Trial Outcomes & Findings for Study of Bendamustine and Ofatumumab in Elderly Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy (NCT NCT01626352)

Last Updated: 2017-11-22

Results Overview

Disease response assessments will be performed using the International Working Group (IMW)-revised response criteria for malignant lymphoma (Cheson 2007). Complete response requires a disappearance of all evidence of disease.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

18 months

Results posted on

2017-11-22

Participant Flow

Between October 2012 to July 2014, 22 subjects with newly diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) were screened for enrollment in the study at 12 investigational sites in the U.S.. Of those, 21 were treated.

Participant milestones

Participant milestones
Measure	Bendamustine/Ofatumumab All patients will receive ofatumumab and bendamustine as an intravenous (IV) infusion for 6 cycles (a cycle is defined as 21 days in length). Bendamustine: via IV infusion, 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 Ofatumumab: via IV infusion, 1000-mg Days 1 and 8 during Cycle 1 only, and on Day 1 of Cycles 2 through 6
Overall Study STARTED	22
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Bendamustine/Ofatumumab All patients will receive ofatumumab and bendamustine as an intravenous (IV) infusion for 6 cycles (a cycle is defined as 21 days in length). Bendamustine: via IV infusion, 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 Ofatumumab: via IV infusion, 1000-mg Days 1 and 8 during Cycle 1 only, and on Day 1 of Cycles 2 through 6
Overall Study Disease Progression	3
Overall Study Intercurrent Illness	2
Overall Study Death	2
Overall Study Withdrawal by Subject	1
Overall Study Non-Compliance	1
Overall Study Never Treated	1

Baseline Characteristics

Study of Bendamustine and Ofatumumab in Elderly Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bendamustine/Ofatumumab n=21 Participants All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Bendamustine: via IV infusion, 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 Ofatumumab: via IV infusion, 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	21 Participants n=5 Participants
Age, Continuous	83 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: 18 months

Population: All patients treated with study drugs and having a post baseline response assessment.

Outcome measures

Outcome measures
Measure	Bendamustine/Ofatumumab n=21 Participants All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Bendamustine: via IV infusion, 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 Ofatumumab: via IV infusion, 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6
Number of Patients With a Complete Response	7 Participants

SECONDARY outcome

Timeframe: After cycles 3 and 6 of each 21-day cycle and every 3 months thereafter until disease progression or relapse from complete response for up to 38 months

Population: All patients treated with study drugs and having a post baseline response assessment of a complete or partial response.

Defined as the time from date of first documented confirmed response to date of disease progression or relapse from complete response as defined by the International Working Group (IMW)-revised response criteria for malignant lymphoma (Cheson 2007). This criteria categorizes the response of a patient's tumor to treatment as Complete Response (CR): the disappearance of all disease evidence; Partial Response (PR): regression of measurable disease and no new sites; Stable Disease (SD): less than a PR but not progressive disease (PD); Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir. Patients who are alive and free from disease progression will be censored at the date of last tumor assessment. Patients who begin further anticancer therapy prior to disease progression will be censored at the date of last tumor assessment prior to the start date of the anticancer therapy.

Outcome measures

Outcome measures
Measure	Bendamustine/Ofatumumab n=19 Participants All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Bendamustine: via IV infusion, 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 Ofatumumab: via IV infusion, 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6
Duration of Response	5.6 months Interval 2.9 to 9.8

SECONDARY outcome

Timeframe: After cycles 3 and 6 of each 21-day cycle, and every 3 months thereafter until progression or relapse from complete response for up to 40 months

Population: All enrolled patients who have received study treatment.

Defined as the time from date of first treatment to the date of first documented disease progression or relapse from complete response as defined by the International Working Group (IMW)-revised response criteria for malignant lymphoma (Cheson 2007). This criteria categorizes the response of a patient's tumor to treatment as Complete Response (CR): the disappearance of all disease evidence; Partial Response (PR): regression of measurable disease and no new sites; Stable Disease (SD): less than a PR but not progressive disease (PD); Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir.

Outcome measures

Outcome measures
Measure	Bendamustine/Ofatumumab n=21 Participants All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Bendamustine: via IV infusion, 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 Ofatumumab: via IV infusion, 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6
Time to Progression (TTP)	10.5 months Interval 4.5 to Not reached at this time

SECONDARY outcome

Timeframe: every 3 cycles during treatment and every 3 months thereafter until progression or death from any cause, projected 18 months

Population: All enrolled patients who have received study treatment.

Defined as the time from Day 1 of study drug administration to date of death from any cause.

Outcome measures

Outcome measures
Measure	Bendamustine/Ofatumumab n=21 Participants All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Bendamustine: via IV infusion, 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 Ofatumumab: via IV infusion, 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6
Overall Survival (OS)	12.0 months Interval 5.9 to 30.8

SECONDARY outcome

Timeframe: after cycles 3 and 6 of each 21-day cycle, and every 3 months thereafter, projected 18 months

Population: All patients treated with study drugs and having a post baseline response assessment.

Overall response is the number of patients with observed complete or partial response (CR or PR) as assessed using the International Working Group (IMW) revised response criteria for malignant lymphoma (Cheson 2007). Complete response requires disappearance of all evidence of disease. Partial response requires regression of measurable disease and no new sites.

Outcome measures

Outcome measures
Measure	Bendamustine/Ofatumumab n=21 Participants All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Bendamustine: via IV infusion, 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 Ofatumumab: via IV infusion, 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6
Overall Response (OR)	19 Participants

SECONDARY outcome

Timeframe: after cycles 3 and 6 of each 21-day cycle, and up to 30 days after last dose, projected 24 weeks

Population: All enrolled patients who received the study treatment.

A treatment-related adverse event was any untoward medical occurrence in a participant which was considered to have a relationship with the study drug (suspected to be possibly or probably related to the study drug per the Investigator's assessment). Adverse events were evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

Outcome measures

Outcome measures
Measure	Bendamustine/Ofatumumab n=21 Participants All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Bendamustine: via IV infusion, 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 Ofatumumab: via IV infusion, 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6
Number of Patients With Treatment-Related Adverse Events (AEs) as a Measure of Safety	16 Participants

SECONDARY outcome

Timeframe: After cycles 3 and 6 of each 21-day cycle, and every 3 months thereafter until progression or relapse from complete response for up to 40 months

Population: All enrolled patients who have received study treatment.

Defined as the time from first treatment until objective tumor progression, relapse from complete response, or death from any cause. Tumor response is defined by the International Working Group (IMW)-revised response criteria for malignant lymphoma (Cheson 2007). This criteria categorizes the response of a patient's tumor to treatment as Complete Response (CR): the disappearance of all disease evidence; Partial Response (PR): regression of measurable disease and no new sites; Stable Disease (SD): less than a PR but not progressive disease (PD); Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir. Patients who are alive and free from disease progression will be censored at the date of last tumor assessment.

Outcome measures

Outcome measures
Measure	Bendamustine/Ofatumumab n=21 Participants All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Bendamustine: via IV infusion, 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 Ofatumumab: via IV infusion, 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6
Progression-free Survival	8.6 months Interval 4.6 to 10.6

Adverse Events

Bendamustine/Ofatumumab

Serious events: 9 serious events

Other events: 20 other events

Deaths: 14 deaths

Serious adverse events

Serious adverse events
Measure	Bendamustine/Ofatumumab n=21 participants at risk All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Patients will receive as an IV infusion of bendamustine Days 1 and 2 of Cycles 1-6, ofatumumab Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2-6 (see Figure 1). Bendamustine: Patients will receive as an IV infusion bendamustine 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 and ofatumumab 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6(a cycle is defined as 21 days in length). Ofatumumab: Patients will receive as an IV infusion bendamustine 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 and ofatumumab 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6(a cycle is defined as 21 days in length).
Vascular disorders Pulmonary Embolism	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Vascular disorders Deep Vein Thrombosis	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Infections and infestations Pneumonia	9.5% 2/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Gastrointestinal disorders Abdominal distension	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Infections and infestations Abdominal infection	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Renal and urinary disorders Acute kidney injury	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Infections and infestations Cystitis	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
General disorders Death	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Metabolism and nutrition disorders Dehydration	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Gastrointestinal disorders Diarrhoea	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
General disorders Disease progression	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Injury, poisoning and procedural complications Fall	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
General disorders Fatigue	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Gastrointestinal disorders Gastrointestinal necrosis	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Investigations Haemoglobin decreased	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Investigations Platelet count decreased	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Nervous system disorders Syncope	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Infections and infestations Urinary tract infection	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Investigations White blood cell count decreased	4.8% 1/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.

Other adverse events

Other adverse events
Measure	Bendamustine/Ofatumumab n=21 participants at risk All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Patients will receive as an IV infusion of bendamustine Days 1 and 2 of Cycles 1-6, ofatumumab Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2-6 (see Figure 1). Bendamustine: Patients will receive as an IV infusion bendamustine 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 and ofatumumab 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6(a cycle is defined as 21 days in length). Ofatumumab: Patients will receive as an IV infusion bendamustine 90 mg/m\^2 Days 1 and 2 of Cycles 1 through 6 and ofatumumab 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6(a cycle is defined as 21 days in length).
General disorders Fatigue	47.6% 10/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Gastrointestinal disorders Nausea	42.9% 9/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Cough	28.6% 6/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Gastrointestinal disorders Diarrhoea	23.8% 5/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Blood and lymphatic system disorders Anaemia	19.0% 4/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Gastrointestinal disorders Constipation	19.0% 4/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Metabolism and nutrition disorders Decreased Appetite	19.0% 4/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
General disorders Infusion Related Reaction	19.0% 4/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Investigations Weight Decreased	19.0% 4/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
General disorders Oedema Peripheral	14.3% 3/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Skin and subcutaneous tissue disorders Pruritus	14.3% 3/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Gastrointestinal disorders Vomiting	14.3% 3/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
General disorders Asthenia	9.5% 2/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Cardiac disorders Chest Pain	9.5% 2/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Nervous system disorders Headache	9.5% 2/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Metabolism and nutrition disorders Hypoglycaemia	9.5% 2/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Metabolism and nutrition disorders Hypokalaemia	9.5% 2/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Vascular disorders Hypotension	9.5% 2/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Psychiatric disorders Insomnia	9.5% 2/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Blood and lymphatic system disorders Neutropenia	9.5% 2/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Investigations Neutrophil Count Decreased	9.5% 2/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Investigations Platelet Count Decreased	9.5% 2/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.
Skin and subcutaneous tissue disorders Urticaria	9.5% 2/21 • Collected once per week during cycle 1 and then collected once per month until 30 days after last treatment. All patients who received at least one dose of protocol treatment are included in the safety analysis.

Additional Information

Charles H. Davis

Sarah Cannon Research Institute

Phone: 615-524-4341

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
Publication restrictions are in place

Restriction type: OTHER