Ofatumumab as Front-Line Therapy in Treating Elderly Participants With Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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This phase II trial studies how well ofatumumab works as front-line therapy in treating elderly participants with chronic lymphocytic leukemia. Monoclonal antibodies, such as ofatumumab, may interfere with the ability of cancer cells to grow and spread.

Detailed Description
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PRIMARY OBJECTIVES I. To evaluate the overall response rate of ofatumumab in the upfront setting in elderly, unfit patients with chronic lymphocytic leukemia (CLL). SECONDARY OBJECTIVES: I. To determine the overall survival with ofatumumab in upfront setting in elderly, unfit CLL patients. II. To evaluate the complete response rate and time to progression to therapy of ofatumumab in elderly, unfit patients with CLL. III. To determine the plasma levels of ofatumumab in elderly, unfit patients. IV. To evaluate predictive capability of micro ribonucleic acid (RNA) (miRNAs) detection in plasma samples. OUTLINE: Participants receive ofatumumab intravenously (IV) over 4 hours once a week for 4 weeks, then monthly thereafter. Treatment continues for up to 12 months in the absence of disease progression or unacceptable toxicity.

Official Title
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Phase II Study of Ofatumumab as Front-Line Treatment in Elderly, Unfit Patients With Chronic Lymphocytic Leukemia (CLL)

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Biological: Ofatumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with chronic lymphocytic leukemia requiring treatment at the time of signing informed consent. Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status of 2-3 and a Cumulative Illness Rating Scale (CIRS) or Charlson co-morbidity score of 2 or higher. Creatinine < 2mg/dL. Estimated glomerular filtration rate (eGFR) more than 30cc/minute. Bilirubin < 2mg/dL. Patients with renal or liver dysfunction due to organ infiltration by lymphocytes may be eligible after discussion with the study chairman. Patients with Gilbert's syndrome are eligible. Exclusion Criteria: Patients with documented prolymphocytic leukemia (prolymphocytes more than 55% in the blood). Known positivity for human immunodeficiency virus (HIV). Hepatitis B (HB) defined as a positive test for hepatitis B surface antigen (HBsAg). In addition, if negative for HGsAg but hepatitis B core antibody (HBcAb) positive (regardless of HBsAb status), a HB deoxyribonucleic acid (DNA) test will be performed and if positive the subject will be excluded. Prior treatment for chronic lymphocytic leukemia. Concurrent chemotherapy, radiotherapy, or immunotherapy, including other monoclonal antibodies. Localized radiotherapy to an area not compromising bone marrow function does not apply. Patients with malignancies with indolent behavior such as prostate cancer treated with radiation or surgery can be enrolled in the study as long as they have a reasonable expectation to have been cured with the treatment modality received. Any serious medical condition, laboratory abnormality, or psychiatric illness that places the subject at unacceptable risk if he/she were to participate in the study. Any known hypersensitivity to ofatumumab or its components.

Ages Eligible for Study
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Minimum Age: 66 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (ofatumumab)<br>Participants receive ofatumumab IV over 4 hours once a week for 4 weeks, then monthly thereafter. Treatment continues for up to 12 months in the absence of disease progression or unacceptable toxicity. | Biological: Ofatumumab<br>* Given IV<br>* Other names: HuMax-CD20, 2F2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With a Response | Response = (complete response [CR] + partial response [PR]) per 2008 National Cancer Institute (NCI)-Working Group (WG) criteria. Complete Response (CR): Absence of disease signs/symptoms, normalization of peripheral blood and bone marrow. Partial Response (PR): At least 50 % reduction in disease signs/symptoms and normalization of peripheral blood. | Up to 3 years, 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Time from date of treatment start until the date of first objective documentation of disease-relapse. | Up to 3 years, 10 months | 
| Participants With a Complete Response (CR) | Complete Response (CR): Absence of disease signs/symptoms, normalization of peripheral blood and bone marrow. | Up to 3 years, 10 months |