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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01110031




Registration number
NCT01110031
Ethics application status
Date submitted
22/04/2010
Date registered
23/04/2010
Date last updated
13/11/2017

Titles & IDs
Public title
Ofatumumab Cardiac Repolarization (QTc) Study in Fludarabine-Refractory Chronic Lymphocytic Leukemia Subjects
Scientific 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
Secondary ID [1] 0 0
112855
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukaemia, Lymphocytic, Chronic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Ofatumumab

Experimental: Treatment - Six months treatmet with ofatumumab will be given to subjects with chronic lymphocytic leukemia.


Other interventions: Ofatumumab
Anti-CD20 monoclonal antibody
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cardiac Repolarization (Fredericia's QTc)
Timepoint [1] 0 0
25-week ofatumumab treatment period
Secondary outcome [1] 0 0
Plasma concentrations of ofatumumab and electrocardiogram (ECG) parameters
Timepoint [1] 0 0
25-week ofatumumab treatment period
Secondary outcome [2] 0 0
Vital signs, weight, adverse events
Timepoint [2] 0 0
25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion
Secondary outcome [3] 0 0
Flow cytometry
Timepoint [3] 0 0
25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion
Secondary outcome [4] 0 0
Cytokine, chemokine, human anti-human antibodies
Timepoint [4] 0 0
25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Other
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/05/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/06/2012
Sample size
Target
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
New Zealand
State/province [2] 0 0
Auckland
Country [3] 0 0
New Zealand
State/province [3] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01110031
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01110031