Leukaemia, Lymphocytic, ChronicPhase 1NCT01110031
Ofatumumab Cardiac Repolarization (QTc) Study in Fludarabine-Refractory Chronic Lymphocytic Leukemia Subjects
A Phase 1 study testing Ofatumumab in people with Leukaemia, Lymphocytic, Chronic, run by GlaxoSmithKline at 4 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukaemia, Lymphocytic, Chronic
- What is being tested?
- Ofatumumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 13 May 2010to 26 Jun 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
New Zealand2 sites
GSK Investigational Site
Auckland, 1150
GSK Investigational Site
Christchurch, 8011
United States1 site
GSK Investigational Site
La Jolla, California, 92093
About this study
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
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.
Read the 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
- Being tested
- Ofatumumab
- Keywords
- Chronic lymphocytic leukemia, Cardiac Repolarization (QTc)
- Medical subject headings
- Leukemia, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OfatumumabBiological
Also called Arzerra
Anti-CD20 monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Six months treatmet with ofatumumab will be given to subjects with chronic lymphocytic leukemia. Receives: Biological: Ofatumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac Repolarization (Fredericia's QTc)
ECGs are collected in triplicate during the study to assess QTc effect.
Measured: 25-week ofatumumab treatment period
Secondary outcomes (4)
Plasma concentrations of ofatumumab and electrocardiogram (ECG) parameters
The pharmacokinetic results will be correlated to ECG findings to determine if drug concentrations relate to any ECG effects.
Measured: 25-week ofatumumab treatment period
Vital signs, weight, adverse events
Safety and tolerability of ofatumumab therapy will be determined by analysing changes in vital signs, weight, or development of adverse events.
Measured: 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion
Flow cytometry
Efficacy of ofatumumab therapy will be measured by the number of CD20 positive cells in the blood
Measured: 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion
Cytokine, chemokine, human anti-human antibodies
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.
Measured: 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2010 (estimated)
- Study start13 May 2010
- Primary completion12 Apr 2012
- Study completion26 Jun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Leukaemia, Lymphocytic, ChronicStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01110031
- Sponsor's protocol ID
- 112855
- Status last verified
- Nov 2017
- First submitted
- 22 Apr 2010
- Last updated
- 13 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 25103870
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01110031
- Acronym / sponsor ID
- 112855
- Conditions
- Leukaemia, Lymphocytic, Chronic
- Keywords
- Chronic lymphocytic leukemia, Cardiac Repolarization (QTc)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 13 May 2010 (actual)
- Primary completion
- 12 Apr 2012 (actual)
- Study completion
- 26 Jun 2012 (actual)
- First posted
- 23 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Biological: OfatumumabSix months treatmet with ofatumumab will be given to subjects with chronic lymphocytic leukemia. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OfatumumabAlso: ArzerraAnti-CD20 monoclonal antibody | Biological | Treatment |
Primary outcome
Cardiac Repolarization (Fredericia's QTc)
Time frame: 25-week ofatumumab treatment period
ECGs are collected in triplicate during the study to assess QTc effect.
4 secondary outcomes
Plasma concentrations of ofatumumab and electrocardiogram (ECG) parameters
Time frame: 25-week ofatumumab treatment period
Vital signs, weight, adverse events
Time frame: 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion
Flow cytometry
Time frame: 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion
Cytokine, chemokine, human anti-human antibodies
Time frame: 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2017.
- Derived from this study: PubMed 25103870Jewell 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.
- Results for study 112855 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ofatumumab in people with Leukaemia, Lymphocytic, Chronic, run by GlaxoSmithKline at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in New Zealand, United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiac Repolarization (Fredericia's QTc) (time frame: 25-week ofatumumab treatment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01110031, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2017.