Last updated: 11/03/2018 22:12:02
PGx7597: Meta-analyses of data from FCGR PGx evaluations of ofatumumab CLL studies
Clinicaltrials.gov ID
Not applicable
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: PGx7597: Meta-analyses of data from FCGR PGx evaluations of ofatumumab CLL studies
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), and progression-free survival (PFS) in subjects with CLL treated with ofatumumab in studies OMB110911, OMB114242 and OMB115991.Within each study for subjects treated with ofatumumab (OMB110911, OMB114242, 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 while a Cox proportional hazards model will be used to assess the association of genotype with PFS.Fixed effects meta-analysis will be used to assess the association between FCGR3A V158F and FCGR2A H131R and efficacy endpoints across studies. 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<0.017 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 treatment, measured as overall response.
Timeframe: N/A
Secondary outcomes:
To assess the association of variants in Fc-gamma receptors with response to ofatumumab or rituximab treatment, 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
Lymphoma, Large-Cell, Diffuse, Leukemia, Lymphocytic, Chronic, B-Cell
Product
ofatumumab
Collaborators
Not applicable
Study date(s)
November 2014 to November 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 studies OMB110911, OMB114242 and OMB115991 and did not withdraw consent prior to PGx experiment AND
- Were treated with ofatumumab AND
- Did not provide written informed consent for PGx research when they enrolled in the clinical studies OMB110911, OMB114242 and OMB115991 or withdrew their PGx consent prior to genotyping being conducted OR
- Were not treated with ofatumumab
Inclusion and exclusion criteria
Inclusion criteria:
- Provided written informed consent for PGx research when they enrolled in the clinical studies OMB110911, OMB114242 and OMB115991 and did not withdraw consent prior to PGx experiment AND
- Were treated with ofatumumab 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 studies OMB110911, OMB114242 and OMB115991 or withdrew their PGx consent prior to genotyping being conducted OR
- Were not treated with ofatumumab
- 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
2014-19-11
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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