Safety and Activity of SNX-5422 Plus Ibrutinib in CLL
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Open-label Study of SNX‑5422 and Ibrutinib in Chronic Lymphocytic Leukemia Subjects With a Mutation in Bruton's Tyrosine Kinase|
- Efficacy of the combination of SNX-5422 and ibrutinib [ Time Frame: Every 12 weeks up to 52 weeks ] [ Designated as safety issue: No ]Change in percent of mutated BTK in CLL cells
- Number of subjects reporting adverse events [ Time Frame: Day 28 of each 4 week cycle from randomization up to 52 weeks ] [ Designated as safety issue: Yes ]Frequency and severity of adverse events
- Time to disease progression [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]Elapsed time for each subject from randomization to relapse of disease up to 52 weeks
- Clinical Laboratory testing [ Time Frame: Day 28 of each 4 week cycle from randomization up to 52 weeks ] [ Designated as safety issue: Yes ]Absolute values and changes from baseline for each subject using standard clinical chemistry, hematology and urinalysis parameters
- Electrocardiogram [ Time Frame: Pre-dose on Day 1 of each 4 week cycle from randomization up to 52 weeks ] [ Designated as safety issue: Yes ]Digital 12-lead ECG using standard recording methods at trough drug levels. All ECG recordings will be analyzed for PR, RR, QT intervals, and for morphology.
|Study Start Date:||October 2016|
|Estimated Study Completion Date:||January 2018|
|Estimated Primary Completion Date:||October 2017 (Final data collection date for primary outcome measure)|
Experimental: SNX-5422 plus ibrutinib
Open-label administration of SNX-5422 capsules dosed in the morning once every other day for 21 days (11 doses) followed by a 7 day drug free period and daily with the established ibrutinib dose for 28 days of a 28-days cycle. Subjects will repeat the 28-day schedule until the cancer progresses or the subject is unable to tolerate the therapy
Drug: SNX-5422 plus ibrutinib
SNX-5422 capsule(s) dosed every other day for 21 days out of a 28-day treatment cycle to a total dose of 56 mg/m2 SNX-5422. Subjects will self-administer daily oral ibrutinib in the afternoon at least 8 hours apart from SNX-5422 for 28 days of each cycle.
Other Name: Imbruvica
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults and is not considered curable outside of allogeneic stem cell transplantation.
BTK is a critical kinase in the B cell receptor signaling pathway. This pathway is amplified in CLL and results in amplification of proliferation and anti-apoptotic signals. By inhibiting BTK, ibrutinib eliminates the activation of these pro-survival pathways and microenvironment survival signals. While response to ibrutinib has been high with therapy well-tolerated overall, some patients have relapsed while others have been taken off therapy for toxicity or other reasons. Relapse in CLL can be mediated by at least two separate mechanisms. One is by mutations in BTK, which both decrease ibrutinib's affinity for BTK, and also changes the binding from irreversible to reversible. This is a proof of concept study to investigate whether the addition of SNX-5422 to an established dose of ibrutinib will reduce mutated BTK from CLL cells and/or prevents or delays disease progression of subjects with CLL.
This is an open-label study of SNX‑5422 combined with ibrutinib. In each 28 day cycle, SNX‑5422 will be dosed in the morning once every other day for 21 days, followed by a 7‑day drug‑free period. Subjects will continue to receive daily oral ibrutinib at their established dose level in the afternoon every day for 28 days. cycle
Please refer to this study by its ClinicalTrials.gov identifier: NCT02914327
|Contact: Eric Orlemans, PhDemail@example.com|
|United States, Ohio|
|Wexner Medical Center, Ohio State University||Not yet recruiting|
|Columbus, Ohio, United States, 43210|
|Principal Investigator: Jennifer A Woyach, MD|