Ofatumumab for Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

• Sponsor: SCRI Development Innovations, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT01113632
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 77
• Locations: 13
• Arms: 2
• Duration (Months): 73
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The risk of immunosuppression deters many patients from receiving fludarabine, while combination chemotherapy regimens are poorly tolerated by elderly or infirm chronic lymphocytic leukemia (CLL) patients. Previous studies by our group and others have shown that rituximab is safe and well tolerated when used as a single agent in patients with CLL. In addition, maintenance therapy with rituximab was well tolerated by CLL patients, with probable prolongation of progression-free survival (Hainsworth et al. 2003). Based on pre clinical and clinical studies indicating possible increased efficacy of ofatumumab in patients with CLL, we wish to develop an antibody-only regimen for older patients and patients who refuse fludarabine-based regimens.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma	Drug: Ofatumumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Ofatumumab for Older Patients and Patients Who Refuse Fludarabine-Based Regimens With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ofatumumab 1000mg Ofatumumab 300mg IV Day 1 followed by ofatumumab 1000mg weekly for a total of 8 weeks	Drug: Ofatumumab; IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.
Experimental: Ofatumumab 2000mg Ofatumumab 300mg IV Day 1 followed by ofatumumab 2000mg weekly for a total of 8 weeks	Drug: Ofatumumab; IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [18 months]

   The Number of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. Progression-free Survival (PFS) [18 months]

   To assess the overall response rate of patients with previously untreated CLL or SLL receiving ofatumumab.

2. Number of Complete Responses [18 Months]

   The Number of Patients Who Experience a Complete Response From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions

3. Number of Partial Responses [18 Months]

   The Number of Patients Who Experience a Partial Response From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions

4. Safety of the Treatment Regimen [18 Months]

   Listing of all non-serious Adverse Events ocurring in 5% of patients or more

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. CD20+ B-cell chronic lymphocytic leukemia (B-CLL) or small lymphocytic lymphoma according to NCI criteria (see Appendix B).

2. Previously untreated CLL or small lymphocytic lymphoma (SLL).

3. Patients must require treatment according to NCI-Working Group guidelines (see Appendix C).

4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2 (see Appendix A).

5. Laboratory values as follows ≤7 days of initiation of treatment:

• Creatinine <3.0 mg/dL

• Aspartate amino transferase (AST) or alanine amino transferase (ALT) and alkaline phosphatase (ALP) must be <3 x upper limit of normal (ULN)

• Total bilirubin <1.5 x the institutional ULN

1. Patients must be hepatitis B sAg negative. Note: Patients who are HepB sAg negative but are HepB cAb positive (regardless of HepB sAb status) will NOT be allowed.

2. Women of childbearing potential must have a negative serum pregnancy test performed ≤7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.

3. Patients ≤ 65 years of age, or patients 18-64 years of age who have declined fludarabine-based regimens, are eligible.

4. Patient must be accessible for treatment and follow-up.

5. Patients must be able to understand the nature of this study, give written informed consent prior to study entry, and comply with study requirements.

Exclusion Criteria:

1. Previous therapy for CLL/SLL. (Patients who have received steroids or IVIG for autoimmune complications of CLL are eligible).

2. Current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease, per assessment by the treating physician).

3. Active bacterial or viral infection, or infection requiring intravenous antibiotic treatment at the time of accrual.

4. Central nervous system lymphoma/CLL.

5. Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (i.e., Richters transformation).

6. History of other malignancy within 2 years of study entry which could affect compliance with the protocol or interpretation of results. Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, low grade, early-stage, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ (DCIS) of the breast treated with curative intent, are generally eligible. These cases should be discussed with the study chair or study co-chair prior to enrollment.

7. Patients who are HepB sAg positive and/or HepB cAb positive.

8. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.

9. Any condition that would prevent patient comprehension of the nature of, and risk associated with, the study.

10. A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.

11. A major surgical procedure, open biopsy, or significant traumatic injury ≤28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study.

12. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to visit 1, whichever is longer. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Los Robles	Thousand Oaks	California	United States	91360
2	Florida Cancer Specialists	Ft. Myers	Florida	United States	34236
3	Woodlands Medical Specialists	Pensacola	Florida	United States	32503
4	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
5	Providence Medical Group	Terre Haute	Indiana	United States	47802
6	St. Louis Cancer Care	Chesterfield	Missouri	United States	63017
7	Portsmouth Regional Hospital	Portsmouth	New Hampshire	United States	03801
8	Hematology-Oncology Associates of Northern NJ	Morristown	New Jersey	United States	07960
9	Oncology Hematology Care	Cincinnati	Ohio	United States	45242
10	The Ohio State University	Columbus	Ohio	United States	43210
11	South Carolina Oncology Associates	Columbia	South Carolina	United States	29210
12	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee	United States	37404
13	Tennessee Oncology	Nashville	Tennessee	United States	37203

Sponsors and Collaborators

• SCRI Development Innovations, LLC
• GlaxoSmithKline

Investigators

• Study Chair: Ian Flinn, M.D., SCRI Development Innovations, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT01113632
• Other Study ID Numbers: SCRI CLL 11
• First Posted: Apr 30, 2010
• Last Update Posted: Sep 20, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by SCRI Development Innovations, LLC: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Ofatumumab
• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Ofatumumab

Study Results

Participant Flow

Arm/Group Title	Ofatumumab 1000mg	Ofatumumab 2000mg
Arm/Group Description	Ofatumumab 300mg IV Day 1 followed by ofatumumab 1000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.	Ofatumumab 300mg IV Day 1 followed by ofatumumab 2000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.
Period Title: Overall Study
STARTED	33	44
COMPLETED	2	19
NOT COMPLETED	31	25

Baseline Characteristics

Arm/Group Title	Ofatumumab 1000mg	Ofatumumab 2000mg	Total
Arm/Group Description	Ofatumumab 300mg IV Day 1 followed by ofatumumab 1000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.	Ofatumumab 300mg IV Day 1 followed by ofatumumab 2000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.	Total of all reporting groups
Overall Participants	33	44	77
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	75	69	72
Sex: Female, Male (Count of Participants)
Female	17 51.5%	19 43.2%	36 46.8%
Male	16 48.5%	25 56.8%	41 53.2%
Region of Enrollment (participants) [Number]
United States	33 100%	44 100%	77 100%

Outcome Measures

1. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	To assess the overall response rate of patients with previously untreated CLL or SLL receiving ofatumumab.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab 1000mg	Ofatumumab 2000mg
Arm/Group Description	Ofatumumab 300mg IV Day 1 followed by ofatumumab 1000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 1000 mg.	Ofatumumab 300mg IV Day 1 followed by ofatumumab 2000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.
Measure Participants	33	44
Median (95% Confidence Interval) [months]	19.8	32.5

2. Primary Outcome

Title	Overall Response Rate (ORR)
Description	The Number of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All patients who were evaluable for a response assessment

Arm/Group Title	Ofatumumab 1000mg	Ofatumumab 2000mg
Arm/Group Description	Ofatumumab 300mg IV Day 1 followed by ofatumumab 1000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 1000 mg.	Ofatumumab 300mg IV Day 1 followed by ofatumumab 2000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.
Measure Participants	28	44
Number [participants]	15 45.5%	30 68.2%

3. Secondary Outcome

Title	Number of Complete Responses
Description	The Number of Patients Who Experience a Complete Response From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions
Time Frame	18 Months

Outcome Measure Data

Analysis Population Description

All patients who were evaluable for a response assessment

Arm/Group Title	Ofatumumab 1000mg	Ofatumumab 2000mg
Arm/Group Description	Ofatumumab 300mg IV Day 1 followed by ofatumumab 1000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 1000 mg.	Ofatumumab 300mg IV Day 1 followed by ofatumumab 2000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.
Measure Participants	28	44
Number [participants]	2 6.1%	0 0%

4. Secondary Outcome

Title	Number of Partial Responses
Description	The Number of Patients Who Experience a Partial Response From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions
Time Frame	18 Months

Outcome Measure Data

Analysis Population Description

All patients who were evaluable for a response assessment

Arm/Group Title	Ofatumumab 1000mg	Ofatumumab 2000mg
Arm/Group Description	Ofatumumab 300mg IV Day 1 followed by ofatumumab 1000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 1000 mg.	Ofatumumab 300mg IV Day 1 followed by ofatumumab 2000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.
Measure Participants	28	44
Number [participants]	13 39.4%	30 68.2%

5. Secondary Outcome

Title	Safety of the Treatment Regimen
Description	Listing of all non-serious Adverse Events ocurring in 5% of patients or more
Time Frame	18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab 1000mg	Ofatumumab 2000mg
Arm/Group Description	Ofatumumab 300mg IV Day 1 followed by ofatumumab 1000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 1000 mg.	Ofatumumab 300mg IV Day 1 followed by ofatumumab 2000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.
Measure Participants	33	44
Fatigue	12 36.4%	21 47.7%
Allergic reaction	14 42.4%	16 36.4%
Anemia	14 42.4%	13 29.5%
Pain	9 27.3%	14 31.8%
Platelet count decreased	13 39.4%	10 22.7%
Rash	7 21.2%	16 36.4%
White blood cell decreased	10 30.3%	9 20.5%
Cough	5 15.2%	13 29.5%
Diarrhea	8 24.2%	9 20.5%
Neutrophil count decreased	7 21.2%	10 22.7%
Dyspnea	6 18.2%	9 20.5%
Hyperglycemia	4 12.1%	11 25%
Edema	8 24.2%	6 13.6%
Nausea	3 9.1%	11 25%
Infections and infestations - Other, unspecified	6 18.2%	7 15.9%
Peripheral sensory neuropathy	2 6.1%	11 25%
Constipation	2 6.1%	10 22.7%
Insomnia	3 9.1%	9 20.5%
Psychiatric disorders - Other, unspecified	5 15.2%	7 15.9%
Arthralgia	4 12.1%	7 15.9%
Dizziness	5 15.2%	5 11.4%
Hyperhidrosis	6 18.2%	4 9.1%
Hypocalcemia	4 12.1%	5 11.4%
Aspartate aminotransferase increased	6 18.2%	2 4.5%
Blood bilirubin increased	2 6.1%	6 13.6%
Oral pain	1 3%	7 15.9%
Respiratory, thoracic and mediastinal disorders	3 9.1%	5 11.4%
Non-cardiac chest pain	1 3%	6 13.6%
Pruritus	4 12.1%	3 6.8%
Abdominal pain	2 6.1%	4 9.1%
Allergic rhinitis	3 9.1%	3 6.8%
Anorexia	2 6.1%	4 9.1%
Back pain	2 6.1%	4 9.1%
Fever	2 6.1%	4 9.1%
Gastrointestinal disorders - Other, unknown	3 9.1%	3 6.8%
Headache	4 12.1%	2 4.5%
Hypertension	3 9.1%	3 6.8%
Hyponatremia	4 12.1%	2 4.5%
Dysgeusia	2 6.1%	3 6.8%
Flushing	1 3%	4 9.1%
Gastroesophageal reflux disease	3 9.1%	2 4.5%
Hypoglycemia	2 6.1%	3 6.8%
Musculoskeletal and connective tissue disorders	2 6.1%	3 6.8%
Skin and subcutaneous tissue disorders - Other	4 12.1%	1 2.3%
Upper respiratory infection	0 0%	5 11.4%
Vomiting	1 3%	4 9.1%
Alanine aminotransferase increased	2 6.1%	2 4.5%
Blurred vision	4 12.1%	0 0%
Bruising	1 3%	3 6.8%
Chills	1 3%	3 6.8%
Creatinine increased	1 3%	3 6.8%
Hypokalemia	1 3%	3 6.8%
Infusion related reaction	1 3%	3 6.8%
Urinary frequency	1 3%	3 6.8%
Weight loss	2 6.1%	2 4.5%

Adverse Events

Time Frame	18 Months
Arm/Group Title	Ofatumumab 1000mg		Ofatumumab 2000mg
Arm/Group Description	Ofatumumab 300mg IV Day 1 followed by ofatumumab 1000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.		Ofatumumab 300mg IV Day 1 followed by ofatumumab 2000mg weekly for a total of 8 weeks Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.
All Cause Mortality
	Ofatumumab 1000mg		Ofatumumab 2000mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ofatumumab 1000mg		Ofatumumab 2000mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/33 (9.1%)		2/44 (4.5%)
Blood and lymphatic system disorders
Anemia	1/33 (3%)		0/44 (0%)
Gastrointestinal disorders
Gastrointestinal disorders - Other, hernia	1/33 (3%)		0/44 (0%)
Gastrointestinal disorders - Other, unknown	1/33 (3%)		0/44 (0%)
Vomiting	1/33 (3%)		0/44 (0%)
General disorders
Edema	1/33 (3%)		0/44 (0%)
Fever	1/33 (3%)		0/44 (0%)
Investigations
Cholesterol high	1/33 (3%)		0/44 (0%)
Creatinine increased	0/33 (0%)		1/44 (2.3%)
Metabolism and nutrition disorders
Hypoalbuminemia	1/33 (3%)		0/44 (0%)
Nervous system disorders
Dysgeusia	1/33 (3%)		0/44 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/33 (3%)		0/44 (0%)
Pneumonitis	0/33 (0%)		1/44 (2.3%)
Skin and subcutaneous tissue disorders
Urticaria	1/33 (3%)		0/44 (0%)
Other (Not Including Serious) Adverse Events
	Ofatumumab 1000mg		Ofatumumab 2000mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/33 (97%)		42/44 (95.5%)
Blood and lymphatic system disorders
Anemia	14/33 (42.4%)		13/44 (29.5%)
Eye disorders
Blurred vision	4/33 (12.1%)		0/44 (0%)
Gastrointestinal disorders
Diarrhea	8/33 (24.2%)		9/44 (20.5%)
Nausea	3/33 (9.1%)		11/44 (25%)
Constipation	2/33 (6.1%)		10/44 (22.7%)
Oral pain	1/33 (3%)		7/44 (15.9%)
Abdominal pain	2/33 (6.1%)		4/44 (9.1%)
Gastrointestinal disorders - Other, unknown	3/33 (9.1%)		3/44 (6.8%)
Gastroesophageal reflux disease	3/33 (9.1%)		2/44 (4.5%)
Vomiting	1/33 (3%)		4/44 (9.1%)
General disorders
Fatigue	12/33 (36.4%)		21/44 (47.7%)
Pain	9/33 (27.3%)		14/44 (31.8%)
Edema	8/33 (24.2%)		6/44 (13.6%)
Non-cardiac chest pain	1/33 (3%)		6/44 (13.6%)
Fever	2/33 (6.1%)		4/44 (9.1%)
Chills	1/33 (3%)		3/44 (6.8%)
Infusion related reaction	1/33 (3%)		3/44 (6.8%)
Immune system disorders
Allergic reaction	14/33 (42.4%)		16/44 (36.4%)
Infections and infestations
Infections and infestations - Other, unspecified	6/33 (18.2%)		7/44 (15.9%)
Upper respiratory infection	0/33 (0%)		5/44 (11.4%)
Injury, poisoning and procedural complications
Bruising	1/33 (3%)		3/44 (6.8%)
Investigations
Platelet count decreased	13/33 (39.4%)		10/44 (22.7%)
White blood cell decreased	10/33 (30.3%)		9/44 (20.5%)
Neutrophil count decreased	7/33 (21.2%)		10/44 (22.7%)
Aspartate aminotransferase increased	6/33 (18.2%)		2/44 (4.5%)
Blood bilirubin increased	2/33 (6.1%)		6/44 (13.6%)
Alanine aminotransferase increased	2/33 (6.1%)		2/44 (4.5%)
Creatinine increased	1/33 (3%)		3/44 (6.8%)
Weight loss	2/33 (6.1%)		2/44 (4.5%)
Metabolism and nutrition disorders
Hyperglycemia	4/33 (12.1%)		11/44 (25%)
Hypocalcemia	4/33 (12.1%)		5/44 (11.4%)
Anorexia	2/33 (6.1%)		4/44 (9.1%)
Hyponatremia	4/33 (12.1%)		2/44 (4.5%)
Hypoglycemia	2/33 (6.1%)		3/44 (6.8%)
Hypokalemia	1/33 (3%)		3/44 (6.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/33 (12.1%)		7/44 (15.9%)
Back pain	2/33 (6.1%)		4/44 (9.1%)
Musculoskeletal and connective tissue disorders - Other, unknown	2/33 (6.1%)		3/44 (6.8%)
Nervous system disorders
Peripheral sensory neuropathy	2/33 (6.1%)		11/44 (25%)
Dizziness	5/33 (15.2%)		5/44 (11.4%)
Headache	4/33 (12.1%)		2/44 (4.5%)
Dysgeusia	2/33 (6.1%)		3/44 (6.8%)
Psychiatric disorders
Insomnia	3/33 (9.1%)		9/44 (20.5%)
Psychiatric disorders - Other, mood alteration	5/33 (15.2%)		7/44 (15.9%)
Renal and urinary disorders
Urinary frequency	1/33 (3%)		3/44 (6.8%)
Respiratory, thoracic and mediastinal disorders
Cough	5/33 (15.2%)		13/44 (29.5%)
Dyspnea	6/33 (18.2%)		9/44 (20.5%)
Respiratory, thoracic and mediastinal disorders - Other, unknown	3/33 (9.1%)		5/44 (11.4%)
Allergic rhinitis	3/33 (9.1%)		3/44 (6.8%)
Skin and subcutaneous tissue disorders
Rash	7/33 (21.2%)		16/44 (36.4%)
Hyperhidrosis	6/33 (18.2%)		4/44 (9.1%)
Pruritus	4/33 (12.1%)		3/44 (6.8%)
Skin and subcutaneous tissue disorders - Other	4/33 (12.1%)		1/44 (2.3%)
Vascular disorders
Hypertension	3/33 (9.1%)		3/44 (6.8%)
Flushing	1/33 (3%)		4/44 (9.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor can review/embargo results communications prior to public release for a period that is >60 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