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Ofatumumab Cardiac Repolarization (QTc) Study in Fludarabine-Refractory Chronic Lymphocytic Leukemia Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01110031
First received: April 22, 2010
Last updated: June 28, 2012
Last verified: May 2012
History of Changes
  Purpose

Ofatumumab is a fully-human monoclonal antibody that exhibits high binding affinity to an antigen on the surface of B lymphocytes. Antigen engagement by ofatumumab results in maximal B-cell killing through complement-dependent cytotoxicity and antigen-dependent cellular cytotoxicity in both antigen high- and low-expressing cells. Recent research has shown that ofatumumab-dependent B-cell depletion provides clinical benefit to subjects with CD20-positive cancers such as chronic lymphocytic leukemia (CLL). The purpose of the current study is to assess the impact of ofatumumab on electrocardiographic parameters with particular focus on cardiac repolarization (QTc interval duration) in subjects with refractory CLL. Subjects enrolled in this open-label, single-arm trial will receive ofatumumab at the highest clinical dose (2000 mg) studied or planned for study. Ofatumumab will be administered as eight weekly intravenous (IV) infusions followed by four monthly infusions, beginning in Week 13, across a 25-week treatment period. Cardiovascular effects will be evaluated during treatment through routine 12-lead electrocardiographic (ECG) monitoring. The pharmacokinetic relationship between plasma concentration of ofatumumab and its effect on QTc interval duration will be examined. Specifically, ECG assessments will be collected in triplicate at baseline, at the time of maximum ofatumumab concentrations periodically on-therapy, and at the end of treatment. After completion of the final ofatumumab infusion, subjects will continue to be followed for safety and efficacy for six months relative to the last ofatumumab dose.


Condition Intervention Phase
Leukaemia, Lymphocytic, Chronic
 Biological: Ofatumumab
 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: An Open-Label, Single-Arm, Phase I Study to Evaluate the Effect of Ofatumumab on Cardiac Repolarization (QTc Duration) in Patients With Fludarabine-Refractory B-cell Chronic Lymphocytic Leukemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Cardiac Repolarization (Fredericia's QTc) [ Time Frame: 25-week ofatumumab treatment period ] [ Designated as safety issue: No ]
    ECGs are collected in triplicate during the study to assess QTc effect.


Secondary Outcome Measures:
  • Plasma concentrations of ofatumumab and electrocardiogram (ECG) parameters [ Time Frame: 25-week ofatumumab treatment period ] [ Designated as safety issue: No ]
    The pharmacokinetic results will be correlated to ECG findings to determine if drug concentrations relate to any ECG effects.

  • Vital signs, weight, adverse events [ Time Frame: 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion ] [ Designated as safety issue: No ]
    Safety and tolerability of ofatumumab therapy will be determined by analysing changes in vital signs, weight, or development of adverse events.

  • Flow cytometry [ Time Frame: 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion ] [ Designated as safety issue: No ]
    Efficacy of ofatumumab therapy will be measured by the number of CD20 positive cells in the blood

  • Cytokine, chemokine, human anti-human antibodies [ Time Frame: 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion ] [ Designated as safety issue: No ]
    Effect of ofatumumab on circulating biomarkers in refractory Chronic Lymphocytic Leukemia (CLL) subjects will be determined by measuring changes in the cytokine, chemokine, human anti-human antibody levels.


Enrollment: 13
Study Start Date: May 2010
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Six months treatmet with ofatumumab will be given to subjects with chronic lymphocytic leukemia.
 Biological: Ofatumumab
Anti-CD20 monoclonal antibody
Other Name: Arzerra

Detailed Description:

The purpose of this trial is to assess the impact of ofatumumab on electrocardiographic parameters with particular focus on cardiac repolarization (QTc interval duration) in subjects with refractory Chronic Lymphocytic Leukemia (CLL).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL).
  • Active CLL disease and indication for treatment.
  • Previous treatment with fludarabine-containing treatment that did not achieve at least a partial response or, disease progression occurred in responders within six months of the last dose of a fludarabine-containing treatment regimen.
  • Fully active at a minimum, or fully capable of self-care and up and about more than 50% of waking hours.
  • Age 18 years or older.
  • Signed written informed consent.
  • Acceptable levels of laboratory chemistry tests of potassium and magnesium.
  • Males and female subjects must agree to use contraception (if fertile) from the time of the first dose of study medication until one year following last dose of ofatumumab.

Exclusion Criteria:

  • Any abnormal electrocardiogram (ECG) or cardiac conduction findings .
  • Certain heart problems, chronic infections, or serious significant diseases.
  • Known transformation of CLL.
  • CLL central nervous sytem involvement.
  • Abnormal/inadequate blood values, liver, or kidney function.
  • Past or current malignancy besides CLL, unless you have been free of malignancy for at least two years, have a history of completely resected non-melanoma skin cancer, or have been successfully treated.
  • Lactating women or women with a positive pregnancy test.
  • Use of medications known to prolong the heart rhythm.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01110031

Locations
United States, California
GSK Investigational Site
La Jolla, California, United States, 92093
Australia, New South Wales
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
New Zealand
GSK Investigational Site
Auckland, New Zealand, 1150
GSK Investigational Site
Christchurch, New Zealand, 8011
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01110031     History of Changes
Other Study ID Numbers: 112855
Study First Received: April 22, 2010
Last Updated: June 28, 2012
Health Authority: New Zealand: Medsafe
United States: Food and Drug Administration
Australia: Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:
Chronic lymphocytic leukemia
Cardiac Repolarization (QTc)

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
 Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013