Trial Outcomes & Findings for An Open-Label Phase 2 Study of Ofatumumab (Arzerra) in Combination With Oral GSK2110183 in the Treatment of Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL) (NCT NCT01532700)

Last Updated: 2019-09-24

Results Overview

IWCLL Response Criteria 2008-Hallek. Complete response (CR): requires peripheral blood lymphocytes \< 4 x 109/L, absence of significant lymphadenopathy (\>1.5cm), no organomegaly, normal CBC, bone marrow must be at least normocellular; Complete Remission with incomplete bone marrow recovery (CRi): fulfill all the criteria for CR but have persistent anemia, thrombocytopenia or neutropenia apparently unrelated to disease activity but related to drug toxicity; Partial Remission (PR): ≥ 50% decrease in the peripheral blood lymphocytes from baseline, \> 50% reduction in the sum products of up to 6 lymph nodes, \> 50% reduction in hepatomegaly and/or neutrophils \> 1.5 x109/L, platelets \> 100 x109/L, hemoglobin \> 110 g/L; Stable Disease: Not CR, PR or PD (equivalent to nonresponse); Progressive Disease: Lymphadenopathy, or appearance of any new lesion/organomegaly, \> 50% increase in the size of the liver and/or spleen, \> 50% increase in the absolute number of circulating lymphocytes

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

36 months

Results posted on

2019-09-24

Participant Flow

Study enrollment was stopped as of 13 Sep 2016. 28 patients were enrolled. Data analysis is complete and manuscript has been being submitted.

Participant milestones

Participant milestones
Measure	Ofatumumab With GSK2110183 Ofatumumab with GSK2110183: - GSK2110183 125mg OD continuously \- Ofatumumab 300mg IV first dose, 2000mg weekly x 7 doses, then 2000mg monthly x 4 doses
Overall Study STARTED	28
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Open-Label Phase 2 Study of Ofatumumab (Arzerra) in Combination With Oral GSK2110183 in the Treatment of Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ofatumumab With GSK2110183 n=28 Participants Ofatumumab with GSK2110183: - GSK2110183 125mg OD continuously \- Ofatumumab 300mg IV first dose, 2000mg weekly x 7 doses, then 2000mg monthly x 4 doses
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=5 Participants
Age, Categorical >=65 years	13 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 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	26 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 Canada	28 participants n=5 Participants

PRIMARY outcome

Timeframe: 36 months

Outcome measures

Outcome measures
Measure	Ofatumumab With GSK2110183 n=28 Participants Ofatumumab with GSK2110183: - GSK2110183 125mg OD continuously \- Ofatumumab 300mg IV first dose, 2000mg weekly x 7 doses, then 2000mg monthly x 4 doses
Overall Response Rate, as Per the IWCLL 2008 Response Criteria Complete response	1 Participants
Overall Response Rate, as Per the IWCLL 2008 Response Criteria Partial response	13 Participants
Overall Response Rate, as Per the IWCLL 2008 Response Criteria Stable disease	14 Participants

SECONDARY outcome

Timeframe: 36 months

Outcome measures

Outcome measures
Measure	Ofatumumab With GSK2110183 n=28 Participants Ofatumumab with GSK2110183: - GSK2110183 125mg OD continuously \- Ofatumumab 300mg IV first dose, 2000mg weekly x 7 doses, then 2000mg monthly x 4 doses
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Dyspnea (%)	36 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Lung Infections (%)	18 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Response rate (%)	50 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Stable Disease (%)	50 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Upper respiratory Infections (%)	71 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Cough (%)	64 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Diarrhea (%)	61 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Upper respiratory infections (%)	71 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Skin (%)	32 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Urinary tract infection (%)	18 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Neutropenia Grade 3-4(%)	39 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Thrombocytopenia Grade 3-4 (%)	32 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Anemia Grade 3-4 (%)	25 percentage of participants
Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) Infusion related reactions (%)	75 percentage of participants

SECONDARY outcome

Timeframe: 36 months

Progression Free Survival (PFS) is defined as the length of time between the date of first dose of study treatment (GSK2110183) and the earliest date of disease progression or death due to any cause. Overall survival is defined as the length of time between the date of first dose of study treatment (GSK2110183) and death due to any cause.

Outcome measures

Outcome measures
Measure	Ofatumumab With GSK2110183 n=28 Participants Ofatumumab with GSK2110183: - GSK2110183 125mg OD continuously \- Ofatumumab 300mg IV first dose, 2000mg weekly x 7 doses, then 2000mg monthly x 4 doses
Median Progression Free Survival, Overall Survival Median PFS time (months)	8.5 months Interval 7.7 to 13.2
Median Progression Free Survival, Overall Survival 1 year overall survival time (months)	88.3 months Interval 76.6 to 100.0
Median Progression Free Survival, Overall Survival 2 year overall survival time	68.1 months Interval 46.0 to 100.0

SECONDARY outcome

Timeframe: 36 months

Duration of Response (DOR) is defined, for the subset of patients with a CR or PR, as the time from first documented evidence of CR or PR until first documented disease progression or death due to any cause. Duration of response will be summarized descriptively using Kaplan-Meier medians and quartiles.

Outcome measures

Outcome measures
Measure	Ofatumumab With GSK2110183 n=28 Participants Ofatumumab with GSK2110183: - GSK2110183 125mg OD continuously \- Ofatumumab 300mg IV first dose, 2000mg weekly x 7 doses, then 2000mg monthly x 4 doses
Median Duration of Response	6.4 months Interval 3.2 to 11.7

Adverse Events

Ofatumumab With GSK2110183

Serious events: 14 serious events

Other events: 27 other events

Deaths: 27 deaths

Serious adverse events

Serious adverse events
Measure	Ofatumumab With GSK2110183 n=27 participants at risk Ofatumumab with GSK2110183: - GSK2110183 125mg OD continuously \- Ofatumumab 300mg IV first dose, 2000mg weekly x 7 doses, then 2000mg monthly x 4 doses
Blood and lymphatic system disorders febrile neutropenia	3.7% 1/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Cardiac disorders Atrial Fibrillation	3.7% 1/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Infections and infestations Bronchial infection	3.7% 1/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Infections and infestations Lung infection	14.8% 4/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Infections and infestations Skin infection	7.4% 2/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Infections and infestations Upper respiratory infection	7.4% 2/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Musculoskeletal and connective tissue disorders Back pain ?Progressive CLL	3.7% 1/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of pulmonary origin	3.7% 1/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive squamous cell carcinoma-malignant	3.7% 1/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Renal and urinary disorders Bilateral hydronephrosis	3.7% 1/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.7% 1/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress	3.7% 1/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Reproductive system and breast disorders Pneumonitis	7.4% 2/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.

Other adverse events

Other adverse events
Measure	Ofatumumab With GSK2110183 n=27 participants at risk Ofatumumab with GSK2110183: - GSK2110183 125mg OD continuously \- Ofatumumab 300mg IV first dose, 2000mg weekly x 7 doses, then 2000mg monthly x 4 doses
General disorders Infusion related reaction	74.1% 20/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
General disorders Fever	48.1% 13/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Nervous system disorders Paresthesias	25.9% 7/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
General disorders Fatigue	29.6% 8/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Nervous system disorders Dizziness	22.2% 6/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Skin and subcutaneous tissue disorders Rash	37.0% 10/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Musculoskeletal and connective tissue disorders Back pain	22.2% 6/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Nervous system disorders Headache	18.5% 5/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Psychiatric disorders Insomnia	18.5% 5/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
General disorders leg edema	14.8% 4/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Nervous system disorders Dysgeusia	14.8% 4/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Respiratory, thoracic and mediastinal disorders Sore throat	22.2% 6/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Respiratory, thoracic and mediastinal disorders Cough	74.1% 20/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Gastrointestinal disorders Dyspepsia	29.6% 8/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Gastrointestinal disorders Nausea	29.6% 8/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Gastrointestinal disorders Abdominal pain	22.2% 6/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Metabolism and nutrition disorders Hyperglycemia	14.8% 4/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Blood and lymphatic system disorders Anemia	44.4% 12/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Investigations Neutropenia	37.0% 10/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.
Investigations Thrombocytopenia	29.6% 8/27 • Twenty-eight patients were evaluable for toxicity and response from the time of their first dose of afuresertib. Adverse events were graded using NCI Common Toxicity Criteria v4.03 at each visit. Patients were assessed four weeks after study discontinuation. Thereafter, for patients off-study for progressive disease, follow-up documented ongoing/late toxicities and death. For patients off-study with CR, PR, or SD, follow-up was every three months until progression or death.

Additional Information

Dr. Christine Chen

University Health Network

Phone: 416-946-2827

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place