This is a Phase 1b/2, open-label, non-randomized multicenter study to assess the safety and efficacy of ibrutinib and lenalidomide in combination with DA-EPOCH-R in subjects with relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL).
This is a Phase 1b, open-label, non-randomized multicenter study conducted in 2 parts. Part 1, will determine the MTD of the combination of ibrutinib, lenalidomide and DA-EPOCH-R in subjects with DLBCL. Ibrutinib will be administered at a fixed dose of 560 mg and lenalidomide will be dose-escalated. DA-EPOCH-R will be given at standard doses. For Part 2, the MTD determined in Part 1 will be the dose used for all subjects. If no MTD is identified, then subjects in Part 2 will be treated with the maximum administered doses (MAD, treatment doses from dose Level 4). The primary objective for Part 2 is to determine the ORR of ibrutinib and lenalidomide in combination with DA-EPOCH-R in subjects with ABC DLBCL as analyzed by gene expression profiling when treated at recommended phase 2 dose (RP2D).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Ibrutinib
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
Lenalidomide
SITE-1
Duarte, California, United States
SITE-2
Los Angeles, California, United States
SITE-10
Orange, California, United States
SITE-3
Chicago, Illinois, United States
Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability
Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R
Time frame: 1 year after last subjects received the first dose
Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR
Part 2 - Overall Response rate will be defined as the proportion of subjects who achieve either a Complete Response or a Partial Response according to the international Working Group Response Criteria for NHL as assessed by investigator.
Time frame: 1 year after last subjects received the first dose
Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy
Part-1: Overall Response rate (ORR) will defined as the proportion of subjects who achieve either a CR or a PR according to the international Working Group Response Criteria for NHL as assessed by investigator.
Time frame: 1 year after last subjects received the first dose
Number of Subjects With Adverse Events as a Measure of Safety and Tolerability
Part 2: The frequency (number and percentage) of treatment-emergent adverse events will be reported.
Time frame: 1 year after last subjects received the first dose
Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy
Part 2: PFS will be measured as time from first study drug administration to disease progression or death from any cause. OS will be measured from the time of first study drug administration until the date of death using Kaplan-Meier methodology.
Time frame: From initial dose date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose, up to 36 months at the most.
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SITE-5
Baltimore, Maryland, United States
SITE-6
Bethesda, Maryland, United States
SITE-4
Ann Arbor, Michigan, United States
SITE-8
Albuquerque, New Mexico, United States
SITE-9
Stony Brook, New York, United States
SITE-7
Charleston, South Carolina, United States
Duration of Response (DOR)
Part 2: DOR will be measured from the time by which the measurement criteria are met for CR or PR until the first date by which recurrent or progressive disease is objectively documented.
Time frame: From initial response date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose.