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

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.

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.