Ofatumumab for Initial Systemic Treatment of Indolent B-cell Lymphoma

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01239394
• Collaborator: Dana-Farber Cancer Institute (Other), Beth Israel Deaconess Medical Center (Other), GlaxoSmithKline (Industry)
• Enrollment: 43
• Locations: 3
• Arm: 1
• Actual Duration (Months): 51
• Patients Per Site: 14.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Ofatumumab is a drug that works by attaching to the CD20 molecule found on the surface of cancerous B cells, and then triggering the death of those cells. It is approved by the FDA for treatment of another B-cell cancer, chronic lymphocytic leukemia, and also has evidence of success in people who's B-cell lymphomas have relapsed after initial treatments. In this research study we are looking to see if ofatumumab is effective and safe in treating previously untreated B-cell NHL.

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma; Marginal Zone Lymphoma; Small Lymphocytic Lymphoma	Drug: ofatumumab	Phase 2

Detailed Description

• Participants will receive ofatumumab once a week for 8 weeks by intravenous infusion (Days 1, 8, 15, 22, 29, 36, 43, and 50).

• Participants will be seen weekly during the 8 week treatment period and will have the following tests and procedures performed: Blood tests, performance status and physical examination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial Ofatumumab for Initial Systemic Treatment of Indolent B-cell Lymphoma
• Actual Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Other: ofatumumab single-arm, open-label, interventional	Drug: ofatumumab; Weekly infusion for 8 weeks; Other Names: GSK1841157 HuMax-CD20

Outcome Measures

Primary Outcome Measures

1. Efficacy: Complete Response Rate (CRR) [1-month post-treatment]

   Evaluate clinical efficacy of ofatumumab in previously untreated indolent B-cell lymphomas, as measured by complete response rate (CRR). Complete response = all previously enlarged fluorodeoxyglucose (FDG)-avid or positron emission tomography (PET)-positive lymph nodes regressed to normal size (<=1.5 cm in greatest diameter)

Secondary Outcome Measures

1. Overall Response Rate (ORR) [1-month post-treatment]

   Evaluate clinical efficacy of ofatumumab in previously untreated indolent B-cell lymphomas, as measured by overall response rate (ORR). Overall response = Complete response (CR) + Partial response (PR) CR = all previously enlarged fluorodeoxyglucose (FDG)-avid or positron emission tomography (PET)-positive lymph nodes regressed to normal size (<=1.5cm in greatest diameter) PR = >=50% decrease in SPD of up to six largest dominant masses, no increase in size of other nodes; FDG avid or PET positive before therapy, one or more nodes PET positive at previously involved site, or variably FDG avid or PET negative with regression at CT

2. Progression-free Survival (PFS) [12 months]

   Percentage of patients with progression-free survival during 12 months post-treatment progression-free survival: patients live with the disease, but it does not get worse

3. Toxicity: Infusion Reactions, Grade 3-4 Infections, and Neutropenia [2 years]

   Evaluate safety of ofatumumab monotherapy in this patient population Toxicities are graded 1 (mild), 2 (moderate), 3 (severe), and 4 (life-threatening)

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed indolent CD20+B-cell NHL of the following histologies: follicular lymphoma, grades 1-2; Marginal zone lymphoma (extranodal, nodal or splenic); small lymphocytic lymphoma; low-grade B-cell lymphoma not otherwise specified with CD20+ expression

• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 20mm or greater CT scan or MRI

• No previous chemotherapy, antibody therapy or radioimmunotherapy for this disease. Patients previously treated with external beam radiation alone are eligible

• 18 years of age or older

• Life expectancy of greater than 3 months

• ECOG Performance status of 0, 1 or 2

• Organ function as described in the protocol

• Women of child-bearing potential and men must agree so use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria:

• Prior chemotherapy, antibody therapy or radioimmunotherapy for lymphoma

• Participants may not be receiving any other investigational agent

• Participants with known brain metastases

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ofatumumab

• Prior exposure to ofatumumab or other targeted anti-CD20 therapies including rituximab

• Known HIV positivity

• Positive serology for Hepatitis B

• Positive serology for Hepatitis C

• Participants who are candidates for curative radiotherapy, unless radiation therapy is considered too toxic (as in abdominal disease), or is refused by the patient

• New York Heart Association Classification III of IV heart disease

• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection that is not optimally treated with antibiotics, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant or breastfeeding women

• History of a different malignancy are ineligible except for the following circumstances: Individuals with a history of other malignancy are eligible if they have been disease-free for at least one year and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible even if diagnosed and treated within the past 1 year: localized prostate cancer, prostate cancer with elevated PSA but no measurable disease on CT scans or bone scan, cervical cancer in situ, breast ductal carcinoma in situ and non-melanoma skin cancers.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Massachusetts General Hospital
• Dana-Farber Cancer Institute
• Beth Israel Deaconess Medical Center
• GlaxoSmithKline

Investigators

• Principal Investigator: Jeremy S. Abramson, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeremy Abramson, MD, Director, Lymphoma Program, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01239394
• Other Study ID Numbers: 10-271
• First Posted: Nov 11, 2010
• Last Update Posted: Oct 18, 2017
• Last Verified: Sep 1, 2017

• Keywords provided by Jeremy Abramson, MD, Director, Lymphoma Program, Massachusetts General Hospital: NHL; ofatumumab
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell; Ofatumumab

Study Results

Participant Flow

Pre-assignment Detail	The number enrolled (43) and number starting study (42) do not match because one patient never began study treatment due to an acute stroke prior to any study treatment.

Arm/Group Title	Ofatumumab
Arm/Group Description	single-arm, open-label, interventional ofatumumab: Weekly infusion for 8 weeks
Period Title: Overall Study
STARTED	42
COMPLETED	41
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Ofatumumab
Arm/Group Description	single-arm, open-label, interventional ofatumumab: Weekly infusion for 8 weeks
Overall Participants	42
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64.4
Sex: Female, Male (Count of Participants)
Female	18 42.9%
Male	24 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4.8%
Not Hispanic or Latino	35 83.3%
Unknown or Not Reported	5 11.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 2.4%
White	36 85.7%
More than one race	2 4.8%
Unknown or Not Reported	3 7.1%
Region of Enrollment (participants) [Number]
United States	42 100%
Lymphoma type (Count of Participants)
Follicular	28 66.7%
Marginal zone	4 9.5%
Small lymphocytic	10 23.8%

Outcome Measures

1. Primary Outcome

Title	Efficacy: Complete Response Rate (CRR)
Description	Evaluate clinical efficacy of ofatumumab in previously untreated indolent B-cell lymphomas, as measured by complete response rate (CRR). Complete response = all previously enlarged fluorodeoxyglucose (FDG)-avid or positron emission tomography (PET)-positive lymph nodes regressed to normal size (<=1.5 cm in greatest diameter)
Time Frame	1-month post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab
Arm/Group Description	single-arm, open-label, interventional ofatumumab: Weekly infusion for 8 weeks
Measure Participants	41
Number [percentage of patients]	9.5

2. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Evaluate clinical efficacy of ofatumumab in previously untreated indolent B-cell lymphomas, as measured by overall response rate (ORR). Overall response = Complete response (CR) + Partial response (PR) CR = all previously enlarged fluorodeoxyglucose (FDG)-avid or positron emission tomography (PET)-positive lymph nodes regressed to normal size (<=1.5cm in greatest diameter) PR = >=50% decrease in SPD of up to six largest dominant masses, no increase in size of other nodes; FDG avid or PET positive before therapy, one or more nodes PET positive at previously involved site, or variably FDG avid or PET negative with regression at CT
Time Frame	1-month post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab
Arm/Group Description	single-arm, open-label, interventional ofatumumab: Weekly infusion for 8 weeks
Measure Participants	41
Number [percentage of patients]	52

3. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Percentage of patients with progression-free survival during 12 months post-treatment progression-free survival: patients live with the disease, but it does not get worse
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab
Arm/Group Description	single-arm, open-label, interventional ofatumumab: Weekly infusion for 8 weeks
Measure Participants	41
Number (95% Confidence Interval) [percentage of patients]	86

4. Secondary Outcome

Title	Toxicity: Infusion Reactions, Grade 3-4 Infections, and Neutropenia
Description	Evaluate safety of ofatumumab monotherapy in this patient population Toxicities are graded 1 (mild), 2 (moderate), 3 (severe), and 4 (life-threatening)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab
Arm/Group Description	single-arm, open-label, interventional ofatumumab: Weekly infusion for 8 weeks
Measure Participants	42
Infusion reactions (grade 1-2)	22 52.4%
Infusion reactions (grade 3)	7 16.7%
Infections (grade 3-4)	1 2.4%
Neutropenia (grade 3-4)	0 0%

Adverse Events

Arm/Group Title	Ofatumumab
Arm/Group Description	single-arm, open-label, interventional ofatumumab: Weekly infusion for 8 weeks
All Cause Mortality
	Ofatumumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ofatumumab
	Affected / at Risk (%)	# Events
Total	2/42 (4.8%)
Eye disorders
Photophobia	1/42 (2.4%)	1
General disorders
Fever	1/42 (2.4%)	1
Nervous system disorders
Vestibular Schwannoma	1/42 (2.4%)	1
Headache	1/42 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/42 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Ofatumumab
	Affected / at Risk (%)	# Events
Total	38/42 (90.5%)
Blood and lymphatic system disorders
Anemia	4/42 (9.5%)	6
Gastrointestinal disorders
Nausea	9/42 (21.4%)	12
Diarrhea	6/42 (14.3%)	8
Abdominal pain	5/42 (11.9%)	7
Constipation	4/42 (9.5%)	4
Dyspepsia	3/42 (7.1%)	3
Vomiting	3/42 (7.1%)	3
General disorders
Fatigue	19/42 (45.2%)	21
Infusion related react	6/42 (14.3%)	6
Immune system disorders
Allergic reaction	28/42 (66.7%)	30
Infections and infestations
Bladder infection	3/42 (7.1%)	3
Investigations
Platelet count decrease	5/42 (11.9%)	5
Blood bilirubin increase	4/42 (9.5%)	4
Alanine aminotransferase	3/42 (7.1%)	5
Neutrophil count decrease	3/42 (7.1%)	3
Musculoskeletal and connective tissue disorders
Back pain	4/42 (9.5%)	5
Arthralgia	4/42 (9.5%)	4
Pain in extremity	4/42 (9.5%)	4
Nervous system disorders
Headache	7/42 (16.7%)	7
Dizziness	3/42 (7.1%)	3
Psychiatric disorders
Insomnia	5/42 (11.9%)	5
Anxiety	3/42 (7.1%)	3
Respiratory, thoracic and mediastinal disorders
Cough	6/42 (14.3%)	6
Dyspnea	5/42 (11.9%)	5
Skin and subcutaneous tissue disorders
Pruritus	5/42 (11.9%)	6
Rash maculo-papular	4/42 (9.5%)	5
Skin and subcutaneous	4/42 (9.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.