Last updated: 11/03/2018 21:47:16
PGx7571: Pharmacogenetic Evaluation of FCGR Variation in patients treated with ofatumumab in study OMB115991
Clinicaltrials.gov ID
Not applicable
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: PGx7571: Pharmacogenetic Evaluation of FCGR Variation in patients treated with ofatumumab in study OMB115991
Trial description: GlaxoSmithKline (GSK) is developing ofatumumab (GSK1841157), an anti-CD20 monoclonal antibody (mAb), for the treatment of multiple oncology indications, including chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), indolent B-cell non-Hodgkin’s lymphoma (B-NHL) and diffuse large B-cell lymphoma (DLBCL), as well as non-oncology indications including multiple sclerosis and pemphigus vulgaris. Ofatumumab was approved by the Food and Drug Administration (FDA) in 2009 for the treatment of CLL subjects refractory to both alemtuzumab and fludarabine. Ofatumumab recognizes an epitope of the CD20 molecule distinct from the epitope of other CD20 mAbs, including the rituximab binding site, and induces cell lysis primarily through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). ADCC is regulated by activating and inhibiting Fc-gamma receptors (FCGRs). A significant body of research has been conducted and published regarding the association of functional variants in the activating FCGRs FCGR3A and FCGR2A with the efficacy of mAbs, including rituximab. The association differs by indication and treatment regimen (Mellor et al 2013), and the role of FCGR genetic variation on efficacy of ofatumumab is not known. The evaluation summarized in this document will contribute towards understanding the role of FCGR genetic variation in ofatumumab efficacy, and will be strengthened by data from additional clinical studies in the ofatumumab program. The objective of this study is to evaluate the association between FCGR3A rs396991 (V158F) and FCGR2A rs1801274 (H131R) and efficacy endpoints as measured by overall response rate (OR) complete response, and progression-free survival (PFS) in subjects with previously untreated or relapsed CLL treated with ofatumumab and bendamustine in study OMB115991.An additive genetic model will be applied based on the number of alleles (i.e. either FCGR3A 158V or FCGR2A 131H) to generate per-allele odds and hazard ratios, respectively, with 95% confidence intervals. An exact logistic regression model will be used to assess the association of genotype with OR or CR while a Cox proportional hazards model will be used to assess the association of genotype with PFS. One-tailed tests will be used to evaluate the hypotheses that FCGR3A 158V or FCGR2A 131H are associated with increased efficacy. Significance thresholds are set at p<0.05 for the primary objective of assessing the effect of FCGR3A V158F on OR in ofatumumab treated CLL subjects and at p<0.01 for all other objectives.
Primary purpose:
Not applicable
Trial design:
Not applicable
Masking:
Not applicable
Allocation:
Not applicable
Primary outcomes:
To assess the association of variants in Fc-gamma receptors with response to ofatumumab, measured as overall response.
Timeframe: N/A
Secondary outcomes:
To assess the association of variants in Fc-gamma receptors with response to ofatumumab, measured as progression free survival (PFS).
Timeframe: N/A
Interventions:
Enrollment:
1
Primary completion date:
Not applicable
Observational study model:
Cohort
Time perspective:
Retrospective
Clinical publications:
Not applicable
Medical condition
Leukaemia, Lymphocytic, Chronic
Product
ofatumumab
Collaborators
Not applicable
Study date(s)
September 2014 to October 2014
Type
Observational
Phase
Not applicable
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
none
- Provided written informed consent for PGx research when they enrolled in the clinical study OMB115991 and did not withdraw consent prior to PGx experiment AND
- Provided a blood sample for genotyping AND
- Did not provide written informed consent for PGx research when they enrolled in the clinical study OMB115991 or withdrew their PGx consent prior to genotyping being conducted OR
- Did not provide any or an adequate blood sample for genotyping OR
Inclusion and exclusion criteria
Inclusion criteria:
- Provided written informed consent for PGx research when they enrolled in the clinical study OMB115991 and did not withdraw consent prior to PGx experiment AND
- Provided a blood sample for genotyping AND
- Successfully genotyped for at least one genetic marker under study AND
- Valid clinical data available
Exclusion criteria:
- Did not provide written informed consent for PGx research when they enrolled in the clinical study OMB115991 or withdrew their PGx consent prior to genotyping being conducted OR
- Did not provide any or an adequate blood sample for genotyping OR
- Failed genotyping OR
- Did not have valid clinical data available
Trial location(s)
This study does not involve prospective enrollment of participants.
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2014-13-10
Plain language summaries
Not applicable. GSK’s transparency policy provides for Plain Language Summaries for Interventional studies.
Additional information about the trial
Not applicable
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