Epigenetic Modulation in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
The purpose of this study is evaluate the response, safety and tolerability in subjects receiving the investigational drugs, RAD001 and LBH589.
Diffuse Large B-cell Lymphoma
Drug: RAD001 and LBH589 as a doublet
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study to Evaluate the Efficacy of Epigenetic Modulation in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)|
- Overall response rate [ Time Frame: From the start of combination therapy until a maximum of 2 years after completion of therapy ] [ Designated as safety issue: No ]Overall Response Rate is the number of participants with a partial and complete response assessed by the Updated Cheson criteria for lymphoma. A complete response is complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy and normalization of those biochemical abnormalities. If a subject has residual lesions on CT scan and the disease was FDG avid pre-treatment, then that subject will be considered to be in a complete response. Partial response is a greater than or equal to 50% decrease in the sum of the products of the greatest diameters of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease
- Assessment of association between observed response to RAD001 and LBH589 and the response predicted by molecular signatures developed in our pre-clinical model [ Time Frame: From the start of combination therapy until a maximum of 2 years after completion of therapy ] [ Designated as safety issue: No ]We will estimate the association of the molecular signature-predicted response to the doublet (CR+PR) with the observed response. All evaluable patients will be used in estimating response. The chi-square test with one-sided alpha of 0.10 will be used to test for the association between predicted and observed responses. Contingency tables will be used to present these associations.
- Summary of Adverse Events (AEs) [ Time Frame: From the time of first dose of study drug until 4 weeks after participant has stopped study drug ] [ Designated as safety issue: Yes ]Counts of participants who had adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose). National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) is used to assess severity. Relatedness to study drug is assessed by the investigator.
- Distribution of change across time of mTOR and HDAC-I inhibition from baseline until after the 1st 2 cycles of study drug in patients who received LBH and RAD. [ Time Frame: after 2 cycles of study therapy ] [ Designated as safety issue: No ]Serum markers will be measured on the first day of cycle 1 and on the first day of cycle 3. The distribution of change across time in a marker will be summarized.
- Evaluate the association of observed response to the doublet with the response predicted by molecular signatures for activated B cell like (ABC) DLBCL and for Germinal Center B cell like (GCB) DLBCL. [ Time Frame: up to 13 cycles of therapy ] [ Designated as safety issue: No ]Response rates seen in subjects with activated B cell like DLBCL and for Germinal center B cell like DLBCL will be reported and assessed to see if GCB is associated with improved outcomes compared to ABC in subjects with relapsed disease who have received RAD + LBH. We will estimate the association of the ABC and GCB with the observed response. All evaluable patients will be used in estimating response. The chi-square test with one-sided alpha of 0.10 will be used to test for the association between predicted and observed responses.
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||June 2018|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
This will be a prospective, non-randomized, un-blinded phase 2 efficacy trial using an mTOR inhibitor and a histone deacetylase (HDAC) inhibitor for epigenetic targeted therapies.
Subjects will receive RAD001 and LBH589 given in four to thirteen, 28-day cycles. Subjects with progressive disease will stop after 4 cycles. Subjects with stable disease or better after 4 cycles may receive up to 13 cycles. LBH will start at 20mg po on days M/W/F and RAD001 will start at 10mg po daily.
Treatment will be administered on an outpatient basis. Patients will be followed for up to 2 years after completion of therapy or until progression of disease or death.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00978432
|Contact: Peggy Alton, RN, BSNfirstname.lastname@example.org|
|Contact: Patricia Davis, RNemail@example.com|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Principal Investigator: Anne W. Beaven, MD|
|Principal Investigator:||Anne W. Beaven, MD||Duke University|