Ignite Creation Date:
2024-05-06 @ 3:26 AM
Last Modification Date:
2024-10-26 @ 11:33 AM
Study NCT ID:
NCT02280785
Status:
COMPLETED
Last Update Posted:
2018-09-06
First Post:
2014-10-05
Brief Title:
Brentuximab Vedotin for RelapsedRefractory CD30-positive Non-Hodgkin Lymphomas
Sponsor:
Samsung Medical Center
Organization:
Samsung Medical Center
Study Overview
Official Title:
A Phase II Study of Brentuximab Vedotin for RelapsedRefractory CD30-positive Non-Hodgkin Lymphomas Other Than Anaplastic Large Cell Lymphoma
Status:
COMPLETED
Status Verified Date:
2018-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BRAN
Brief Summary:
Brentuximab vedotin is an antibody-drug conjugate targeting CD30 one of surface antigens expressed in lymphoma cells Fanale MA et al reported the results of a phase I study with weekly dosing of brentuximab vedotin in patients with relapsedrefractory CD30-positive hematologic malignancies Clin Cancer Res 2012 showed tumor regression in 85 of patients Thus the overall objective response rate was 59 2444 including 34 n 14 of complete remissions This study mainly included Hodgkin lymphoma n 38 and anaplastic large cell lymphoma n 5 However its efficacy in other types of NHL has never been reported although this study enrolled one patient with peripheral T-cell lymphoma not otherwise specified PTCL-NOS
CD30 TNFRSF8 is a transmembrane glycoprotein of the tumor necrosis factor receptor TNFR superfamily and it is involved in signal transduction via the activation of the NF-κB pathway and the mitogen-activated protein kinases MAPKs ultimately modulating cell growth proliferation and apoptosis CD30 is a non-lineage-specific activation marker expressed by scattered B and T immunoblasts In addition a subset of cases in virtually all T-cell lymphoma entities may also express CD30 but at variable and generally lower levels In fact a recent study in 22 patients with extranodal NKT-cell lymphoma showed 75 of positive rate of CD30 expression 75 Moreover CD30 expression was also documented in the tumor sample of EB virus positive diffuse large B-cell lymphomas EBV DLBCL of the elderly 289 1138 Therefore Brentuximab vedotin may have potential benefits for patients with CD30-positive NHL other than anaplastic large cell lymphoma such as CD30-positive PTCLs NOS Considering the role of CD30 in signal transduction pathway associated with tumor growth and proliferation its expression may be associated with tumor aggressiveness In accordance with this it is more likely that relapse or refractory NHLs may have CD30 expression and the potential benefits of this promising agent as a salvage therapy deserve to be further investigated in these patients who have high risk of treatment failure Thus we designed a phase II study for relapsed or refractory NHL patients This study is to explore the safety and activity of dosing once every 3 weeks of Brentuximab vedotin in patients with relapsed or refractory CD30-positive NHL other than anaplastic large cell lymphoma
CD30 TNFRSF8 is a transmembrane glycoprotein of the tumor necrosis factor receptor TNFR superfamily and it is involved in signal transduction via the activation of the NF-κB pathway and the mitogen-activated protein kinases MAPKs ultimately modulating cell growth proliferation and apoptosis CD30 is a non-lineage-specific activation marker expressed by scattered B and T immunoblasts In addition a subset of cases in virtually all T-cell lymphoma entities may also express CD30 but at variable and generally lower levels In fact a recent study in 22 patients with extranodal NKT-cell lymphoma showed 75 of positive rate of CD30 expression 75 Moreover CD30 expression was also documented in the tumor sample of EB virus positive diffuse large B-cell lymphomas EBV DLBCL of the elderly 289 1138 Therefore Brentuximab vedotin may have potential benefits for patients with CD30-positive NHL other than anaplastic large cell lymphoma such as CD30-positive PTCLs NOS Considering the role of CD30 in signal transduction pathway associated with tumor growth and proliferation its expression may be associated with tumor aggressiveness In accordance with this it is more likely that relapse or refractory NHLs may have CD30 expression and the potential benefits of this promising agent as a salvage therapy deserve to be further investigated in these patients who have high risk of treatment failure Thus we designed a phase II study for relapsed or refractory NHL patients This study is to explore the safety and activity of dosing once every 3 weeks of Brentuximab vedotin in patients with relapsed or refractory CD30-positive NHL other than anaplastic large cell lymphoma
Detailed Description:
The principal investigator use a Simon two-stage minimax design based on overall response rates Overall disease control rates will be calculated as the percent of patients that have confirmed complete response CR or partial response PR or stable disease SD by radiographic response including CT andor PET scans We assume a P0 as 20 and designate a target rate P1 as 40 Under the error probabilities α005 β020 eighteen patients will be enrolled in the first stage If overall disease control rate is 418 in the first stage this study will be stopped If not this study will recruit patients up to 33 considering 20 of drop out rate
Intent-to-treat analysis will be applied to all primary and secondary efficacy endpoints Response rate will be analyzed based on the response criteria according to Cheson 2007 Cheson BD et al J Clin Oncol 2007 25 5579-586 and data related to overall response rate will be analyzed by statistical analysis including Chi test to evaluate predictive factors for response to study drug
Overall rate of disease control CR PR and SD Progression-free survival Time between the date of treatment start and the date of death due to any cause or date of disease progression Up to 36months Data related to survival rate for all patients will be analyzed based on log-rank test by the Kaplan-Meier method
Intent-to-treat analysis will be applied to all primary and secondary efficacy endpoints Response rate will be analyzed based on the response criteria according to Cheson 2007 Cheson BD et al J Clin Oncol 2007 25 5579-586 and data related to overall response rate will be analyzed by statistical analysis including Chi test to evaluate predictive factors for response to study drug
Overall rate of disease control CR PR and SD Progression-free survival Time between the date of treatment start and the date of death due to any cause or date of disease progression Up to 36months Data related to survival rate for all patients will be analyzed based on log-rank test by the Kaplan-Meier method
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None