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

NCT ID: NCT01110031

Last Updated: 2017-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-13
• Study Completion Date: 2012-06-26

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.

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).

Conditions

Leukaemia, Lymphocytic, Chronic

Keywords

Chronic lymphocytic leukemia; Cardiac Repolarization (QTc)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Treatment

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

Group Type: EXPERIMENTAL

Ofatumumab

Intervention Type: BIOLOGICAL

Anti-CD20 monoclonal antibody

Interventions

Ofatumumab

Anti-CD20 monoclonal antibody

Intervention Type: BIOLOGICAL

Other Intervention Names

Arzerra

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

La Jolla, California, United States

GSK Investigational Site

Randwick, New South Wales, Australia

GSK Investigational Site

Auckland, , New Zealand

GSK Investigational Site

Christchurch, , New Zealand

Countries

United States; Australia; New Zealand

References

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.

Reference Type: DERIVED

PMID: 25103870 (View on PubMed)

Other Identifiers

112855

Identifier Type: -

Identifier Source: org_study_id