Ibrutinib and Lenalidomide With Dose Adjusted EPOCH-R in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma
- Conditions
- Diffuse Large B Cell Lymphoma RelapsedDiffuse Large B Cell Lymphoma Refractory
- Interventions
- Registration Number
- NCT02142049
- Lead Sponsor
- Pharmacyclics LLC.
- Brief Summary
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).
- Detailed Description
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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
Not provided
- Known central nervous system lymphoma
- Any chemotherapy, external beam radiation therapy, or anti-cancer antibodies within 2 weeks
- Radio- or toxin-immunoconjugates within 10 weeks
- Prior allogenetic stem cell (or other organ) transplant within 6 months or any evidence of active graft-versus-host disease or requirement for immunosuppressants within 28 days prior to first dose of study drug
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: Dose Level 4 Ibrutinib Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R Part 1: Dose Level 1 DA-EPOCH-R Ibrutinib 560 mg PO + DA-EPOCH-R Part 1: Dose Level 2 Ibrutinib Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R Part 1: Dose Level 2 DA-EPOCH-R Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R Part 1: Dose Level 1 Ibrutinib Ibrutinib 560 mg PO + DA-EPOCH-R Part 1: Dose Level 2 Lenalidomide Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R Part 1: Dose Level 3 DA-EPOCH-R Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R Part 1: Dose Level 4 DA-EPOCH-R Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R Part 2: RP2D Ibrutinib Recommended Phase 2 Dose(RP2D): Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R Part 2: RP2D Lenalidomide Recommended Phase 2 Dose(RP2D): Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R Part 2: RP2D DA-EPOCH-R Recommended Phase 2 Dose(RP2D): Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R Part 1: Dose Level 3 Ibrutinib Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R Part 1: Dose Level 3 Lenalidomide Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R Part 1: Dose Level 4 Lenalidomide Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
- Primary Outcome Measures
Name Time Method Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability 1 year after last subjects received the first dose Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R
Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR 1 year after last subjects received the first dose 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.
- Secondary Outcome Measures
Name Time Method Number of Subjects With Adverse Events as a Measure of Safety and Tolerability 1 year after last subjects received the first dose Part 2: The frequency (number and percentage) of treatment-emergent adverse events will be reported.
Duration of Response (DOR) 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. 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.
Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy 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. 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.
Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy 1 year after last subjects received the first dose 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.
Trial Locations
- Locations (10)
SITE-1
🇺🇸Duarte, California, United States
SITE-10
🇺🇸Orange, California, United States
SITE-6
🇺🇸Bethesda, Maryland, United States
SITE-4
🇺🇸Ann Arbor, Michigan, United States
SITE-8
🇺🇸Albuquerque, New Mexico, United States
SITE-7
🇺🇸Charleston, South Carolina, United States
SITE-2
🇺🇸Los Angeles, California, United States
SITE-3
🇺🇸Chicago, Illinois, United States
SITE-5
🇺🇸Baltimore, Maryland, United States
SITE-9
🇺🇸Stony Brook, New York, United States