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

NCT01110031 | Completed Phase 1

• 1 other identifier: 112855
• Study Type: interventional
• Target: 12
• Locations: 3 countries
• Sites: 4

Brief Summary

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.

Conditions

Leukaemia, Lymphocytic, Chronic

Keywords

Chronic lymphocytic leukemia; Cardiac Repolarization (QTc)

Outcome Measures

Primary Outcomes (1)

• Cardiac Repolarization (Fredericia's QTc)

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

  25-week ofatumumab treatment period

Secondary Outcomes (4)

• Plasma concentrations of ofatumumab and electrocardiogram (ECG) parameters

  25-week ofatumumab treatment period

• Vital signs, weight, adverse events

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

• Flow cytometry

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

• Cytokine, chemokine, human anti-human antibodies

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

Study Arms (1)

Treatment

EXPERIMENTAL

Six months treatmet with ofatumumab will be given to subjects with chronic lymphocytic leukemia.

Biological: Ofatumumab

Interventions

Ofatumumab BIOLOGICAL

Anti-CD20 monoclonal antibody

Also known as: Arzerra

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

La Jolla, California, 92093, United States

Location

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

GSK Investigational Site

Auckland, 1150, New Zealand

Location

GSK Investigational Site

Christchurch, 8011, New Zealand

Location

Related Publications (1)

• Jewell RC, Laubscher K, Lewis E, Fang L, Gafoor Z, Carey J, McKeown A, West S, Wright O, Sedoti D, Dixon I, Hottenstein CS, Chan G. Assessment of the effect of ofatumumab on cardiac repolarization. J Clin Pharmacol. 2015 Jan;55(1):114-21. doi: 10.1002/jcph.376. Epub 2014 Aug 21.

  PMID: 25103870 DERIVED

Related Links

• Results for study 112855 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ofatumumab

Condition Hierarchy (Ancestors)

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

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2010
• First Posted: April 23, 2010
• Study Start: May 13, 2010
• Primary Completion: April 12, 2012
• Study Completion: June 26, 2012
• Last Updated: November 13, 2017

Record last verified: 2017-11

Locations

AU (1); NZ (2); US (1)