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A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia

Phase 2
20 Years
Open (Enrolling)
Leukaemia, Lymphocytic, Chronic

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Trial Information

A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia

This is an open-label study to evaluate tolerability, safety, efficacy and pharmacokinetic
profile of ofatumumab in combination with chlorambucil in Japanese patients with previously
untreated Chronic Lymphocytic Leukemia (CLL). Ofatumumab will be infused intravenously at
Day 1 (300 mg) and Day 8 (1000 mg) in the first 28-day cycle, followed by infusions of 1000
mg at the first day of each 28-day cycle. Chlorambucil will be given 10 mg/m2 at Day 1-7 in
each 28-day cycle.

The primary objectives are to evaluate tolerability and overall response rate (ORR) of
ofatumumab with chlorambucil for previously untreated (frontline) CLL.

Secondary objectives include to evaluate complete remission (CR) rate, progression free
survival (PFS), overall survival (OS), time to response, duration of response, time to next
therapy, incidence and severity of adverse events and serious adverse events, incidences of
grade 3 and 4 infections and myelosuppression (anemia, neutropenia, thrombocytopenia), and
pharmacokinetics of ofatumumab and chlorambucil.

Inclusion Criteria:

- Diagnosis of CLL defined by : Circulating B lymphocytes ≥5,000 /μL AND Flow cytometry
confirmation of immunophenotype with CD5, CD19, CD20, and CD23 prior to Visit 2.

- Considered inappropriate for fludarabine-based therapy

- Active disease and indication for treatment based on modified NCI-WG guidelines
defined by presenting at least any one of the following conditions :

Evidence of progressive marrow failure as manifested by development or worsening of anemia
and/or thrombocytopenia.

Massive (i.e. at least 6 cm below the left costal margin) or progressive or symptomatic

Massive nodes (i.e. at least 10 cm in longest diameter) or progressive or symptomatic

Progressive lymphocytosis with an increase of more than 50% over a two month period or an
lymphocyte doubling time of less than 6 months.

A minimum of any one of the following disease-related symptoms must be present : a)
Unintentional Weight loss ≥ 10% within the previous six months ; b) Fevers >38.0 degree C
for ≥ 2 weeks without evidence of infection ; or c) Night sweats for more than 1 month
without evidence of infection.

- Not been previously treated for CLL (prior autoimmune hemolytic anemia treatment

- ECOG Performance Status of 0-2.

- Life expectancy of at least 6 months, in the opinion of the investigator.

- Age ≥ 20 years.

- Signed written informed consent prior to performing any study-specific procedures.

- Patients possible to stay at the trial site for at least two days (the day of the
first infusion and a subsequent day).

Exclusion Criteria:

- Prior immuno- or chemotherapy for CLL or small lymphocytic lymphoma (SLL) with any
agent except corticosteroids used to treat autoimmune hemolytic anemia.

- Previous autologous or allogeneic stem cell transplantation.

- Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy > 100
mg/day equivalent to hydrocortisone, or chemotherapy.

- Known transformation of CLL (e.g. Richter).

- Known CNS involvement of CLL.

- Chronic or current active infectious disease requiring systemic antibiotics,
antifungal, or antiviral treatment such as, but not limited to, chronic renal
infection, chronic chest infection with bronchiectasis, tuberculosis and active
Hepatitis C.

- Other past or current malignancy. Subjects who have been free of malignancy for at
least 5 years, or have a history of completely resected non-melanoma skin cancer, or
successfully treated in situ carcinoma are eligible.

- Clinically significant cardiac disease including unstable angina, acute myocardial
infarction within 6 months prior to screening (Visit 1), congestive heart failure,
and arrhythmia requiring therapy, with the exception of extra systoles or minor
conduction abnormalities.

- History of significant cerebrovascular disease or event with significant symptoms or

- Glucocorticoid use, unless given in doses ≤ 100 mg/day hydrocortisone (or equivalent
dose of other glucocorticoid) for <7 days for exacerbations other than CLL (e.g.

- Known HIV positive.

- Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In
addition, if negative for HBsAg but HBcAb and/or HBsAb positive, an HBV DNA test will
be performed and if positive the subject will be excluded.

- Screening laboratory values :

Creatinine > 2.0 times upper normal limit (unless normal creatinine clearance). Total
bilirubin > 2.0 times upper normal limit (unless due to Gilbert's syndrome).

Alanine transaminase (ALT) > 3.0 times upper normal limit.

- Previous treatment or known or suspected hypersensitivity to ofatumumab that in the
opinion of the investigator or medical monitor is a contraindication to their
participation in the present study.

- 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, treatment with
any anti-CD20 monoclonal antibody within 3 months of Visit 1, or participation in any
other interventional clinical study. Note: Participation in any other interventional
clinical study after disease progression during post PD-follow-up is permitted.

- Known or suspected inability to comply with study protocol.

- Lactating women, women with a positive pregnancy test at Visit 1 or women (of
childbearing potential) as well as men with partners of childbearing potential, who
are not willing to use adequate contraception from study start through one year
following last treatment dose. Adequate contraception is defined as oral hormonal
birth control, intrauterine device, male partner sterilization (if male partner is
sole partner for that subject) and the double barrier method (condom or occlusive cap
plus spermicidal agent).

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

Number of subjects who develop toxicity requiring discontinuation from study treatment during Cycle 1

Outcome Time Frame:

Up to Week 4

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



Japan: Pharmaceuticals and Medical Devices Agency

Study ID:




Start Date:

April 2012

Completion Date:

August 2014

Related Keywords:

  • Leukaemia, Lymphocytic, Chronic
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid