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Completed

NCT Number: NCT01110031

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

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.

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Key information

Conditions

Leukaemia, Lymphocytic, Chronic Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site, Randwick, New South Wales, Australia

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Ofatumumab

Biological

Anti-CD20 monoclonal antibody

Other names: Arzerra

Primary outcomes

  1. Cardiac Repolarization (Fredericia's QTc)

    Time frame: 25-week ofatumumab treatment period

    ECGs are collected in triplicate during the study to assess QTc effect.

Secondary outcomes

  1. Plasma concentrations of ofatumumab and electrocardiogram (ECG) parameters

    Time frame: 25-week ofatumumab treatment period

    The pharmacokinetic results will be correlated to ECG findings to determine if drug concentrations relate to any ECG effects.

  2. Vital signs, weight, adverse events

    Time frame: 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion

    Safety and tolerability of ofatumumab therapy will be determined by analysing changes in vital signs, weight, or development of adverse events.

  3. Flow cytometry

    Time frame: 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion

    Efficacy of ofatumumab therapy will be measured by the number of CD20 positive cells in the blood

  4. Cytokine, chemokine, human anti-human antibodies

    Time frame: 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion

    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.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study 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

Important dates

Study start
2010
Primary completion
2012
Study completion
2012
First posted
Apr 23, 2010
Registry last updated
Nov 13, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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