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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT01110031

Collaborator

(none)

Enrollment

Locations

Arm

25.5

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukaemia, Lymphocytic, Chronic	Biological: Ofatumumab	Phase 1

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

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

Actual Study Start Date :

May 13, 2010

Actual Primary Completion Date :

Apr 12, 2012

Actual Study Completion Date :

Jun 26, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Six months treatmet with ofatumumab will be given to subjects with chronic lymphocytic leukemia.	Biological: Ofatumumab Anti-CD20 monoclonal antibody Other Names: Arzerra

Arm

Intervention/Treatment

Experimental: Treatment

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

Biological: Ofatumumab

Anti-CD20 monoclonal antibody

Other Names:

Arzerra

Outcome Measures

Primary Outcome Measures

Cardiac Repolarization (Fredericia's QTc) [25-week ofatumumab treatment period]
ECGs are collected in triplicate during the study to assess QTc effect.

Secondary Outcome Measures

Plasma concentrations of ofatumumab and electrocardiogram (ECG) parameters [25-week ofatumumab treatment period]
The pharmacokinetic results will be correlated to ECG findings to determine if drug concentrations relate to any ECG effects.
Vital signs, weight, adverse events [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.
Flow cytometry [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
Cytokine, chemokine, human anti-human antibodies [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	La Jolla	California	United States	92093
2	GSK Investigational Site	Randwick	New South Wales	Australia	2031
3	GSK Investigational Site	Auckland		New Zealand	1150
4	GSK Investigational Site	Christchurch		New Zealand	8011