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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01110031
Other study ID # 112855
Secondary ID
Status Completed
Phase Phase 1
First received April 22, 2010
Last updated November 8, 2017
Start date May 13, 2010
Est. completion date June 26, 2012

Study information

Verified date November 2017
Source GlaxoSmithKline
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 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.


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).


Recruitment information / eligibility

Status Completed
Enrollment 12
Est. completion date June 26, 2012
Est. primary completion date April 12, 2012
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Ofatumumab
Anti-CD20 monoclonal antibody

Locations

Country Name City State
Australia GSK Investigational Site Randwick New South Wales
New Zealand GSK Investigational Site Auckland
New Zealand GSK Investigational Site Christchurch
United States GSK Investigational Site La Jolla California

Sponsors (1)

Lead Sponsor Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  New Zealand, 

Outcome

Type Measure Description Time frame Safety issue
Primary Cardiac Repolarization (Fredericia's QTc) ECGs are collected in triplicate during the study to assess QTc effect. 25-week ofatumumab treatment period
Secondary 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. 25-week ofatumumab treatment period
Secondary 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. 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion
Secondary Flow cytometry Efficacy of ofatumumab therapy will be measured by the number of CD20 positive cells in the blood 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion
Secondary 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. 25-week ofatumumab treatment period plus 6-month follow-up after final ofatumumab infusion
See also
  Status Clinical Trial Phase
Completed NCT01453062 - Phase IV Observational Study in Chronic Lymphocytic Leukemia N/A
Completed NCT01077622 - A Phase I/II, a Single Arm, Open-label Study of Ofatumumab (GSK1841157) in Patients With Previously Treated Chronic Lymphocytic Leukemia Phase 2
Terminated NCT01039376 - Ofatumumab Maintenance Treatment vs No Further Treatment in Relapsed CLL Responding to Induction Therapy Phase 3
Active, not recruiting NCT01520922 - Ofatumumab Plus Bendamustine in Frontline and Relapsed Chronic Lymphocytic Leukaemia (CLL) Phase 2
Completed NCT00824265 - Ofatumumab Added to Fludarabine-Cyclophosphamide vs Fludarabine-Cyclophosphamide Combination in Relapsed Subjects With Chronic Lymphocytic Leukemia Phase 3
Completed NCT00349349 - HuMax-CD20 in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients Failing Fludarabine and Alemtuzumab Phase 2
Completed NCT00802737 - Efficacy and Safety of Ofatumumab Retreatment and Maintenance Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL) Phase 4
Completed NCT00410163 - Ofatumumab With Fludarabine and Cyclophosphamide in B-CLL Patients Phase 2
Terminated NCT00748189 - Ofatumumab + Chlorambucil vs Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia Phase 3
Completed NCT01563055 - A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia Phase 2