the number of items in the subscale, then dividing by the number of items answered. The Score range is 0 -28 for Physical Well-Being, Social/Family Well-Being, 0 -24 for Functional Well-Being and 0 - 60 for the Lymphoma subscale (LYMS). FACT lymphoma TOI is the sum of Physical, Functional Well-Being & Lymphoma scores. FACT-G Total Score is the sum of Physical, Emotional, Social and Functional Well-Being scores. FACT-Lymph is the sum of Physical, Social, Emotional, Functional and Lymphoma scores. The higher the score, the better the QOL. C =cycle; D=Day	administered at the screening visit and C5D1 (month 5), C11D1 (month 11), D252, 12m post-D252, withdrawal (24m post-D252) up to 67.5 months; Cycle = 21 days
Secondary	PRO - Change From Baseline in Health Related Quality of Life (HRQL) Measures in Participants With FL: The FACT-Lym	The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) is intended as a lymphoma specific additional concerns subscale that is designed to supplement the FACT-G. The subscale consists of 15 items. Subjects respond to the items on a five point Likert scale ranging from 0 'Not at all' to 4 'Very much'. Subscale scores are calculated by summing individual items to obtain a score, then multiplying the sum of the item scores by the number of items in the subscale, then dividing by the number of items answered. The Score range is 0 -28 for Physical Well-Being, Social/Family Well-Being, 0 -24 for Functional Well-Being and 0 - 60 for the Lymphoma subscale (LYMS). FACT lymphoma TOI is the sum of Physical, Functional Well-Being & Lymphoma scores. FACT-G Total Score is the sum of Physical, Emotional, Social and Functional Well-Being scores. FACT-Lymph is the sum of Physical, Social, Emotional, Functional and Lymphoma scores. The higher the score, the better the QOL. C =cycle; D=Day	administered at the screeing visit and C5D1 (month 5), C11D1 (month 11), D252, 12m post-D252, withdrawal (24m post-D252) up to 67.5 months; Cycle = 21 days
Secondary	PRO - Change From Baseline in HRQL Measures in All Participants: The EQ-5D	The EuroQoL Five-Dimension (EQ-5D) is a self-administered, generic, indirect utility measure used for health economic analysis.EQ-5D should be answered as one of 3 levels about current condition for 5 dimensions and was calculated total average by giving a weighting on 3 level of answers (EQ-5D levels into 'no problems' (level 1) and 'problems' (level 2 and 3)).; Table of scores by each level for EQ-5D items: mobility(level 1=0, level2=0.069,level 3=0.314), self care(level 1=0, level2=0.104,level 3=0.214), usual activities(level 1=0, level2=0.036,level 3=0.094), pain/discomfort (level 1=0, level2=0.,level 3=0.386) and anxiety/depression(level 1=0, level2=0.071,level 3=0.2); *EQ-5D Total = 1 - 0.081 - (the score of the each level) - 0.269 (if at least one of level 3 presents)	administered at screening and C5D1 (month 5), C11D1 (month 11), D252, 12m post-D252, withdrawal (24m post-D252) up to 67.5 months; Cycle = 21 days
Secondary	PRO - Change From Baseline in HRQL Measures in Participants With FL: The EQ-5D	The EuroQoL Five-Dimension (EQ-5D) is a self-administered, generic, indirect utility measure used for health economic analysis.EQ-5D should be answered as one of 3 levels about current condition for 5 dimensions and was calculated total average by giving a weighting on 3 level of answers (EQ-5D levels into 'no problems' (level 1) and 'problems' (level 2 and 3)).; Table of scores by each level for EQ-5D items: mobility(level 1=0, level2=0.069,level 3=0.314), self care(level 1=0, level2=0.104,level 3=0.214), usual activities(level 1=0, level2=0.036,level 3=0.094), pain/discomfort (level 1=0, level2=0.,level 3=0.386) and anxiety/depression(level 1=0, level2=0.071,level 3=0.2); *EQ-5D Total = 1 - 0.081 - (the score of the each level) - 0.269 (if at least one of level 3 presents)	administered at screening and C5D1 (month 5), C11D1 (month 11), D252, 12m post-D252, withdrawal (24m post-D252) up to 67.5 months; Cycle = 21 days
Secondary	PRO - Change in Health Treatment in HRQL Measures in All Participants: The Health Change Questionnaire (HCQ)	The Health Change Questionnaire,(HCQ) used is a nine item scale that asks the patient to rate change in status since beginning treatment on this study. For HCQ, values from 1 to 9 were assigned to the 9 responses in the HCQ questionnaire, ranging from 1 for 'my health is a great deal better' to 9 for 'my health is a great deal worse' since the beginning of the study. Lower scores represent better conditions	administered at screening and C5D1 (month 5), C11D1 (month 11), D252, 12m post-D252, withdrawal (24m post-D252) up to 67.5 months; Cycle = 21 days
Secondary	PRO - Change in Health Treatment in HRQL Measures in Participants With FL: The Health Change Questionnaire (HCQ)	The Health Change Questionnaire, (HCQ) used is a nine item scale that asks the patient to rate change in status since beginning treatment on this study. For HCQ, values from 1 to 9 were assigned to the 9 responses in the HCQ questionnaire, ranging from 1 for 'my health is a great deal better' to 9 for 'my health is a great deal worse' since the beginning of the study. Lower scores represent better conditions	administered at screening and C5D1 (month 5), C11D1 (month 11), D252, 12m post-D252, withdrawal (24m post-D252) up to 67.5 months; Cycle = 21 days
Secondary	Reduction in Tumor Size	Tumor size was measured by the mean change in the sum of the products of the greatest diameter (SPD) of the largest abnormal nodes from baseline to post-baseline by CT Scan.	baseline, post-baseline (up to 55 months)
Secondary	Summary of Change in Eastern Cooperative Oncology Group (ECOG) Performance Status	This is the number of participants with change in ECOG status. Change is measured categorically by "Improvement, deterioration and No change". Improvement is defined as decrease from baseline by at least one step on the ECOG performance status scale. Deteriorations is defined as increase from baseline by at least one step on the ECOG performance status scale. ECOG status to evaluate daily living: 0: Fully active, able to carry on all pre-disease performance without restriction; 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4: Completely disabled; cannot carry on any self care.Totally confined to bed or chai; 5: Dead	administered at screening and C5D1 (month 5), C11D1 (month 11), D252, 12m post-D252, withdrawal (24m post-D252) up to 67.5 months; Cycle = 21 days
Secondary	Summary of Number of Participants With Human Anti-Human Antibodies (HAHA)	A summary by responders and non-responders	From randomization up to about 67.5 months
Secondary	Overall Response Rate (ORR) to Optional Ofatumumab Monotherapy in Subjects Who Progressed During or Following Single-agent Bendamustine	ORR: Percentage of subjects achieving complete response (CR) or partial response (PR) from the start of randomization until disease progression or the start of new anti-cancer therapy, including the optional ofatumumab for subjects in Arm B based on responses from the IRC assessment of best overall response using the Revised Response Criteria for Malignant Lymphoma (RRCML). Response criteria is CR, PR, standard disease (SD), progressive disease (PD) or not estimable. CR is the complete disappearance of all detectable clinical evidence of disease & disease-related symptoms. PR is at least a 50% decrease from baseline in the sum of the product of the diameters (SPD) of target lesions. SD is failure to attain the criteria needed for a CR, PR or PD. PD is the appearance of any new lesion more than 1.5 cm in any axis or at least a 50% increase from nadir in the SPD of target or non target lesions or at least a 50% increase in the longest diameter(SLD) or any Target or non target lesions.	From randomization until the 217th PFS event occurred, up to about 67.8 months
Secondary	Quantitative Assessments of Immunoglobulins A, G and M (IgA, IgG, IgM)	at scheduled visits for actual values as well as for change from baseline	Screening, C1D1, 1M post D252, 6M post D252, 12M post D252 up to 67.5 months; Cycle = 21 days
Secondary	Plasma Ofatumumab Concentrations	Concentrations of ofatumumab in plasma listed by actual relative time and summarized by nominal time.	C1D1, C7D1, C12D1, C1D1, C12D1, 12M post-D252, withdrawal up to 12 months follow up
Secondary	B-cell Monitoring (CD19+, CD20+)	The percent change of CD5+CD19+ and CD5-CD19+ from baseline was summarized to assess the treatment effect, to monitor the normal B-cell population, and to follow their recovery.	C5D1 (month 5), 1M post-D252, 9M post-D252, up to 67.5 months; Cycle = 21 days
Secondary	Human Anti-chimeric Antibodies (HACA) Over Time	The number of participants with positive and negative baseline HACA results	At Baseline and Cycle 1 day 1